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"REDUCE" - A Clinical Research Study To Reduce The Incidence Of Prostate Cancer In Men Who Are At Increased Risk (REDUCE)

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ClinicalTrials.gov Identifier: NCT00056407
Recruitment Status : Completed
First Posted : March 13, 2003
Results First Posted : March 5, 2010
Last Update Posted : September 23, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Neoplasms, Prostate
Interventions Drug: Dutasteride
Drug: Placebo
Enrollment 8231
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules. Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Period Title: Overall Study
Started 4126 4105
Completed 2915 2912
Not Completed 1211 1193
Reason Not Completed
Adverse Event             282             364
Withdrawal by Subject             377             361
Lost to Follow-up             123             113
Protocol Violation             104             95
Diagnosed with Prostate Cancer             202             166
Listed as "Other" on Case Report Form             98             60
Missing             25             34
Arm/Group Title Placebo Dutasteride 0.5 mg Total
Hide Arm/Group Description Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules. Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule. Total of all reporting groups
Overall Number of Baseline Participants 4126 4105 8231
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4126 participants 4105 participants 8231 participants
62.7  (6.08) 62.8  (6.04) 62.8  (6.06)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4126 participants 4105 participants 8231 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
4126
 100.0%
4105
 100.0%
8231
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 4126 participants 4105 participants 8231 participants
White 3747 3744 7491
Black 99 91 190
Asian 67 67 134
American Hispanic 173 160 333
Other 39 43 82
Missing 1 0 1
1.Primary Outcome
Title Number of Participants With Biopsy-detectable Prostate Cancer at Years 2 and 4 (Crude Rate Approach)
Hide Description Study biopsies consisted of 10 biopsy samples (cores) in a pre-defined pattern. Biopsies were read at the central pathology laboratory (CPL, which processed the majority, 94%, of biopsies). Biopsy cases that were positive for prostate cancer or precancerous lesions (high-grade prostatic intraepithelial neoplasia[HGPIN] or typical small acinar proliferation [ASAP]) and prostate surgeries were reviewed by the lead pathologist.
Time Frame Years 1-2, Years 3-4, and Overall (Years 1-4)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all randomized participants with a negative entry biopsy, as determined by the CPL, who received at least 1 dose of study drug. The crude rate approach included all participants at risk at the beginning of each time period .
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
Years 1- 2, n=4073, 4049 578 435
Years 3- 4, n=2815, 2844 280 224
Overall, n=4073, 4049 858 659
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p value is given is for the overall assessment.
Method Mantel-Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk Reduction
Estimated Value 23.3
Confidence Interval 95%
15.6 to 30.3
Estimation Comments Estimation data given are for the overall assessment.
2.Primary Outcome
Title Number of Participants With Biopsy-detectable Prostate Cancer at Years 2 and 4 (Modified Crude Rate Approach)
Hide Description Study biopsies (biop.) consisted of 10 biop. samples (cores) in a pre-defined pattern and were read at the central pathology laboratory. Biop. cases that were positive for prostate cancer or precancerous lesions (HGPIN or ASAP) and prostate surgeries were reviewed by the lead pathologist. Participants included in the risk sets at Years 1-2 and Years 3-4 included those with a positive biop. at Years 1-2 or a biop. after Months 18-24, and those with a positive biop. at Years 3-4 or a biop. after Month 42, respectively. Overall included participants with a positive biop. or biop. after Month 42.
Time Frame Years 1-2, Years 3-4, and Overall (Years 1-4)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population, modified crude rate: participants who either were diagnosed with prostate cancer during the study or had an end of time period biopsy. N for each time period is the number who either had at least 1 biopsy in the final 6 months of the time period or had a positive biopsy anytime during the time period.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3319 3209
Measure Type: Number
Unit of Measure: participants
Years 1-2, n=3319, 3209 578 435
Years 3-4, n=2325, 2434 280 224
Overall, n=2903, 2869 858 659
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p value is given is for the overall assessment.
Method Mantel-Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk Reduction
Estimated Value 23.1
Confidence Interval 95%
15.5 to 30.0
Estimation Comments Estimation data are given are for the overall assessment.
3.Primary Outcome
Title Number of Participants With Biopsy-detectable Prostate Cancer at Years 2 and 4 (Restricted Crude Rate Approach)
Hide Description Study biopsies consisted of 10 biopsy samples (cores) in a pre-defined pattern. Biopsies were read at the central pathology laboratory (which processed the majority, 94%, of biopsies). Biopsy cases that were positive for prostate cancer or precancerous lesions (HGPIN or ASAP) and prostate surgeries were reviewed by the lead pathologist. Participants included in the risk set at Years 1-2, Years 3-4, and Overall (Years 1-4) were those who had a biopsy during the specified time period.
Time Frame Years 1-2, Years 3-4, and Overall (Years 1-4)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population, restricted crude rate: the number of prostate cancer events is based on the the number of participants who had at least one biopsy during the time period. Ns at Years 1-2 and Years 3-4 are the number who had a biopsy in those time periods; the overall n is the number of participants who had 1 or more biopsy during Years 1-4.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3424 3305
Measure Type: Number
Unit of Measure: participants
Years 1-2, n=3364, 3244 578 435
Years 3- 4, n=2359, 2451 280 224
Overall, n=3424, 3305 858 659
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p value is given for the overall assessment.
Method Mantel-Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk Reduction
Estimated Value 22.8
Confidence Interval 95%
15.2 to 29.8
Estimation Comments Estimation data are given for the overall assessment.
4.Secondary Outcome
Title Number of Participants With the Indicated Gleason Score at Diagnosis
Hide Description Gleason score was determined by examining prostate biopsies and surgical samples. The Gleason scoring system sums the two most common Gleason grade patterns in order to predict the likelihood of a participant doing well or badly with their cancer. Gleason grades range from 1 (normal) to 5 (advanced cancer). The lowest Gleason score is 2 (1+1), and the highest Gleason score is 10 (5+5). A Gleason score of 2-6 is a low-grade cancer; a Gleason score of 7-10 is high-grade cancer. The most severe high-grade cancers are the subset of Gleason scores 8-10.
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Biopsied Population: all randomized participants with a negative entry biopsy who received at least 1 dose of study treatment and who had at least 1 biopsy reviewed by the central pathology lab. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3407 3299
Measure Type: Number
Unit of Measure: participants
Between 2 and 6 617 437
Between 7 and 10 233 220
Between 8 and 10 19 29
5.Secondary Outcome
Title Number of Participants With HGPIN, ASAP, and Prostate Cancer at Biopsy
Hide Description The occurrence and quantity of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) at biopsy were measured. HGPIN and ASAP are considered precancerous conditions. A participant diagnosed with prostate cancer only (i.e., no HGPIN or ASAP) was counted in both the first category ("HGPIN or prostate cancer diagnosis") and again in the last category ("HGPIN, ASAP, or prostate cancer diagnosis").
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Biopsied Population: the number analyzed is the total number in the population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3424 3305
Measure Type: Number
Unit of Measure: participants
HGPIN or prostate cancer diagnosis 1126 810
HGPIN and no prostate cancer 268 151
HGPIN and no ASAP and no prostate cancer 206 121
HGPIN or ASAP 675 409
HGPIN or ASAP and no prostate cancer 373 248
HGPIN, ASAP, or prostate cancer diagnosis 1231 907
6.Secondary Outcome
Title Volume of HGPIN at Biopsy
Hide Description The amount of prostate biopsy tissue with HGPIN was measured.
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Biopsied Population. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3403 3297
Mean (Standard Deviation)
Unit of Measure: cc*10^-3 (microliter)
0.1105  (0.52753) 0.0446  (0.2771)
7.Secondary Outcome
Title Percentage of Core Involved at Diagnosis
Hide Description The average amount of cancer seen by the pathologist in the prostate tissue samples taken during the biopsy was measured. A core is a prostate biopsy sample.
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Prostate Cancer Population: all participants in the Efficacy Population who received a post-baseline diagnosis of prostate cancer by the central pathology laboratory. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 849 657
Mean (Standard Deviation)
Unit of Measure: percentage of core
13.4  (14.84) 12.2  (13.00)
8.Secondary Outcome
Title Number of Cancer-positive Cores
Hide Description The average number of prostate biopsy samples (cores) determined to be cancerous by the pathologist was measured. Normally, 10 cores were taken per biopsy for each participant.
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Prostate Cancer Population. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 850 656
Mean (Standard Deviation)
Unit of Measure: number of cores
1.9  (1.31) 1.8  (1.33)
9.Secondary Outcome
Title Treatment Alteration Score
Hide Description The treatment alteration score is a measure of the cellular changes due to treatment (effect of male hormone withdrawal) on the nucleus and cytoplasm of the prostate cancer cell. The treatment alteration score is the sum of two scores (the nuclear alteration score and the cytoplasmic architectural score), each ranging from 0 to 3, with 0 indicating no change and 3 indicating severe changes.
