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Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in High cardiovascUlar Risk Subjects (EBBINGHAUS)

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ClinicalTrials.gov Identifier: NCT02207634
Recruitment Status : Completed
First Posted : August 4, 2014
Results First Posted : January 16, 2018
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Other
Condition Dyslipidemia
Interventions Biological: Evolocumab
Drug: Placebo
Drug: Background Statin Therapy
Enrollment 1974
Recruitment Details

Participants enrolled in Study 20110118 (FOURIER; NCT01764633) at select sites in select countries (based on study start-up timelines) were invited to participate in this cognitive function study.

Participants were enrolled at 340 centers in 29 countries in Europe, North America, and Asia Pacific from September 2014 to July 2015.

Pre-assignment Details There was no separate randomization in this study; each participant received their assigned treatment per Protocol 20110118. Data were analyzed according to Study 20110118 randomized treatment arm.
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study. Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
Period Title: Overall Study
Started 990 984
Received Treatment 990 983
Completed 968 953
Not Completed 22 31
Reason Not Completed
Withdrawal by Subject             21             31
Lost to Follow-up             1             0
Arm/Group Title Placebo Evolocumab Total
Hide Arm/Group Description Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study. Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study. Total of all reporting groups
Overall Number of Baseline Participants 990 984 1974
Hide Baseline Analysis Population Description
Demographic data are provided for all enrolled participants. Baseline Cambridge Neuropsychological Test Automated Battery (CANTAB®) data are provided for all dosed participants enrolled in the study with a baseline cognitive function assessment prior to or on the first dose date of study drug and ≥ 1 post-baseline cognitive measure.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 990 participants 984 participants 1974 participants
62.7  (8.7) 62.9  (8.7) 62.8  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 990 participants 984 participants 1974 participants
Female
274
  27.7%
269
  27.3%
543
  27.5%
Male
716
  72.3%
715
  72.7%
1431
  72.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 990 participants 984 participants 1974 participants
Hispanic or Latino
14
   1.4%
9
   0.9%
23
   1.2%
Not Hispanic or Latino
976
  98.6%
975
  99.1%
1951
  98.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 990 participants 984 participants 1974 participants
American Indian or Alaska Native
2
   0.2%
1
   0.1%
3
   0.2%
Asian
28
   2.8%
31
   3.2%
59
   3.0%
Black or African American
32
   3.2%
28
   2.8%
60
   3.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
3
   0.3%
3
   0.2%
White
910
  91.9%
908
  92.3%
1818
  92.1%
Multiple
1
   0.1%
1
   0.1%
2
   0.1%
Other
17
   1.7%
12
   1.2%
29
   1.5%
Spatial Working Memory (SWM) Strategy Index of Executive Function Raw Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 618 participants 586 participants 1204 participants
17.8  (3.4) 17.8  (3.5) 17.8  (3.4)
[1]
Measure Description: CANTAB is a series of computerized tests to assess cognitive function. The SWM test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found. The SWM strategy index of executive function represents the number of times a patient began a search with a different box. A high score represents an inefficient use of strategy and planning. The raw score ranges from 4 to 28.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Spatial Working Memory (SWM) Strategy Index of Executive Function Z Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Z score
Number Analyzed 618 participants 586 participants 1204 participants
-0.0106  (0.9910) 0.0166  (1.0066) 0.0026  (0.9983)
[1]
