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Comparative Efficacy & Safety Study of D961H Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With Low-dose Aspirin

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ClinicalTrials.gov Identifier: NCT01069939
Recruitment Status : Completed
First Posted : February 17, 2010
Results First Posted : November 22, 2012
Last Update Posted : November 22, 2012
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Prevention
Interventions Drug: Esomeprazole
Drug: Placebo
Enrollment 427
Recruitment Details First participant enrolled on 4 February 2010. On 20 May 2011, the efficacy analysis was completed based on positive results of an interim analysis so that the efficacy data in this report are at the interim analysis. To evaluate the safety, the study was continued. The last participant completed the study on 9 November 2011.
Pre-assignment Details Out of 914 enrolled participants, 430 participants were assigned , but 484 participants were not assigned. The major reasons of no assignment were 'Did not meet eligibility criteria' (462 participants) and 'Voluntary discontinuation by participant' (21 participants). After 366 participants were randomised, the interim analysis was done.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description Esomeprazole 20mg once daily oral Placebo once daily oral
Period Title: Randomised and Included in the Analyses
Started 213 214
Completed 164 137
Not Completed 49 77
Reason Not Completed
Adverse Event             17             22
Withdrawal by Subject             15             12
Lost to Follow-up             1             1
Protocol Violation             0             1
Lack of Efficacy             0             1
Study-specific withdrawal criteria             7             33
Eligibility criteria not fulfilled             4             3
Use of prohibited concomitant drug             4             2
Physician Decision             0             2
Removal             1             0
Period Title: At Data Cut Off Date (26 Feb 2011)
Started 213 214
Completed 182 182
Not Completed 31 32
Arm/Group Title Esomeprazole 20mg Placebo Total
Hide Arm/Group Description Esomeprazole 20mg once daily oral Placebo once daily oral Total of all reporting groups
Overall Number of Baseline Participants 213 214 427
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 213 participants 214 participants 427 participants
<=64years 85 71 156
Between 65 and 74 years 82 89 171
>=75 years 46 54 100
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 213 participants 214 participants 427 participants
Female
43
  20.2%
46
  21.5%
89
  20.8%
Male
170
  79.8%
168
  78.5%
338
  79.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 213 participants 214 participants 427 participants
Taiwan 22 21 43
Japan 160 160 320
Korea, Republic of 31 33 64
Helicobacter pylori status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 213 participants 214 participants 427 participants
Positive 93 93 186
Negative 117 116 233
[1]
Measure Description: 8 participants had a missing for this measurement (3 participants in Esomeprazole 20 mg group and 5 participants in Placebo group). Negative means a patient had no Helicobacter pylori infection and Positive means a patient had Helicobacter pylori infection.
1.Primary Outcome
Title Time From Randomization to Occurrence of Gastric and/or Duodenal Ulcers up to Data Cut-off Date for Interim Analysis.
Hide Description Assessments for occurrence of gastric and/or duodenal ulcers were performed every 12 weeks after randomisation. The numbers of participants with recurrence of gastric and/or duodeal ulcers were analysed every 12 weeks up to 48 weeks.
Time Frame From randomisation to up to 48 weeks (Maximum follow-up period at the interim analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants not taking investigational drug were not included. In total 364 participants were included in the efficacy evaluation at the interim analysis. 24 of the 364 total participants had an occurrence of gastric and/or duodenal ulcers by the 48-week assessment.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 182 182
Measure Type: Number
Unit of Measure: Participants
0 - 12 weeks 1 16
13 - 24 weeks 1 4
25 - 36 weeks 0 2
37 - 48 weeks 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Esomeprazole 20mg, Placebo
Comments The above two groups were compared.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments An interim analysis was done so that the significance level was adjusted using the Pocock-like alpha-spending function with Lan-DeMets approach. The adjusted significance level was the two-sided 3.35%.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.09
Confidence Interval (2-Sided) 96.65%
0.02 to 0.41
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Degree of Gastric Mucosal Lesion by Modified Lanza Scale From Baseline to Last Measurement up to Week 48
Hide Description Modified Lanza scale attributes the degree of gastric mucosal lesion, graded on a 5 point scale (0=No hemorrhage, no erosion, 1=One hemorrhage or one erosions, 2=2-10 hemorrhages or erosions, 3=11-25 hemorrhages or erosions, 4=More than 25 hemorrhages or erosions, or ulcer). Higher scores indicate greater severity of gastric mucosal lesion.