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Biopsied Population. Only needle biopsies are included (surgeries are excluded). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3357 3258
Mean (Standard Deviation)
Unit of Measure: points on a scale
Nuclear, n=3357, 3256 0.008  (0.1116) 0.019  (0.1734)
Architectural, n=3357, 3258 0.009  (0.1289) 0.023  (0.2112)
Total, n=3357, 3256 0.017  (0.2336) 0.041  (0.3737)
10.Secondary Outcome
Title Number of Participants Undergoing Intervention (Surgical and Non-surgical) for Prostate Cancer Treatment
Hide Description The number of participants who received treatment for prostate cancer was measured. Prostate cancer interventions included surgical interventions (e.g., prostatectomy, adenomectomy, transurethral resection) and non-surgical interventions (e.g., chemotherapy, hormone therapy, radiation therapy).
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
Any intervention 438 300
Any surgical intervention 304 221
Any non-surgical intervention 172 95
11.Secondary Outcome
Title Adjusted Mean Change From Baseline in the International Prostate Symptom Score (IPSS) at Month 48
Hide Description The IPSS is a 7-item questionnaire that measures urinary symptoms. It measures the level of urinary symptoms (including incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) reported as the total IPSS score. Each of the 7 questions has a 6-point response scale (0=none/not at all to 5=almost always) with a total score that can range from 0-35: mild (0-7), moderate (8-19), or severe (20-35). Estimates are based on adjusted means from the general linear model: change from baseline = baseline value and cluster and treatment.
Time Frame Baseline to Year 4 (Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population, last observation carried forward (LOCF). In the LOCF approach, missing values at post-baseline assessments are replaced with the participant's previous non-missing post-baseline assessment. The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3847 3815
Mean (Standard Error)
Unit of Measure: points on a scale
1.35  (0.087) -0.46  (0.087)
12.Secondary Outcome
Title Adjusted Mean Percentage Change From Baseline in Prostate Volume at Months 24 and 48
Hide Description Prostate volume was measured by transrectal ultrasound (TRUS) when biopsies were performed at Year 2 and Year 4. The investigator calculated the prostate volume using three prostate measurements (anteroposterior, cephalocaudal, and transverse diameters). Estimates are based on the adjusted means from the general linear model: log(Post-Baseline/Baseline value) = treatment and cluster and log (baseline value).
Time Frame Baseline, Month 24, and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3289 3194
Mean (Standard Error)
Unit of Measure: percent change
Month 24, n=3192, 3116 13.0  (0.65) -17.4  (0.48)
Month 48, n=3289, 3194 19.7  (0.77) -17.5  (0.54)
13.Secondary Outcome
Title Adjusted Mean Change From Baseline in Maximum Urinary Flow (Qmax) at Months 12, 24, 36, and 48
Hide Description Maximum urinary flow was measured at selected sites using a Dantec Uroflow meter with a Thompson filter. Change from baseline was calculated as Month 12, 24, 36, and 48 values minus the baseline value. Estimates are based on the adjusted means from the general linear model: change from baseline = baseline Qmax and treatment. This measurement was performed at selected centers.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 1390 1359
Mean (Standard Error)
Unit of Measure: milliliters/second
Month 12, n=1178, 1168 -0.55  (0.253) 0.27  (0.255)
Month 24, n=1337, 1295 -0.63  (0.410) 0.60  (0.416)
Month 36, n=1375, 1334 -0.74  (0.238) 0.13  (0.241)
Month 48, n=1390, 1359 -0.90  (0.303) 0.41  (0.307)
14.Secondary Outcome
Title Number of Participants Starting Alpha Blockers to Control Benign Prostatic Hyperplasia (BPH) Symptoms
Hide Description Medication taken during the study, including alpha blockers, was recorded at each 6-month study visit and during phone calls that occurred 3 months after each visit.
Time Frame Years 1-2, Overall (Years 1-4)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
Years 1-2 425 317
Overall 770 515
15.Secondary Outcome
Title Number of Participants With at Least One Event of Acute Urinary Retention (AUR)
Hide Description A participant was considered to have AUR when he reported being unable to urinate and required catherization. Participants were asked to report any events of AUR during the study.
Time Frame Years 1-2 and Overall (Years 1-4)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
Years 1-2 150 39
Overall 272 63
16.Secondary Outcome
Title Number of Participants With at Least One Urinary Tract Infection (UTI)
Hide Description A participant was considered to have a UTI if the investigator noted that the participant had UTI symptoms and had been prescribed antibiotics. Participants were asked to report any events of UTI during the study.
Time Frame Years 1-2, Years 3-4, and Overall (Years 1-4)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
Years 1-2, n=4073, 4049 196 131
Years 3-4, n=3363, 3318 164 83
Overall, n=4073, 4049 360 214
17.Secondary Outcome
Title Number of Participants With Post-biopsy Macroscopic Hematuria
Hide Description Participants reported events of macroscopic hematuria (visible blood in the urine) throughout the study.
Time Frame Baseline to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
168 127
18.Secondary Outcome
Title Number of Participants With Post-biopsy Macroscopic Hematospermia
Hide Description Participants reported events of macroscopic hematospermia (visible blood in semen) throughout the study.
Time Frame Baseline through Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: participants
78 53
19.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is assessed as the number of deaths reported throughout the study.
Time Frame From time informed consent is signed to 4-month Safety Follow-Up period
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 4073 4049
Measure Type: Number
Unit of Measure: number of deaths
Years 1-2 29 32
Overall 77 70
20.Secondary Outcome
Title Adjusted Mean Change From Baseline in the Benign Prostatic Hypertrophy (BPH) Impact Index (BII) at Month 48
Hide Description The BII is a 4-item questionnaire that rates the level of BPH-related physical discomfort, worry, and interference with normal activities the participant has experienced. The total BII score ranges from 1 (no impact on symptoms) to 13 (major impact on symptoms). Participants completed the questionnaire at Baseline and at each 6-month visit. Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model:change from baseline = baseline value and cluster and treatment.
Time Frame Baseline and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The numbers presented are less than the overall population, as data were not available for all participants.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3733 3727
Mean (Standard Error)
Unit of Measure: points on a scale
0.44  (0.037) -0.21  (0.037)
21.Secondary Outcome
Title Adjusted Mean Change From Baseline in The Medical Outcomes Study Sleep Problems Index 6-item Standard Version (MOS Sleep-6S) at Month 48
Hide Description The MOS Sleep-6S is a 6-item questionnaire measuring quality of sleep. Scores range from 1 (all of the time) to 6 (none of the time) and are converted to a 1-100 scale and then averaged; a higher score indicates greater negative impact, which indicates more sleep disturbance. Participants completed the questionnaire at Baseline and at each 6-month visit. Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model: change from baseline=baseline value and cluster and treatment.
Time Frame Baseline and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The numbers presented are less than the overall population, as data were not available for all participants.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3726 3709
Mean (Standard Error)
Unit of Measure: points on a scale
-0.03  (0.211) 0.02  (0.212)
22.Secondary Outcome
Title Adjusted Mean Change From Baseline in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH CPSI) at Month 48
Hide Description The NIH CSPI is a 9-item questionnaire that measures chronic prostatitis symptoms. The total score ranges from 0 to 43. A higher score indicates greater negative impact of prostatitis. Participants completed the questionnaire at Baseline and at each 6-month visit. Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model: change from Baseline = Baseline Value and Cluster and Treatment.
Time Frame Baseline and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The numbers presented are less than the overall population, as data were not available for all participants.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 2576 2590
Mean (Standard Error)
Unit of Measure: points on a scale
0.94  (0.123) -0.37  (0.123)
23.Secondary Outcome
Title Adjusted Mean Change From Baseline in Quality of Life Question 8 (QOL Q8) at Month 48
Hide Description The QOL Q8 is the last question of the IPSS Questionnaire. It is a question about the participant's quality of life as it relates to prostate symptoms. Responses range from 0 (most positive) to 6 (most negative). A higher score indicates worse quality of life. Participants completed the questionnaire at Screening, Baseline, and at each 6-month visit. Estimates are based on the adjusted means from the general linear model: change from baseline = baseline value and cluster and treatment.
Time Frame Baseline and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3853 3821
Mean (Standard Error)
Unit of Measure: points on a scale
-0.06  (0.018) -0.33  (0.018)
24.Secondary Outcome
Title Adjusted Mean Change From Baseline in the Problem Assessment Scale of the Sexual Function Index (PASSFI) at Month 48
Hide Description The PASSFI is a 3-item questionnaire that measures sexual function. Responses range from 0 (big problem) to 4 (no problem), with a total score of 12. A higher score indicates fewer problems with sexual functioning. Participants completed the questionnaire at Baseline and then yearly . Participants whose language did not have a validated translation of the questionnaire did not participate. Estimates are based on the adjusted means from the general linear model: change from baseline = baseline value and cluster and treatment.
Time Frame Baseline and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3413 3329
Mean (Standard Error)
Unit of Measure: points on a scale
-0.82  (0.064) -1.5  (0.065)
25.Secondary Outcome
Title Number of Participants With the Indicated Serum Dihydrotestosterone (DHT) Concentration at Month 48
Hide Description Number of participants whose DHT, the active form of the male sex hormone testosterone, was less than 0.555 nanomoles/liter and below the level of detection at Month 48 was measured. It was measured by taking blood samples at screening and yearly thereafter.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The number analyzed is smaller than the total number in the population due to missing values.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3865 3822
Measure Type: Number
Unit of Measure: participants
<0.555 nanomoles/Liter 493 3414
<level of detection 42 2210
26.Secondary Outcome
Title Mean Change From Baseline in Testosterone at Month 48
Hide Description Testosterone, a male sex hormone, was measured by taking blood samples at screening and yearly thereafter.