Measure Description: The CANTAB SWM test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found. The SWM strategy index of executive function represents the number of times a patient began a search with a different box. The Z score represents the standardized measure of how far an individual deviates from the study cohort average at baseline. A higher Z score reflects better performance.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Spatial Working Memory Between Errors Raw Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 618 participants 586 participants 1204 participants
21.0  (10.6) 20.9  (10.2) 21.0  (10.4)
[1]
Measure Description: The CANTAB Spatial Working Memory (SWM) between-errors score test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found. The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. A lower score indicates better performance. The raw score ranges from 0 to 279.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Spatial Working Memory Between Errors Z Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Z score
Number Analyzed 618 participants 586 participants 1204 participants
-0.0130  (1.0075) 0.0024  (0.9675) -0.0055  (0.9879)
[1]
Measure Description: The CANTAB Spatial Working Memory (SWM) between-errors score test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found The SWM between-errors score is the number of times a patient revisited a box in which a token had already been found. A higher Z score reflects better performance.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Paired Associates Learning (PAL) Total Errors Adjusted Raw Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 618 participants 586 participants 1204 participants
25.2  (18.4) 26.5  (19.3) 25.8  (18.9)
[1]
Measure Description: The CANTAB PAL test assesses memory function (storing/retrieving information by associating an event with a time and place). Boxes on the screen open in turn to reveal a number of patterns. After all the boxes were opened, each pattern was shown in a randomized order and the patient asked to touch the box where they think the pattern was hidden. The PAL total errors adjusted score is the number of errors made plus an adjustment for the estimated number of errors the patient would have made on any stages not reached. A lower score indicates better performance. The raw score ranges from 0 to 70.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Paired Associates Learning Total Errors Adjusted Z Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Z score
Number Analyzed 618 participants 586 participants 1204 participants
0.0442  (0.9834) -0.0272  (1.0294) 0.0095  (1.0063)
[1]
Measure Description: The CANTAB PAL test assesses memory function (storing/retrieving information by associating an event with a time and place). Boxes on the screen open in turn to reveal a number of patterns. After all the boxes have been opened, each pattern was shown in a randomized order and the patient asked to touch the box where they think each pattern was hidden. The PAL total errors adjusted is the number of errors committed plus an adjustment for the estimated number of errors the patient would have made on any stages not reached. Higher Z scores indicate better performance.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Reaction Time Median 5-Choice Reaction Time Raw Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Msec
Number Analyzed 614 participants 585 participants 1199 participants
355.10  (77.60) 356.74  (65.01) 355.90  (71.71)
[1]
Measure Description: The CANTAB Reaction Time (RTI) test assessed psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. A lower score indicates better performance. The raw score ranges from 100 to 5100 msec.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
Reaction Time Median 5-Choice Reaction Time Z Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 614 participants 585 participants 1199 participants
-0.0271  (1.0829) -0.0500  (0.9072) -0.0383  (1.0007)
[1]
Measure Description: The CANTAB Reaction Time (RTI) test assessed psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient moved their finger from the button to the circle in which the spot appeared. The RTI median 5-choice reaction time is the median duration between the onset of the stimulus and the release of the button. A higher Z score reflects better performance.
[2]
Measure Analysis Population Description: All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.
1.Primary Outcome
Title Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score
Hide Description

Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function.

The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.

The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.

Time Frame Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
Hide Outcome Measure Data
Hide Analysis Population Description

All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.

Cognitive function assessments after an on-study stroke event were excluded from the analysis.

Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.
Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
Overall Number of Participants Analyzed 616 586
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Z score
0.1206
(0.0535 to 0.1877)
0.1134
(0.0449 to 0.1820)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments A repeated measures mixed-effect linear model was used to estimate treatment difference (placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening low-density lipoprotein cholesterol [LDL-C] and geographical region), age, education level, baseline SWM strategy index Z score, treatment group, visit, and treatment by visit interaction.
Type of Statistical Test Non-Inferiority
Comments The non-inferiority margin was 0.19, calculated as 20% of the observed common standard deviation, which was estimated from observations in the placebo group by a repeated measured mixed-effect linear model with visit as a covariate. If the upper bound of the 95% CI for the difference between the placebo and evolocumab group in mean change from baseline for Z score averaged across the visits was less than the non-inferiority margin non-inferiority criteria were met.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.0072
Confidence Interval (2-Sided) 95%
-0.0664 to 0.0808
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0375
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score
Hide Description

Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) between-errors test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.

The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. The Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.

Time Frame Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
Hide Outcome Measure Data
Hide Analysis Population Description

All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.

Cognitive function assessments after an on-study stroke event were excluded from the analysis.

Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.
Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
Overall Number of Participants Analyzed 616 586
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Z score
0.1024
(0.0373 to 0.1675)
0.0691
(0.0026 to 0.1355)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments A repeated measures mixed-effect linear model was used to estimate treatment difference (placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening LDL-C and geographical region), age, education level, baseline SWM between-errors Z score, treatment group, visit, and treatment by visit interaction.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.0333
Confidence Interval (2-Sided) 95%
-0.0378 to 0.1045
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0363
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score
Hide Description

The CANTAB PAL test assesses visuospatial episodic memory (storing/retrieving information by associating an event with a time and place). Boxes on the screen opened up one at a time to reveal a number of patterns. Participants were asked to remember the location of each pattern. After all the boxes had been opened, each pattern was then shown in the center of the screen in a randomized order, and the patient should touch the box where they think each pattern was hidden. The PAL total errors adjusted comprised the number of errors committed by a patient plus an adjustment for the estimated number of errors the patient would have made on any stages that were not reached.

Z score represents the standardized measure of how far an individual patient deviates from the study cohort average at baseline. A higher Z score indicated better performance. The mean change from baseline averaged across all the visits is reported.

Time Frame Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
Hide Outcome Measure Data
Hide Analysis Population Description

All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.

Cognitive function assessments after an on-study stroke event were excluded from the analysis.

Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.
Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
Overall Number of Participants Analyzed 615 585
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Z score
0.1098
(0.0511 to 0.1686)
0.0873
(0.0273 to 0.1472)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments A repeated measures mixed-effect linear model was used to estimate treatment difference (placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening LDL-C and geographical region), age, education level, baseline PAL total errors adjusted Z score, treatment group, visit, and treatment by visit interaction.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.0226
Confidence Interval (2-Sided) 95%
-0.0422 to 0.0873
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0330
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score
Hide Description Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Reaction Time (RTI) test assessed the cognitive domain of psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.
Time Frame Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
Hide Outcome Measure Data
Hide Analysis Population Description

All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.

Cognitive function assessments after an on-study stroke event were excluded from the analysis.

Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.
Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
Overall Number of Participants Analyzed 611 584
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Z score
0.0153
(-0.0529 to 0.0834)
-0.0575
(-0.1270 to 0.0121)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments A repeated measures mixed-effect linear model was used to estimate treatment difference ( placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening LDL-C and geographical region), age, education level, baseline RTI median 5-choice reaction time Z score, treatment group, visit, and treatment by visit interaction.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.0727
Confidence Interval (2-Sided) 95%
-0.0022 to 0.1477
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0382
Estimation Comments [Not Specified]
Time Frame From the first dose of study drug to the end of study. The median duration of follow-up was 19.4 months.
Adverse Event Reporting Description

Although there was no separate safety data collection, recording, or reporting planned in this study, an ad-hoc analysis of safety data collected in Study 20110118 was conducted for participants in Study 20130385 and is reported here.

Deaths by any cause were collected as adjudicated efficacy endpoints in Study 20110118 and were reported as a secondary endpoint in Study 20110118.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the 5% frequency threshold.