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had LANZA scores at both baseline and post-dose were included into this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 144 145
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.4  (0.6) 1.3  (1.6)
3.Secondary Outcome
Title Number of Participants With Reflux Esophagitis Evaluated by the LA Classification up to Week 48.
Hide Description Endoscopy was conducted at 12, 24, 36 and 48 weeks after randomisation. At the endoscopy, participants was evaluated whether they have reflux esophagitis or not.
Time Frame 12, 24, 36 and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with endoscopy were included in the analyses at 12, 24, 36 and 48 weeks after randomisation.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 141 138
Measure Type: Number
Unit of Measure: Participants
12 weeks 0 9
24 weeks 1 6
36 weeks 0 3
48 weeks 0 0
4.Secondary Outcome
Title Change in the Severity of Epigastric Pain From Baseline to Last Measurement up to Week 48
Hide Description The severity of epigastric pain at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had the measurements of epigastric pain at baseline and post-dose up to 48 weeks were included in this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 168 172
Measure Type: Number
Unit of Measure: Participants
Improved 11 16
Unchanged 153 145
Worsened 4 11
5.Secondary Outcome
Title Change in the Severity of Heartburn From Baseline to Last Measurement up to Week 48.
Hide Description The severity of heartburn at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had the measurements of heartburn at baseline and post-dose up to 48 weeks were included in this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 168 172
Measure Type: Number
Unit of Measure: Participants
Improved 7 6
Unchanged 158 154
Worsened 3 12
6.Secondary Outcome
Title Change in the Severity of Anorexia From Baseline to Last Measurement up to Week 48
Hide Description The severity of anorexia at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had the measurements of anorexia at baseline and post-dose up to 48 weeks were included in this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 168 172
Measure Type: Number
Unit of Measure: Participants
Improved 9 10
Unchanged 156 153
Worsened 3 9
7.Secondary Outcome
Title Change in the Severity of Abdomen Enlarged Feeling From Baseline to Last Measurement up to Week
Hide Description The severity of abdomen enlarged feeling at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had the measurements of abdomen enlarged feeling at baseline and post-dose up to 48 weeks were included in this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 168 172
Measure Type: Number
Unit of Measure: Participants
Improved 18 24
Unchanged 141 141
Worsened 9 7
8.Secondary Outcome
Title Change in the Severity of Nausea and/or Vomiting From Baseline to Last Measurement up to Week 48
Hide Description The severity of Nausea and/or Vomiting at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had the measurements of Nausea and/or Vomiting at baseline and post-dose up to 48 weeks were included in this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 168 172
Measure Type: Number
Unit of Measure: Participants
Improved 8 5
Unchanged 160 154
Worsened 0 13
9.Secondary Outcome
Title Change in the Severity of Discomfort in the Stomach From Baseline to Last Measurement up to Week 48
Hide Description The severity of Discomfort in the stomach at baseline and the last measurement up to 48 weeks was obtained (None, Mild, Moderate, Severe). If the value at the last was better in a participant, the participant was categorized into "Improved". If the value was same, categorised into "Unchanged". If the value was worsened, categorise into "Worsened".
Time Frame Up to 48 weeks (Baseline to last measurement)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 168 172
Measure Type: Number
Unit of Measure: Participants
Improved 13 15
Unchanged 150 148
Worsened 5 9
10.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Participants who had at least adverse events (AE) which occurred after receiving study drug were counted.
Time Frame Up to 70 weeks at the longest
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug were included in this analysis.