Time Frame Baseline and Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population (LOCF). The numbers presented are less than the overall population, as data were not available for all participants.
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description:
Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules.
Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
Overall Number of Participants Analyzed 3841 3796
Mean (Standard Deviation)
Unit of Measure: percent change
-0.1  (36.95) 20.0  (44.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method general linear model, t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted means
Estimated Value 18.8
Confidence Interval 95%
17.3 to 20.4
Estimation Comments The adjusted mean difference was calculated as the difference between the adjusted means (-6.1 and 12.7) for the placebo and Dutasteride arms, respectively.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Dutasteride 0.5 mg
Hide Arm/Group Description Placebo, repeat oral once daily dosing for 4 years. Placebo supplied as matching dutasteride capsules. Dutasteride 0.5 milligrams (mg), repeat oral once daily dosing for 4 years. Dutasteride supplied as gelatin capsule.
All-Cause Mortality
Placebo Dutasteride 0.5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Dutasteride 0.5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   837/4126 (20.29%)   748/4105 (18.22%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  3/4126 (0.07%)  2/4105 (0.05%) 
Lymphadenopathy  1  1/4126 (0.02%)  3/4105 (0.07%) 
Thrombocytopenia  1  0/4126 (0.00%)  4/4105 (0.10%) 
Anaemia  1  0/4126 (0.00%)  2/4105 (0.05%) 
Febrile neutropenia  1  1/4126 (0.02%)  1/4105 (0.02%) 
Leukopenia  1  0/4126 (0.00%)  2/4105 (0.05%) 
Microcytic anaemia  1  0/4126 (0.00%)  2/4105 (0.05%) 
Splenomegaly  1  0/4126 (0.00%)  2/4105 (0.05%) 
Leukocytosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Splenic haemorrhage  1  0/4126 (0.00%)  1/4105 (0.02%) 
Autoimmune thrombocytopenia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Blood disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cardiac disorders     
Acute coronary syndrome  1  4/4126 (0.10%)  2/4105 (0.05%) 
Acute myocardial infarction  1  9/4126 (0.22%)  9/4105 (0.22%) 
Angina pectoris  1  35/4126 (0.85%)  14/4105 (0.34%) 
Angina unstable  1  7/4126 (0.17%)  9/4105 (0.22%) 
Aortic valve disease  1  1/4126 (0.02%)  2/4105 (0.05%) 
Aortic valve incompetence  1  1/4126 (0.02%)  1/4105 (0.02%) 
Aortic valve stenosis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Arrhythmia  1  16/4126 (0.39%)  6/4105 (0.15%) 
Arteriosclerosis coronary artery  1  2/4126 (0.05%)  3/4105 (0.07%) 
Atrial fibrillation  1  21/4126 (0.51%)  18/4105 (0.44%) 
Atrial flutter  1  7/4126 (0.17%)  2/4105 (0.05%) 
Atrial tachycardia  1  2/4126 (0.05%)  0/4105 (0.00%) 
Atrioventricular block  1  3/4126 (0.07%)  0/4105 (0.00%) 
Atrioventricular block complete  1  1/4126 (0.02%)  1/4105 (0.02%) 
Atrioventricular block second degree  1  2/4126 (0.05%)  0/4105 (0.00%) 
Bradycardia  1  1/4126 (0.02%)  1/4105 (0.02%) 
Cardiac arrest  1  6/4126 (0.15%)  1/4105 (0.02%) 
Cardiac disorder  1  2/4126 (0.05%)  0/4105 (0.00%) 
Cardiac failure  1  4/4126 (0.10%)  12/4105 (0.29%) 
Cardiac failure acute  1  1/4126 (0.02%)  3/4105 (0.07%) 
Cardiac failure chronic  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cardiac failure congestive  1  4/4126 (0.10%)  7/4105 (0.17%) 
Cardiac tamponade  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cardiac valve disease  1  1/4126 (0.02%)  4/4105 (0.10%) 
Cardio-respiratory arrest  1  1/4126 (0.02%)  1/4105 (0.02%) 
Cardiogenic shock  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cardiomyopathy  1  3/4126 (0.07%)  0/4105 (0.00%) 
Cardiopulmonary failure  1  0/4126 (0.00%)  1/4105 (0.02%) 
Congestive cardiomyopathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Coronary artery disease  1  23/4126 (0.56%)  36/4105 (0.88%) 
Coronary artery occlusion  1  5/4126 (0.12%)  4/4105 (0.10%) 
Coronary artery stenosis  1  10/4126 (0.24%)  8/4105 (0.19%) 
Coronary artery thrombosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Diastolic dysfunction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hypertrophic cardiomyopathy  1  1/4126 (0.02%)  1/4105 (0.02%) 
Ischaemic cardiomyopathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Left ventricular dysfunction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Left ventricular failure  1  1/4126 (0.02%)  0/4105 (0.00%) 
Mitral valve incompetence  1  1/4126 (0.02%)  2/4105 (0.05%) 
Mitral valve prolapse  1  0/4126 (0.00%)  1/4105 (0.02%) 
Myocardial infarction  1  43/4126 (1.04%)  38/4105 (0.93%) 
Myocardial ischaemia  1  5/4126 (0.12%)  7/4105 (0.17%) 
Pericardial effusion  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pericarditits  1  3/4126 (0.07%)  2/4105 (0.05%) 
Postinfarction angina  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pulmonary valve stenosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Sinoatrial block  1  0/4126 (0.00%)  1/4105 (0.02%) 
Sinus bradycardia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Supraventricular tachycardia  1  3/4126 (0.07%)  1/4105 (0.02%) 
Tachyarrhythmia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Tachycardia  1  4/4126 (0.10%)  1/4105 (0.02%) 
Ventricle rupture  1  0/4126 (0.00%)  1/4105 (0.02%) 
Ventricular arrhythmia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Ventricular extrasystoles  1  1/4126 (0.02%)  2/4105 (0.05%) 
Ventricular fibrillation  1  1/4126 (0.02%)  0/4105 (0.00%) 
Ventricular tachycardia  1  1/4126 (0.02%)  2/4105 (0.05%) 
Congenital, familial and genetic disorders     
Hydrocele  1  4/4126 (0.10%)  4/4105 (0.10%) 
Phimosis  1  2/4126 (0.05%)  2/4105 (0.05%) 
Hip dysplasia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Ear and labyrinth disorders     
Vertigo  1  2/4126 (0.05%)  6/4105 (0.15%) 
Labyrinthine fistula  1  0/4126 (0.00%)  1/4105 (0.02%) 
Vestibular ataxia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Deafness unilateral  1  0/4126 (0.00%)  1/4105 (0.02%) 
Sudden hearing loss  1  1/4126 (0.02%)  0/4105 (0.00%) 
Neurosensory hypoacusis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Endocrine disorders     
Goitre  1  3/4126 (0.07%)  0/4105 (0.00%) 
Hyperthyroidism  1  2/4126 (0.05%)  1/4105 (0.02%) 
Cushing's Syndrome  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hyperparathyroidism primary  1  1/4126 (0.02%)  0/4105 (0.00%) 
Eye disorders     
Retinal detachment  1  4/4126 (0.10%)  6/4105 (0.15%) 
Glaucoma  1  3/4126 (0.07%)  0/4105 (0.00%) 
Cataract  1  0/4126 (0.00%)  2/4105 (0.05%) 
Retinal haemorrhage  1  1/4126 (0.02%)  1/4105 (0.02%) 
Retinal vein thrombosis  1  2/4126 (0.05%)  0/4105 (0.00%) 
Blindness  1  1/4126 (0.02%)  0/4105 (0.00%) 
Corneal opacity  1  1/4126 (0.02%)  0/4105 (0.00%) 
Maculopathy  1  0/4126 (0.00%)  1/4105 (0.02%) 
Myopia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Optic ischaemic neuropathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Retinal ischaemia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Retinal tear  1  0/4126 (0.00%)  1/4105 (0.02%) 
Retinal vein occlusion  1  0/4126 (0.00%)  1/4105 (0.02%) 
Dacryostenosis acquired  1  1/4126 (0.02%)  0/4105 (0.00%) 
Retinoschisis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gastrointestinal disorders     
Abdominal hernia  1  2/4126 (0.05%)  1/4105 (0.02%) 
Abdominal pain  1  3/4126 (0.07%)  2/4105 (0.05%) 
Abdominal pain upper  1  0/4126 (0.00%)  2/4105 (0.05%) 
Abdominal strangulated hernia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Anal fistula  1  1/4126 (0.02%)  1/4105 (0.02%) 
Ascites  1  1/4126 (0.02%)  0/4105 (0.00%) 