 
Arm/Group Title Placebo Evolocumab
Hide Arm/Group Description Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study. Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
All-Cause Mortality
Placebo Evolocumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Evolocumab
Affected / at Risk (%) Affected / at Risk (%)
Total   204/990 (20.61%)   212/983 (21.57%) 
Blood and lymphatic system disorders     
Anaemia  1  6/990 (0.61%)  2/983 (0.20%) 
Autoimmune haemolytic anaemia  1  1/990 (0.10%)  0/983 (0.00%) 
Febrile neutropenia  1  0/990 (0.00%)  1/983 (0.10%) 
Haemorrhagic anaemia  1  0/990 (0.00%)  1/983 (0.10%) 
Immune thrombocytopenic purpura  1  0/990 (0.00%)  1/983 (0.10%) 
Iron deficiency anaemia  1  1/990 (0.10%)  1/983 (0.10%) 
Spleen disorder  1  1/990 (0.10%)  0/983 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  0/990 (0.00%)  1/983 (0.10%) 
Acute myocardial infarction  1  1/990 (0.10%)  1/983 (0.10%) 
Angina pectoris  1  16/990 (1.62%)  15/983 (1.53%) 
Angina unstable  1  15/990 (1.52%)  11/983 (1.12%) 
Arrhythmia  1  2/990 (0.20%)  0/983 (0.00%) 
Atrial fibrillation  1  7/990 (0.71%)  13/983 (1.32%) 
Atrial flutter  1  1/990 (0.10%)  1/983 (0.10%) 
Atrioventricular block  1  1/990 (0.10%)  0/983 (0.00%) 
Atrioventricular block complete  1  0/990 (0.00%)  1/983 (0.10%) 
Atrioventricular block second degree  1  1/990 (0.10%)  0/983 (0.00%) 
Bradycardia  1  3/990 (0.30%)  0/983 (0.00%) 
Bundle branch block left  1  0/990 (0.00%)  1/983 (0.10%) 
Cardiac failure  1  4/990 (0.40%)  1/983 (0.10%) 
Cardiac failure acute  1  1/990 (0.10%)  1/983 (0.10%) 
Cardiac failure chronic  1  4/990 (0.40%)  2/983 (0.20%) 
Cardiac failure congestive  1  5/990 (0.51%)  4/983 (0.41%) 
Cardiac tamponade  1  1/990 (0.10%)  0/983 (0.00%) 
Cardiomyopathy  1  0/990 (0.00%)  1/983 (0.10%) 
Congestive cardiomyopathy  1  0/990 (0.00%)  1/983 (0.10%) 
Coronary artery disease  1  3/990 (0.30%)  2/983 (0.20%) 
Dressler's syndrome  1  1/990 (0.10%)  0/983 (0.00%) 
Heart alternation  1  1/990 (0.10%)  0/983 (0.00%) 
Left ventricular dysfunction  1  1/990 (0.10%)  0/983 (0.00%) 
Left ventricular failure  1  0/990 (0.00%)  1/983 (0.10%) 
Mitral valve incompetence  1  0/990 (0.00%)  3/983 (0.31%) 
Mitral valve stenosis  1  0/990 (0.00%)  1/983 (0.10%) 
Myocardial infarction  1  1/990 (0.10%)  0/983 (0.00%) 
Myocarditis  1  0/990 (0.00%)  1/983 (0.10%) 
Pericarditis  1  0/990 (0.00%)  1/983 (0.10%) 
Sinus arrest  1  1/990 (0.10%)  0/983 (0.00%) 
Sinus bradycardia  1  0/990 (0.00%)  1/983 (0.10%) 
Sinus node dysfunction  1  1/990 (0.10%)  1/983 (0.10%) 
Ventricular extrasystoles  1  1/990 (0.10%)  0/983 (0.00%) 
Ventricular fibrillation  1  1/990 (0.10%)  0/983 (0.00%) 
Ventricular tachycardia  1  3/990 (0.30%)  1/983 (0.10%) 