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description:
Esomeprazole 20mg once daily oral
Placebo once daily oral
Overall Number of Participants Analyzed 214 213
Measure Type: Number
Unit of Measure: Participants
Adverse event 155 139
Adverse event (Frequency>=5%) 70 53
Death 0 0
Serious adverse event other than death 17 15
Adverse event leading to discontinuation of study 17 22
Drug-related adverse event 31 29
Severe adverse event 7 10
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Esomeprazole 20mg Placebo
Hide Arm/Group Description Esomeprazole 20mg once daily oral Placebo once daily oral
All-Cause Mortality
Esomeprazole 20mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Esomeprazole 20mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   17/214 (7.94%)   15/213 (7.04%) 
Cardiac disorders     
Ventricular Tachycardia   0/214 (0.00%)  1/213 (0.47%) 
Acute Myocardial Infarction   0/214 (0.00%)  2/213 (0.94%) 
Coronary Artery Stenosis   1/214 (0.47%)  0/213 (0.00%) 
Arteriosclerosis Coronary Artery   1/214 (0.47%)  0/213 (0.00%) 
Angina Pectoris   1/214 (0.47%)  1/213 (0.47%) 
Gastrointestinal disorders     
Gastritis Erosive   0/214 (0.00%)  1/213 (0.47%) 
Diverticulum Intestinal Haemorrhagic   0/214 (0.00%)  1/213 (0.47%) 
Haemorrhoids   1/214 (0.47%)  0/213 (0.00%) 
Hepatobiliary disorders     
Cholangitis Acute   1/214 (0.47%)  0/213 (0.00%) 
Infections and infestations     
Infective Exacerbation Of Chronic Obstructive Airways Disease   0/214 (0.00%)  1/213 (0.47%) 
Pneumonia   0/214 (0.00%)  1/213 (0.47%) 
Gastroenteritis   0/214 (0.00%)  1/213 (0.47%) 
Urinary Tract Infection   1/214 (0.47%)  0/213 (0.00%) 
Injury, poisoning and procedural complications     
Hip Fracture   0/214 (0.00%)  1/213 (0.47%) 
In-Stent Coronary Artery Restenosis   1/214 (0.47%)  0/213 (0.00%) 
Investigations     
Prostatic Specific Antigen Increased   1/214 (0.47%)  0/213 (0.00%) 
Metabolism and nutrition disorders     
Dehydration   0/214 (0.00%)  1/213 (0.47%) 
Musculoskeletal and connective tissue disorders     
Intervertebral Disc Protrusion   1/214 (0.47%)  0/213 (0.00%) 
Lumbar Spinal Stenosis   1/214 (0.47%)  0/213 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cardiac Myxoma   0/214 (0.00%)  1/213 (0.47%) 
Lung Neoplasm Malignant   0/214 (0.00%)  1/213 (0.47%) 
Malignant Ascites   1/214 (0.47%)  0/213 (0.00%) 
Gastric Cancer   1/214 (0.47%)  1/213 (0.47%) 
Nervous system disorders     
Epilepsy   0/214 (0.00%)  1/213 (0.47%) 
Cerebral Infarction   1/214 (0.47%)  0/213 (0.00%) 
Brain Stem Haemorrhage   2/214 (0.93%)  0/213 (0.00%) 
Renal and urinary disorders     
Renal Infarct   1/214 (0.47%)  0/213 (0.00%) 
Reproductive system and breast disorders     
Epididymitis   1/214 (0.47%)  0/213 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Sleep Apnoea Syndrome   1/214 (0.47%)  0/213 (0.00%) 
Surgical and medical procedures     
Cholecystectomy   1/214 (0.47%)  0/213 (0.00%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Esomeprazole 20mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   70/214 (32.71%)   53/213 (24.88%) 
Gastrointestinal disorders     
Duodenitis   4/214 (1.87%)  11/213 (5.16%) 
Gastric Polyps   11/214 (5.14%)  1/213 (0.47%) 
Constipation   12/214 (5.61%)  11/213 (5.16%) 
Infections and infestations     
Nasopharyngitis   43/214 (20.09%)  30/213 (14.08%) 
Indicates events were collected by systematic assessment
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.
All PIs were prohibited to disclose all information related to this study without AZ approval before this study was completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: aztrial_results_posting@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01069939     History of Changes
Other Study ID Numbers: D961PC00001
First Submitted: February 16, 2010
First Posted: February 17, 2010
Results First Submitted: October 24, 2012
Results First Posted: November 22, 2012
Last Update Posted: November 22, 2012