Colitis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Colitis ulcerative  1  0/4126 (0.00%)  1/4105 (0.02%) 
Colonic polyp  1  2/4126 (0.05%)  6/4105 (0.15%) 
Constipation  1  4/4126 (0.10%)  0/4105 (0.00%) 
Diarrhea  1  2/4126 (0.05%)  2/4105 (0.05%) 
Diverticular perforation  1  1/4126 (0.02%)  0/4105 (0.00%) 
Diverticulum  1  2/4126 (0.05%)  1/4105 (0.02%) 
Diverticulum intestinal  1  0/4126 (0.00%)  1/4105 (0.02%) 
Duodenal ulcer  1  2/4126 (0.05%)  2/4105 (0.05%) 
Duodenal ulcer haemorrhage  1  0/4126 (0.00%)  1/4105 (0.02%) 
Duodenal ulcer perforation  1  0/4126 (0.00%)  1/4105 (0.02%) 
Dysphagia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Food poisoning  1  0/4126 (0.00%)  1/4105 (0.02%) 
Gastric disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Gastric haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gastric ulcer  1  1/4126 (0.02%)  5/4105 (0.12%) 
Gastric ulcer haemorrhage  1  1/4126 (0.02%)  1/4105 (0.02%) 
Gastritis  1  4/4126 (0.10%)  9/4105 (0.22%) 
Gastritis haemorrhagic  1  1/4126 (0.02%)  1/4105 (0.02%) 
Gastrointestinal dysplasia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Gastrointestinal ulcer haemorrhage  1  0/4126 (0.00%)  1/4105 (0.02%) 
Gastrooesophageal reflux disease  1  1/4126 (0.02%)  2/4105 (0.05%) 
Haematemesis  1  0/4126 (0.00%)  4/4105 (0.10%) 
Haemorrhoids  1  2/4126 (0.05%)  2/4105 (0.05%) 
Hiatus hernia  1  2/4126 (0.05%)  1/4105 (0.02%) 
Ileus  1  1/4126 (0.02%)  3/4105 (0.07%) 
Ileus paralytic  1  1/4126 (0.02%)  0/4105 (0.00%) 
Inguinal hernia  1  28/4126 (0.68%)  31/4105 (0.76%) 
Inguinal hernia strangulated  1  1/4126 (0.02%)  0/4105 (0.00%) 
Inguinal hernia, obstructive  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intestinal ischaemia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intestinal obstruction  1  3/4126 (0.07%)  0/4105 (0.00%) 
Intestinal perforation  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intra-abdominal haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Large intestinal haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Lower gastrointestinal haemorrhage  1  1/4126 (0.02%)  1/4105 (0.02%) 
Mechanical ileus  1  0/4126 (0.00%)  1/4105 (0.02%) 
Melaena  1  1/4126 (0.02%)  0/4105 (0.00%) 
Nausea  1  1/4126 (0.02%)  1/4105 (0.02%) 
Oesophageal pain  1  0/4126 (0.00%)  1/4105 (0.02%) 
Oesophageal stenosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Oesophageal ulcer  1  1/4126 (0.02%)  1/4105 (0.02%) 
Oesophageal varices haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Oesophagitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pancreatitis acute  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pancreatic disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pancreatitis  1  4/4126 (0.10%)  3/4105 (0.07%) 
Peptic ulcer haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Peritonitis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Pharyngoesophageal diverticulm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Polyp colorectal  1  1/4126 (0.02%)  0/4105 (0.00%) 
Proctocolitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Rectal haemorrhage  1  6/4126 (0.15%)  4/4105 (0.10%) 
Reflux oesophagitis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Retroperitoneal haemorrhage  1  0/4126 (0.00%)  1/4105 (0.02%) 
Sigmoiditis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Small intestinal haemorrhage  1  0/4126 (0.00%)  1/4105 (0.02%) 
Small intestinal obstruction  1  4/4126 (0.10%)  2/4105 (0.05%) 
Small intestinal perforation  1  0/4126 (0.00%)  2/4105 (0.05%) 
Umbilical hernia  1  3/4126 (0.07%)  2/4105 (0.05%) 
Umbilical hernia, obstructive  1  1/4126 (0.02%)  0/4105 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/4126 (0.00%)  3/4105 (0.07%) 
Vomiting  1  3/4126 (0.07%)  0/4105 (0.00%) 
Gastrointestinal haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
General disorders     
Chest pain  1  6/4126 (0.15%)  3/4105 (0.07%) 
Non-cardiac chest pain  1  4/4126 (0.10%)  4/4105 (0.10%) 
Pyrexia  1  3/4126 (0.07%)  4/4105 (0.10%) 
Death  1  2/4126 (0.05%)  1/4105 (0.02%) 
Odema peripheral  1  2/4126 (0.05%)  1/4105 (0.02%) 
Chest discomfort  1  1/4126 (0.02%)  1/4105 (0.02%) 
Multi-organ failure  1  0/4126 (0.00%)  2/4105 (0.05%) 
General physical health deterioration  1  0/4126 (0.00%)  2/4105 (0.05%) 
Hernia obstructive  1  1/4126 (0.02%)  1/4105 (0.02%) 
Asthenia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Fatigue  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gait disturbance  1  0/4126 (0.00%)  1/4105 (0.02%) 
Sudden death  1  0/4126 (0.00%)  1/4105 (0.02%) 
Polyp  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hepatobiliary disorders     
Cholelithiasis  1  10/4126 (0.24%)  16/4105 (0.39%) 
Cholecystitis  1  6/4126 (0.15%)  6/4105 (0.15%) 
Cholecystitis acute  1  7/4126 (0.17%)  5/4105 (0.12%) 
Cholangitis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Bile duct stone  1  2/4126 (0.05%)  0/4105 (0.00%) 
Biliary colic  1  1/4126 (0.02%)  1/4105 (0.02%) 
Cirrhosis alcoholic  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gallbladder pain  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hepatic function abnormal  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hepatitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hepatitis alcoholic  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hepatomegaly  1  0/4126 (0.00%)  1/4105 (0.02%) 
Jaundice  1  1/4126 (0.02%)  0/4105 (0.00%) 
Jaundice cholestatic  1  0/4126 (0.00%)  1/4105 (0.02%) 
Bile duct obstruction  1  1/4126 (0.02%)  0/4105 (0.00%) 
Biliary tract disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Immune system disorders     
Anaphylactic reaction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Anaphylactic shock  1  0/4126 (0.00%)  1/4105 (0.02%) 
Polyarteritis nodosa  1  0/4126 (0.00%)  1/4105 (0.02%) 
Sarcoidosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Allergy to plants  1  0/4126 (0.00%)  1/4105 (0.02%) 
Infections and infestations     
Abdominal abscess  1  1/4126 (0.02%)  1/4105 (0.02%) 
Abscess  1  1/4126 (0.02%)  0/4105 (0.00%) 
Abscess limb  1  1/4126 (0.02%)  0/4105 (0.00%) 
Acquired immunodeficiency syndrome  1  2/4126 (0.05%)  0/4105 (0.00%) 
Anal abscess  1  1/4126 (0.02%)  0/4105 (0.00%) 
Appendicitis  1  12/4126 (0.29%)  2/4105 (0.05%) 
Arthritis bacterial  1  0/4126 (0.00%)  1/4105 (0.02%) 
Bacteraemia  1  3/4126 (0.07%)  2/4105 (0.05%) 
Brain abscess  1  1/4126 (0.02%)  1/4105 (0.02%) 
Bronchiectasis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bronchitis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Candida sepsis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Catheter site infection  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cellulitis  1  3/4126 (0.07%)  5/4105 (0.12%) 
Cholangitis suppurative  1  1/4126 (0.02%)  1/4105 (0.02%) 
Cholecystitis infective  1  1/4126 (0.02%)  0/4105 (0.00%) 
Chronic sinusitis  1  1/4126 (0.02%)  2/4105 (0.05%) 
Cystitis  1  3/4126 (0.07%)  0/4105 (0.00%) 
Diverticulitis  1  3/4126 (0.07%)  2/4105 (0.05%) 
Empyema  1  1/4126 (0.02%)  1/4105 (0.02%) 
Endocarditis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Endocarditis bacterial  1  1/4126 (0.02%)  0/4105 (0.00%) 
Epstein-Barr virus infection  1  0/4126 (0.00%)  1/4105 (0.02%) 
Erysipelas  1  1/4126 (0.02%)  1/4105 (0.02%) 
Escherichia infection  1  1/4126 (0.02%)  0/4105 (0.00%) 
Escherichia sepsis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Escherichia urinary tract infection  1  2/4126 (0.05%)  0/4105 (0.00%) 
Gastroenteritis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Helicobacter infection  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hepatitis E  1  1/4126 (0.02%)  0/4105 (0.00%) 
Herpes zoster  1  0/4126 (0.00%)  1/4105 (0.02%) 
Infected bites  1  0/4126 (0.00%)  1/4105 (0.02%) 
Infected lymphocele  1  1/4126 (0.02%)  0/4105 (0.00%) 
Infection  1  0/4126 (0.00%)  1/4105 (0.02%) 
Infective exacerbation of chronic obstructive airways disease  1  1/4126 (0.02%)  2/4105 (0.05%) 
Infective tenosynoyitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Influenza  1  1/4126 (0.02%)  0/4105 (0.00%) 
Injection site abscess  1  0/4126 (0.00%)  1/4105 (0.02%) 
Intervertebral discitis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Labyrinthitis  1  3/4126 (0.07%)  0/4105 (0.00%) 
Laryngitis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Lobar pneumonia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Localised infection  1  2/4126 (0.05%)  0/4105 (0.00%) 
Lower respiratory tract infection  1  3/4126 (0.07%)  3/4105 (0.07%) 
Malaria  1  0/4126 (0.00%)  1/4105 (0.02%) 
Meningitis borrelia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Nosocomial infection  1  0/4126 (0.00%)  1/4105 (0.02%) 
Orchitis  1  4/4126 (0.10%)  0/4105 (0.00%) 
Pelvic abscess  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pharyngitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pneumocystis jiroveci pneumonia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pneumonia  1  25/4126 (0.61%)  24/4105 (0.58%) 
Pneumonia primary atypical  1  0/4126 (0.00%)  1/4105 (0.02%) 
Post procedural infection  1  2/4126 (0.05%)  1/4105 (0.02%) 
Post procedural sepsis  1  7/4126 (0.17%)  1/4105 (0.02%) 
Postoperative abscess  1  1/4126 (0.02%)  0/4105 (0.00%) 
Postoperative wound infection  1  4/4126 (0.10%)  1/4105 (0.02%) 
Prostate infection  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pyelonephritis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Pyelonephritis acute  1  1/4126 (0.02%)  0/4105 (0.00%) 
Respiratory tract infection  1  1/4126 (0.02%)  1/4105 (0.02%) 
Retroperitoneal abscess  1  0/4126 (0.00%)  1/4105 (0.02%) 
Rhinitis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Scrotal abscess  1  1/4126 (0.02%)  0/4105 (0.00%) 
Sepsis  1  17/4126 (0.41%)  3/4105 (0.07%) 
Septic shock  1  2/4126 (0.05%)  1/4105 (0.02%) 
Sinusitis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Soft tissue infection  1  1/4126 (0.02%)  0/4105 (0.00%) 
Streptococcal infection  1  1/4126 (0.02%)  0/4105 (0.00%) 
Subdiaphragmatic abscess  1  0/4126 (0.00%)  1/4105 (0.02%) 
Testicular abscess  1  2/4126 (0.05%)  0/4105 (0.00%) 
Tonsillitis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Tuberculosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Upper respiratory tract infection  1  0/4126 (0.00%)  1/4105 (0.02%) 
Urinary tract infection  1  6/4126 (0.15%)  4/4105 (0.10%) 
Urinary tract infection bacterial  1  1/4126 (0.02%)  0/4105 (0.00%) 
Urosepsis  1  6/4126 (0.15%)  4/4105 (0.10%) 
Vestibular neuronitis  1  2/4126 (0.05%)  0/4105 (0.00%) 
Viral infection  1  2/4126 (0.05%)  0/4105 (0.00%) 
Viral labyrinthitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Wound infection  1  1/4126 (0.02%)  1/4105 (0.02%) 
Injury, poisoning and procedural complications     
Post procedural haemorrhage  1  8/4126 (0.19%)  7/4105 (0.17%) 
Rib fracture  1  2/4126 (0.05%)  6/4105 (0.15%) 
Road traffic accident  1  5/4126 (0.12%)  3/4105 (0.07%) 
Tibia fracture  1  6/4126 (0.15%)  2/4105 (0.05%) 
Post procedural complication  1  4/4126 (0.10%)  4/4105 (0.10%) 
Femur fracture  1  4/4126 (0.10%)  3/4105 (0.07%) 
Meniscus lesion  1  3/4126 (0.07%)  4/4105 (0.10%) 
Fibula fracture  1  5/4126 (0.12%)  0/4105 (0.00%) 
Urinary retention postoperative  1  1/4126 (0.02%)  4/4105 (0.10%) 
Head injury  1  3/4126 (0.07%)  1/4105 (0.02%) 
Hip fracture  1  1/4126 (0.02%)  3/4105 (0.07%) 
Wound  1  0/4126 (0.00%)  4/4105 (0.10%) 
Lower limb fracture  1  2/4126 (0.05%)  2/4105 (0.05%) 
Post procedural haematuria  1  1/4126 (0.02%)  3/4105 (0.07%) 
Cartilige injury  1  1/4126 (0.02%)  2/4105 (0.05%) 
Femoral neck fracture  1  1/4126 (0.02%)  2/4105 (0.05%) 
Incisional hernia  1  1/4126 (0.02%)  2/4105 (0.05%) 
Injury  1  2/4126 (0.05%)  1/4105 (0.02%) 
Joint dislocation  1  1/4126 (0.02%)  2/4105 (0.05%) 
Multiple injuries  1  1/4126 (0.02%)  2/4105 (0.05%) 
Scapula fracture  1  2/4126 (0.05%)  1/4105 (0.02%) 
Tendon rupture  1  2/4126 (0.05%)  1/4105 (0.02%) 
Ulna fracture  1  1/4126 (0.02%)  2/4105 (0.05%) 
Lumbar vertebral fracture  1  3/4126 (0.07%)  0/4105 (0.00%) 
Skeletal injury  1  2/4126 (0.05%)  1/4105 (0.02%) 
Ankle fracture  1  1/4126 (0.02%)  1/4105 (0.02%) 
Concussion  1  1/4126 (0.02%)  1/4105 (0.02%) 
Facial bones fracture  1  1/4126 (0.02%)  1/4105 (0.02%) 
Foot fracture  1  2/4126 (0.05%)  0/4105 (0.00%) 
Humerus fracture  1  1/4126 (0.02%)  1/4105 (0.02%) 
Multiple fractures  1  2/4126 (0.05%)  0/4105 (0.00%) 
Patella fracture  1  2/4126 (0.05%)  0/4105 (0.00%) 
Radius fracture  1  0/4126 (0.00%)  2/4105 (0.05%) 
Splenic rupture  1  1/4126 (0.02%)  1/4105 (0.02%) 
Sternal fracture  1  0/4126 (0.00%)  2/4105 (0.05%) 
Subdural haematoma  1  0/4126 (0.00%)  2/4105 (0.05%) 
Subdural haemorrhage  1  1/4126 (0.02%)  1/4105 (0.02%) 
Brain contusion  1  1/4126 (0.02%)  1/4105 (0.02%) 
Comminuted fracture  1  2/4126 (0.05%)  0/4105 (0.00%) 
Postoperative ileus  1  1/4126 (0.02%)  1/4105 (0.02%) 
Joint injury  1  2/4126 (0.05%)  0/4105 (0.00%) 
Limb traumatic amputation  1  2/4126 (0.05%)  0/4105 (0.00%) 
Procedural hypotension  1  0/4126 (0.00%)  2/4105 (0.05%) 
Post procedural haematoma  1  0/4126 (0.00%)  2/4105 (0.05%) 
Accidental overdose  1  0/4126 (0.00%)  1/4105 (0.02%) 
Animal bite  1  0/4126 (0.00%)  1/4105 (0.02%) 
Back injury  1  0/4126 (0.00%)  1/4105 (0.02%) 
Clavicle fracture  1  1/4126 (0.02%)  0/4105 (0.00%) 
Collapse of lung  1  0/4126 (0.00%)  1/4105 (0.02%) 
Fall  1  0/4126 (0.00%)  1/4105 (0.02%) 
Forearm fracture  1  0/4126 (0.00%)  1/4105 (0.02%) 
Foreign body trauma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Intentional overdose  1  1/4126 (0.02%)  0/4105 (0.00%) 
Jaw fracture  1  0/4126 (0.00%)  1/4105 (0.02%) 
Laceration  1  0/4126 (0.00%)  1/4105 (0.02%) 
Muscle injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Overdose  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pneumothorax traumatic  1  1/4126 (0.02%)  0/4105 (0.00%) 
Procedural site reaction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Skull fractured base  1  1/4126 (0.02%)  0/4105 (0.00%) 
Spinal cord injury  1  0/4126 (0.00%)  1/4105 (0.02%) 
Traumatic haematoma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Urethral injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Anaemia postoperative  1  0/4126 (0.00%)  1/4105 (0.02%) 
Vascular graft occlusion  1  0/4126 (0.00%)  1/4105 (0.02%) 
Excoriation  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cervical vertebral fracture  1  0/4126 (0.00%)  1/4105 (0.02%) 
Thoracic vertebral fracture  1  0/4126 (0.00%)  1/4105 (0.02%) 
Muscle strain  1  1/4126 (0.02%)  0/4105 (0.00%) 
Anastomotic leak  1  0/4126 (0.00%)  1/4105 (0.02%) 
Contusion  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cardiac valve replacement complication  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intervertebral disc injury  1  0/4126 (0.00%)  1/4105 (0.02%) 
Blast injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Coronary artery restenosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Skin laceration  1  1/4126 (0.02%)  0/4105 (0.00%) 
Adrenal haematoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Traumatic brain injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Abdominal injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Crush injury  1  0/4126 (0.00%)  1/4105 (0.02%) 
Eye injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pelvic fracture  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gastrointestinal injury  1  0/4126 (0.00%)  1/4105 (0.02%) 
Limb injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Poisoning  1  0/4126 (0.00%)  1/4105 (0.02%) 
Skull fracture  1  1/4126 (0.02%)  0/4105 (0.00%) 
Chest injury  1  0/4126 (0.00%)  1/4105 (0.02%) 
Renal injury  1  1/4126 (0.02%)  0/4105 (0.00%) 
Traumatic coma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Ligament rupture  1  0/4126 (0.00%)  1/4105 (0.02%) 
Abdominal wound dehiscence  1  1/4126 (0.02%)  0/4105 (0.00%) 
Investigations     
Hepatic enzyme increased  1  0/4126 (0.00%)  2/4105 (0.05%) 
Alanine aminotransferase increased  1  1/4126 (0.02%)  0/4105 (0.00%) 
Aspartate aminotransferase increased  1  1/4126 (0.02%)  0/4105 (0.00%) 
Blood pressure decreased  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cardiac enzymes increased  1  0/4126 (0.00%)  1/4105 (0.02%) 
Full blood count abnormal  1  0/4126 (0.00%)  1/4105 (0.02%) 
Heart rate increased  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hepatic enzyme abnormal  1  1/4126 (0.02%)  0/4105 (0.00%) 
Metabolism and nutrition disorders     
Arthralgia  1  2/4126 (0.05%)  6/4105 (0.15%) 
Dehydration  1  1/4126 (0.02%)  3/4105 (0.07%) 
Type 2 diabetes mellitus  1  3/4126 (0.07%)  1/4105 (0.02%) 
Hypokalaemia  1  1/4126 (0.02%)  2/4105 (0.05%) 
Insulin-requiring Type 2 diabetes mellitus  1  0/4126 (0.00%)  2/4105 (0.05%) 
Diabetes mellitus  1  1/4126 (0.02%)  0/4105 (0.00%) 
Diabetes mellitus inadequate control  1  0/4126 (0.00%)  1/4105 (0.02%) 
Electrolyte imbalance  1  0/4126 (0.00%)  1/4105 (0.02%) 
Gout  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hypercalcaemia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hypercholesterolaemia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hypoglycaemia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Diabetic foot  1  0/4126 (0.00%)  1/4105 (0.02%) 
Malnutrition  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hyperlipidaemia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  26/4126 (0.63%)  39/4105 (0.95%) 
Intervertebral disc protusion  1  6/4126 (0.15%)  6/4105 (0.15%) 
Back pain  1  4/4126 (0.10%)  6/4105 (0.15%) 
Arthritis  1  3/4126 (0.07%)  4/4105 (0.10%) 
Rotator cuff syndrome  1  4/4126 (0.10%)  3/4105 (0.07%) 
Lumbar spinal stenosis  1  3/4126 (0.07%)  2/4105 (0.05%) 
Musculoskeletal pain  1  1/4126 (0.02%)  4/4105 (0.10%) 
Spinal column stenosis  1  2/4126 (0.05%)  3/4105 (0.07%) 
Foot deformity  1  3/4126 (0.07%)  1/4105 (0.02%) 
Bone pain  1  3/4126 (0.07%)  0/4105 (0.00%) 
Dupuytren's contracture  1  3/4126 (0.07%)  0/4105 (0.00%) 
Intervertebral disc disorder  1  0/4126 (0.00%)  3/4105 (0.07%) 
Osteoporosis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Pain in extremity  1  1/4126 (0.02%)  1/4105 (0.02%) 
Spinal osteoarthritis  1  0/4126 (0.00%)  2/4105 (0.05%) 
Musculoskeletal chest pain  1  0/4126 (0.00%)  2/4105 (0.05%) 
Knee deformity  1  0/4126 (0.00%)  2/4105 (0.05%) 
Arthropathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bunion  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bursitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cervical spinal stenosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Fracture nonunion  1  0/4126 (0.00%)  1/4105 (0.02%) 
Groin pain  1  0/4126 (0.00%)  1/4105 (0.02%) 
Muscle haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Muscular weakness  1  0/4126 (0.00%)  1/4105 (0.02%) 
Myalgia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Neck pain  1  1/4126 (0.02%)  0/4105 (0.00%) 
Osteochondrosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Osteonecrosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Polymyalgia rheumatica  1  0/4126 (0.00%)  1/4105 (0.02%) 
Tendonitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Musculoskeletal disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Patellofemoral pain syndrome  1  1/4126 (0.02%)  0/4105 (0.00%) 
Extraskeletal ossification  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intervertebral disc degeneration  1  1/4126 (0.02%)  0/4105 (0.00%) 
Tendon pain  1  1/4126 (0.02%)  0/4105 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acoustic neuroma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Acute myeloid leukaemia  1  0/4126 (0.00%)  3/4105 (0.07%) 
Adenocarcinoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Adenoma benign  1  1/4126 (0.02%)  0/4105 (0.00%) 
B-cell lymphoma  1  1/4126 (0.02%)  1/4105 (0.02%) 
Basal cell carcinoma  1  5/4126 (0.12%)  2/4105 (0.05%) 
Benign colonic neoplasm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Benign gastric neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Benign gastrointestinal neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Benign neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Benign neoplasm of bladder  1  1/4126 (0.02%)  1/4105 (0.02%) 
Benign neoplasm of thyroid gland  1  0/4126 (0.00%)  1/4105 (0.02%) 
Benign renal neoplasm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bladder cancer  1  7/4126 (0.17%)  7/4105 (0.17%) 
Bladder cancer recurrent  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bladder papilloma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Bladder transitional cell carcinoma  1  1/4126 (0.02%)  3/4105 (0.07%) 
Bladder transitional cell carcinoma recurrent  1  0/4126 (0.00%)  2/4105 (0.05%) 
Bone neoplasm malignant  1  2/4126 (0.05%)  0/4105 (0.00%) 
Brain neoplasm benign  1  1/4126 (0.02%)  2/4105 (0.05%) 
Brain neoplasm malignant  1  0/4126 (0.00%)  2/4105 (0.05%) 
Brain stem glioma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Bronchial carcinoma  1  4/4126 (0.10%)  2/4105 (0.05%) 
Cardiac myxoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Chronic lymphocytic leukemia  1  0/4126 (0.00%)  2/4105 (0.05%) 
Chronic myelomonocytic leukemia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Colon cancer  1  12/4126 (0.29%)  11/4105 (0.27%) 
Colon cancer metastatic  1  1/4126 (0.02%)  0/4105 (0.00%) 
Colon cancer recurrent  1  1/4126 (0.02%)  1/4105 (0.02%) 
Colon cancer stage 0  1  0/4126 (0.00%)  1/4105 (0.02%) 
Colorectal cancer  1  1/4126 (0.02%)  1/4105 (0.02%) 
Dysplastic naevus syndrome  1  0/4126 (0.00%)  1/4105 (0.02%) 
Fibromatosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gastric adenoma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gastric carcinoma  1  3/4126 (0.07%)  3/4105 (0.07%) 
Gastrointestinal cancer  1  5/4126 (0.12%)  3/4105 (0.07%) 
Gastrointestinal neoplasm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Head and neck cancer  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hepatic neoplasm malignant  1  3/4126 (0.07%)  0/4105 (0.00%) 
Intestinal adenocarcinoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Laryngeal cancer  1  1/4126 (0.02%)  1/4105 (0.02%) 
Laryngeal neoplasm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Laryngeal papilloma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Leiomyosarcoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Leukaemia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Lung adenocarcinoma  1  2/4126 (0.05%)  0/4105 (0.00%) 
Lung cancer metastatic  1  1/4126 (0.02%)  1/4105 (0.02%) 
Lung neoplasm  1  13/4126 (0.32%)  12/4105 (0.29%) 
Lung squamous cell carcinoma stage unspecified  1  1/4126 (0.02%)  1/4105 (0.02%) 
Lymphocytic lymphoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Lymphoma  1  3/4126 (0.07%)  0/4105 (0.00%) 
Lymphoproliferative disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Malignant melanoma  1  1/4126 (0.02%)  6/4105 (0.15%) 
Melanocytic naevus  1  0/4126 (0.00%)  1/4105 (0.02%) 
Meningeal neoplasm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Metastases to bone  1  1/4126 (0.02%)  1/4105 (0.02%) 
Metastases to central nervous system  1  0/4126 (0.00%)  3/4105 (0.07%) 
Metastases to liver  1  5/4126 (0.12%)  1/4105 (0.02%) 
Metastases to lung  1  1/4126 (0.02%)  1/4105 (0.02%) 
Metastases to lymph nodes  1  1/4126 (0.02%)  0/4105 (0.00%) 
Metastases to peritoneum  1  1/4126 (0.02%)  0/4105 (0.00%) 
Metastases to pleura  1  0/4126 (0.00%)  1/4105 (0.02%) 
Metastatic malignant melanoma  1  1/4126 (0.02%)  2/4105 (0.05%) 
Metastatic neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Metastatic salivary gland cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Multiple myeloma  1  2/4126 (0.05%)  1/4105 (0.02%) 
Nasopharyngeal cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Neoplasm malignant  1  1/4126 (0.02%)  0/4105 (0.00%) 
Neuroendocrine carcinoma  1  2/4126 (0.05%)  0/4105 (0.00%) 
Neuroendocrine tumor  1  1/4126 (0.02%)  0/4105 (0.00%) 
Non-Hodgkin's lymphoma  1  1/4126 (0.02%)  3/4105 (0.07%) 
Non-Hodgkin’s lymphoma recurrent  1  0/4126 (0.00%)  1/4105 (0.02%) 
Non-small cell lung cancer  1  1/4126 (0.02%)  0/4105 (0.00%) 
Non-small cell lung cancer metastatic  1  0/4126 (0.00%)  1/4105 (0.02%) 
Oesophageal carcinoma  1  3/4126 (0.07%)  1/4105 (0.02%) 
Oesophageal neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pancreatic carcinoma  1  4/4126 (0.10%)  1/4105 (0.02%) 
Pancreatic carcinoma metastatic  1  1/4126 (0.02%)  1/4105 (0.02%) 
Paraganglion neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Penis carcinoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pharyngeal cancer stage unspecified  1  0/4126 (0.00%)  1/4105 (0.02%) 
Prostate cancer  1  3/4126 (0.07%)  4/4105 (0.10%) 
Rectal cancer  1  3/4126 (0.07%)  5/4105 (0.12%) 
Rectal neoplasm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Renal cancer  1  2/4126 (0.05%)  5/4105 (0.12%) 
Renal cancer metastatic  1  0/4126 (0.00%)  1/4105 (0.02%) 
Renal cell carcinoma  1  5/4126 (0.12%)  3/4105 (0.07%) 
Renal neoplasm  1  0/4126 (0.00%)  1/4105 (0.02%) 
Renal oncocytoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Salivary gland cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Skin cancer  1  1/4126 (0.02%)  2/4105 (0.05%) 
Small intestine carcinoma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Squamous cell carcinoma  1  2/4126 (0.05%)  0/4105 (0.00%) 
Testis cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Throat cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Thyroid adenoma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Thyroid cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Tongue neoplasm malignant stage unspecified  1  1/4126 (0.02%)  0/4105 (0.00%) 
Tonsil cancer  1  1/4126 (0.02%)  0/4105 (0.00%) 
Transitional cell carcinoma  1  1/4126 (0.02%)  0/4105 (0.00%) 
Ureteric cancer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Nervous system disorders     
Cerebrovascular accident  1  19/4126 (0.46%)  22/4105 (0.54%) 
Transient ischaemic attack  1  13/4126 (0.32%)  8/4105 (0.19%) 
Syncope  1  6/4126 (0.15%)  9/4105 (0.22%) 
Cerebral infarction  1  2/4126 (0.05%)  5/4105 (0.12%) 
Dizziness  1  6/4126 (0.15%)  1/4105 (0.02%) 
Carotid artery stenosis  1  2/4126 (0.05%)  4/4105 (0.10%) 
Epilepsy  1  3/4126 (0.07%)  3/4105 (0.07%) 
Cerebrovascular disorder  1  2/4126 (0.05%)  1/4105 (0.02%) 
Haemorrhagic stroke  1  0/4126 (0.00%)  3/4105 (0.07%) 
Headache  1  2/4126 (0.05%)  1/4105 (0.02%) 
Loss of consciousness  1  3/4126 (0.07%)  0/4105 (0.00%) 
Presyncope  1  1/4126 (0.02%)  2/4105 (0.05%) 
Cartoid artery occlusion  1  1/4126 (0.02%)  2/4105 (0.05%) 
Lacunar infarction  1  2/4126 (0.05%)  1/4105 (0.02%) 
Amnesia  1  1/4126 (0.02%)  1/4105 (0.02%) 
Carpal tunnel syndrome  1  1/4126 (0.02%)  1/4105 (0.02%) 
Cerebral ischaemia  1  1/4126 (0.02%)  1/4105 (0.02%) 
Cerebral thrombosis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Convulsion  1  1/4126 (0.02%)  1/4105 (0.02%) 
Dementia  1  1/4126 (0.02%)  1/4105 (0.02%) 
Hypoaesthesia  1  1/4126 (0.02%)  1/4105 (0.02%) 
Myasthenia gravis  1  2/4126 (0.05%)  0/4105 (0.00%) 
Myelopathy  1  0/4126 (0.00%)  2/4105 (0.05%) 
Subarachnoid haemorrhage  1  2/4126 (0.05%)  0/4105 (0.00%) 
Ischaemic stroke  1  1/4126 (0.02%)  1/4105 (0.02%) 
Amyotrophic lateral sclerosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Ataxia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Brain stem infarction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cerebral artery embolism  1  0/4126 (0.00%)  1/4105 (0.02%) 
Cerebral haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Dementia Alzheimer's type  1  0/4126 (0.00%)  1/4105 (0.02%) 
Haemorrhagic cerebral infarction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hemiparesis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hypertonia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intracranial aneurysm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Intracranial pressure increased  1  0/4126 (0.00%)  1/4105 (0.02%) 
Migraine  1  0/4126 (0.00%)  1/4105 (0.02%) 
Migraine with aura  1  0/4126 (0.00%)  1/4105 (0.02%) 
Motor neurone disease  1  0/4126 (0.00%)  1/4105 (0.02%) 
Nerve compression  1  1/4126 (0.02%)  0/4105 (0.00%) 
Nervous system disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Neuropathy peripheral  1  0/4126 (0.00%)  1/4105 (0.02%) 
Paraplegia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Paresis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Peripheral sensory neuropathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Sciatica  1  0/4126 (0.00%)  1/4105 (0.02%) 
Spinal claudication  1  0/4126 (0.00%)  1/4105 (0.02%) 
Syringomyelia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Temporal lobe epilepsy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Arachnoid cyst  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cartoid sinus syndrome  1  0/4126 (0.00%)  1/4105 (0.02%) 
Facial paresis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Radicular syndrome  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cubital tunnel syndrome  1  0/4126 (0.00%)  1/4105 (0.02%) 
Global amnesia  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cluster headache  1  0/4126 (0.00%)  1/4105 (0.02%) 
Parkinson's Disease  1  1/4126 (0.02%)  0/4105 (0.00%) 
Cartoid artery disease  1  1/4126 (0.02%)  0/4105 (0.00%) 
Metabolic encephalopathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Vascular encephalopathy  1  0/4126 (0.00%)  1/4105 (0.02%) 
Thalamic infarction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hemicephalalgia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Psychiatric disorders     
Depression  1  3/4126 (0.07%)  3/4105 (0.07%) 
Anxiety  1  2/4126 (0.05%)  2/4105 (0.05%) 
Confusional state  1  2/4126 (0.05%)  0/4105 (0.00%) 
Suicide attempt  1  1/4126 (0.02%)  1/4105 (0.02%) 
Mental change status  1  2/4126 (0.05%)  0/4105 (0.00%) 
Mental disorder  1  0/4126 (0.00%)  2/4105 (0.05%) 
Alcohol abuse  1  0/4126 (0.00%)  1/4105 (0.02%) 
Alcoholic psychosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Alcoholism  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bipolar I disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Delirium  1  0/4126 (0.00%)  1/4105 (0.02%) 
Generalised anxiety disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Panic disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Impaired self-care  1  1/4126 (0.02%)  0/4105 (0.00%) 
Major depression  1  1/4126 (0.02%)  0/4105 (0.00%) 
Burnout syndrome  1  1/4126 (0.02%)  0/4105 (0.00%) 
Renal and urinary disorders     
Urinary retention  1  17/4126 (0.41%)  3/4105 (0.07%) 
Calculus ureteric  1  5/4126 (0.12%)  11/4105 (0.27%) 
Nephrolithiasis  1  7/4126 (0.17%)  8/4105 (0.19%) 
Haematuria  1  9/4126 (0.22%)  3/4105 (0.07%) 
Renal failure  1  5/4126 (0.12%)  3/4105 (0.07%) 
Renal colic  1  3/4126 (0.07%)  4/4105 (0.10%) 
Calculus bladder  1  3/4126 (0.07%)  3/4105 (0.07%) 
Renal failure acute  1  3/4126 (0.07%)  1/4105 (0.02%) 
Urinary bladder haemorrhage  1  3/4126 (0.07%)  1/4105 (0.02%) 
Urethral stenosis  1  3/4126 (0.07%)  0/4105 (0.00%) 
Bladder neck obstruction  1  0/4126 (0.00%)  1/4105 (0.02%) 
Calculus urinary  1  1/4126 (0.02%)  0/4105 (0.00%) 
Dysuria  1  1/4126 (0.02%)  0/4105 (0.00%) 
Extravasation of urine  1  1/4126 (0.02%)  0/4105 (0.00%) 
Hydronephrosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Obstructive uropathy  1  1/4126 (0.02%)  0/4105 (0.00%) 
Renal cyst  1  1/4126 (0.02%)  0/4105 (0.00%) 
Renal disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Renal failure chronic  1  1/4126 (0.02%)  0/4105 (0.00%) 
Urethral disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Urethral obstruction  1  1/4126 (0.02%)  0/4105 (0.00%) 
Urinary tract disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Urinoma  1  0/4126 (0.00%)  1/4105 (0.02%) 
Hyperuricosuria  1  1/4126 (0.02%)  0/4105 (0.00%) 
Bladder tamponade  1  0/4126 (0.00%)  1/4105 (0.02%) 
Reproductive system and breast disorders     
Prostatitis  1  18/4126 (0.44%)  1/4105 (0.02%) 
Benign prostatic hyperplasia  1  10/4126 (0.24%)  5/4105 (0.12%) 
Epididymitis  1  4/4126 (0.10%)  6/4105 (0.15%) 
Prostatism  1  2/4126 (0.05%)  0/4105 (0.00%) 
Prostatomegaly  1  2/4126 (0.05%)  0/4105 (0.00%) 
Epididymal cyst  1  1/4126 (0.02%)  0/4105 (0.00%) 
Gynaecomastia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Peyronie's Disease  1  0/4126 (0.00%)  1/4105 (0.02%) 
Prostatic haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Retrograde ejaculation  1  0/4126 (0.00%)  1/4105 (0.02%) 
Testicular cyst  1  1/4126 (0.02%)  0/4105 (0.00%) 
Genital discomfort  1  0/4126 (0.00%)  1/4105 (0.02%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  11/4126 (0.27%)  6/4105 (0.15%) 
Dyspnoea  1  7/4126 (0.17%)  6/4105 (0.15%) 
Chronic obstructive pulmonary disease  1  5/4126 (0.12%)  4/4105 (0.10%) 
Asthma  1  3/4126 (0.07%)  2/4105 (0.05%) 
Epistaxis  1  2/4126 (0.05%)  2/4105 (0.05%) 
Pleural effusion  1  1/4126 (0.02%)  3/4105 (0.07%) 
Bronchitis chronic  1  2/4126 (0.05%)  1/4105 (0.02%) 
Emphysema  1  1/4126 (0.02%)  2/4105 (0.05%) 
Haemothorax  1  1/4126 (0.02%)  2/4105 (0.05%) 
Nasal polyps  1  3/4126 (0.07%)  0/4105 (0.00%) 
Pulmonary hypertension  1  3/4126 (0.07%)  0/4105 (0.00%) 
Haemoptysis  1  1/4126 (0.02%)  1/4105 (0.02%) 
Hypoxia  1  2/4126 (0.05%)  0/4105 (0.00%) 
Pleurisy  1  2/4126 (0.05%)  0/4105 (0.00%) 
Pneumothorax  1  0/4126 (0.00%)  2/4105 (0.05%) 
Vocal cord polyp  1  2/4126 (0.05%)  0/4105 (0.00%) 
Acute pulmonary oedema  1  0/4126 (0.00%)  1/4105 (0.02%) 
Lung disorder  1  1/4126 (0.02%)  0/4105 (0.00%) 
Lung infiltration  1  1/4126 (0.02%)  0/4105 (0.00%) 
Nasal congestion  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pleuritic pain  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pneumonitis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pulmonary congestion  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pulmonary fibrosis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Pulmonary oedema  1  1/4126 (0.02%)  0/4105 (0.00%) 
Respiratory acidosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Respiratory failure  1  0/4126 (0.00%)  1/4105 (0.02%) 
Sleep apnoea syndrome  1  0/4126 (0.00%)  1/4105 (0.02%) 
Adenoidal disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Bronchial hyperreactivity  1  1/4126 (0.02%)  0/4105 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Dermatitis allergic  1  0/4126 (0.00%)  1/4105 (0.02%) 
Dermatitis bullous  1  1/4126 (0.02%)  0/4105 (0.00%) 
Dry skin  1  1/4126 (0.02%)  0/4105 (0.00%) 
Erythema  1  1/4126 (0.02%)  0/4105 (0.00%) 
Skin necrosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Skin ulcer  1  0/4126 (0.00%)  1/4105 (0.02%) 
Vasculitic rash  1  0/4126 (0.00%)  1/4105 (0.02%) 
Pruritus generalised  1  0/4126 (0.00%)  1/4105 (0.02%) 
Social circumstances     
Joint prosthesis user  1  0/4126 (0.00%)  1/4105 (0.02%) 
Vascular disorders     
Hypertension  1  10/4126 (0.24%)  8/4105 (0.19%) 
Deep vein thrombosis  1  8/4126 (0.19%)  6/4105 (0.15%) 
Aortic aneurysm  1  5/4126 (0.12%)  5/4105 (0.12%) 
Hypertensive crisis  1  3/4126 (0.07%)  4/4105 (0.10%) 
Arteriosclerosis  1  1/4126 (0.02%)  3/4105 (0.07%) 
Hypotension  1  3/4126 (0.07%)  1/4105 (0.02%) 
Thrombophlebitis  1  1/4126 (0.02%)  3/4105 (0.07%) 
Aortic stenosis  1  2/4126 (0.05%)  1/4105 (0.02%) 
Haematoma  1  1/4126 (0.02%)  2/4105 (0.05%) 
Intermittent claudication  1  1/4126 (0.02%)  2/4105 (0.05%) 
Orthostatic hypotension  1  0/4126 (0.00%)  3/4105 (0.07%) 
Thrombosis  1  0/4126 (0.00%)  3/4105 (0.07%) 
Varicose vein  1  3/4126 (0.07%)  0/4105 (0.00%) 
Aortic aneurysm rupture  1  1/4126 (0.02%)  1/4105 (0.02%) 
Venous thrombosis  1  2/4126 (0.05%)  0/4105 (0.00%) 
Aneurysm ruptured  1  2/4126 (0.05%)  0/4105 (0.00%) 
Peripheral artery aneurysm  1  1/4126 (0.02%)  1/4105 (0.02%) 
Aortic rupture  1  1/4126 (0.02%)  1/4105 (0.02%) 
Peripheral arterial occlusive disease  1  2/4126 (0.05%)  0/4105 (0.00%) 
Aneurysm  1  1/4126 (0.02%)  0/4105 (0.00%) 
Aortic dissection  1  1/4126 (0.02%)  0/4105 (0.00%) 
Arterial thrombosis limb  1  0/4126 (0.00%)  1/4105 (0.02%) 
Circulatory collapse  1  1/4126 (0.02%)  0/4105 (0.00%) 
Femoral arterial stenosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Iliac artery thrombosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Labile blood pressure  1  1/4126 (0.02%)  0/4105 (0.00%) 
Necrosis ischaemic  1  0/4126 (0.00%)  1/4105 (0.02%) 
Peripheral ischaemia  1  0/4126 (0.00%)  1/4105 (0.02%) 
Peripheral vascular disorder  1  0/4126 (0.00%)  1/4105 (0.02%) 
Phlebitis  1  1/4126 (0.02%)  0/4105 (0.00%) 
Lymphocele  1  1/4126 (0.02%)  0/4105 (0.00%) 
Wound haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Iliac artery stenosis  1  0/4126 (0.00%)  1/4105 (0.02%) 
Vascular insufficiency  1  1/4126 (0.02%)  0/4105 (0.00%) 
Haemorrhage  1  1/4126 (0.02%)  0/4105 (0.00%) 
Venous occlusion  1  0/4126 (0.00%)  1/4105 (0.02%) 
Peripheral embolism  1  1/4126 (0.02%)  0/4105 (0.00%) 
Venous thrombosis limb  1  0/4126 (0.00%)  1/4105 (0.02%) 
Aortic elongation  1  1/4126 (0.02%)  0/4105 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Dutasteride 0.5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   1151/4126 (27.90%)   1296/4105 (31.57%) 
Cardiac disorders     
Hypertension  1  321/4126 (7.78%)  349/4105 (8.50%) 
Infections and infestations     
Nasopharyngitis  1  288/4126 (6.98%)  313/4105 (7.62%) 
Influenza  1  212/4126 (5.14%)  204/4105 (4.97%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  245/4126 (5.94%)  261/4105 (6.36%) 
Reproductive system and breast disorders     
Erectile dysfunction  1  363/4126 (8.80%)  494/4105 (12.03%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications:
Muller RL, Gerber L, Moreira DM, Andriole G, Castro R, Freedland SJ. Baseline Serum Testosterone and DHT Levels and the Risk of Prostate Cancer Detection in the Placebo Arm of the REDUCE Trial. [Eur Urol [E-pub 18 May]]. 2012;
Stephen J. Freedland, Leah Gerber, Lionel Banez, Daniel Moreira, Gerald L. Andriole, and Roger S. Rittmaster on behalf of the REDUCE Study Group. Statin Use and the Risk of Prostate Cancer and High-grade Prostate Cancer: Results from the REDUCE study. [AUA 2011 Annual Meeting]. 2011;185(4 Suppl):e135.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00056407     History of Changes
Other Study ID Numbers: ARI40006
First Submitted: March 11, 2003
First Posted: March 13, 2003
Results First Submitted: February 1, 2010
Results First Posted: March 5, 2010
Last Update Posted: September 23, 2016