Congenital, familial and genetic disorders     
Intracranial lipoma  1  1/990 (0.10%)  0/983 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  2/990 (0.20%)  1/983 (0.10%) 
Eye disorders     
Cataract  1  2/990 (0.20%)  0/983 (0.00%) 
Iridocyclitis  1  1/990 (0.10%)  0/983 (0.00%) 
Retinal detachment  1  1/990 (0.10%)  0/983 (0.00%) 
Strabismus  1  1/990 (0.10%)  0/983 (0.00%) 
Uveitis  1  1/990 (0.10%)  0/983 (0.00%) 
Visual impairment  1  1/990 (0.10%)  0/983 (0.00%) 
Gastrointestinal disorders     
Abdominal hernia  1  1/990 (0.10%)  2/983 (0.20%) 
Abdominal pain  1  2/990 (0.20%)  2/983 (0.20%) 
Abdominal pain lower  1  1/990 (0.10%)  1/983 (0.10%) 
Abdominal pain upper  1  1/990 (0.10%)  1/983 (0.10%) 
Coeliac artery stenosis  1  1/990 (0.10%)  0/983 (0.00%) 
Colitis  1  1/990 (0.10%)  0/983 (0.00%) 
Colitis ischaemic  1  1/990 (0.10%)  0/983 (0.00%) 
Colitis ulcerative  1  0/990 (0.00%)  1/983 (0.10%) 
Constipation  1  1/990 (0.10%)  1/983 (0.10%) 
Diarrhoea  1  0/990 (0.00%)  1/983 (0.10%) 
Diverticulum  1  0/990 (0.00%)  1/983 (0.10%) 
Duodenal ulcer  1  1/990 (0.10%)  0/983 (0.00%) 
Duodenal ulcer haemorrhage  1  1/990 (0.10%)  0/983 (0.00%) 
Faecaloma  1  0/990 (0.00%)  1/983 (0.10%) 
Gastric disorder  1  1/990 (0.10%)  0/983 (0.00%) 
Gastric ulcer haemorrhage  1  1/990 (0.10%)  1/983 (0.10%) 
Gastric ulcer perforation  1  0/990 (0.00%)  1/983 (0.10%) 
Gastritis  1  2/990 (0.20%)  2/983 (0.20%) 
Gastritis erosive  1  0/990 (0.00%)  1/983 (0.10%) 
Gastritis haemorrhagic  1  1/990 (0.10%)  0/983 (0.00%) 
Gastrointestinal haemorrhage  1  1/990 (0.10%)  0/983 (0.00%) 
Gastrointestinal polyp haemorrhage  1  1/990 (0.10%)  0/983 (0.00%) 
Gastrooesophageal reflux disease  1  2/990 (0.20%)  1/983 (0.10%) 
Haematemesis  1  0/990 (0.00%)  1/983 (0.10%) 
Haematochezia  1  0/990 (0.00%)  1/983 (0.10%) 
Hiatus hernia  1  0/990 (0.00%)  1/983 (0.10%) 
Ileus  1  1/990 (0.10%)  0/983 (0.00%) 
Inguinal hernia  1  1/990 (0.10%)  3/983 (0.31%) 
Large intestine polyp  1  1/990 (0.10%)  0/983 (0.00%) 
Mesenteric artery stenosis  1  0/990 (0.00%)  1/983 (0.10%) 
Oesophageal ulcer  1  0/990 (0.00%)  1/983 (0.10%) 
Pancreatic cyst  1  1/990 (0.10%)  0/983 (0.00%) 
Pancreatitis  1  2/990 (0.20%)  0/983 (0.00%) 
Peptic ulcer  1  1/990 (0.10%)  0/983 (0.00%) 
Reflux gastritis  1  0/990 (0.00%)  1/983 (0.10%) 
Retroperitoneal haemorrhage  1  1/990 (0.10%)  0/983 (0.00%) 
Small intestinal obstruction  1  0/990 (0.00%)  1/983 (0.10%) 
Umbilical hernia  1  0/990 (0.00%)  1/983 (0.10%) 
Vomiting  1  0/990 (0.00%)  1/983 (0.10%) 
General disorders     
Asthenia  1  1/990 (0.10%)  0/983 (0.00%) 
Chest discomfort  1  1/990 (0.10%)  0/983 (0.00%) 
Chest pain  1  4/990 (0.40%)  2/983 (0.20%) 
Non-cardiac chest pain  1  12/990 (1.21%)  6/983 (0.61%) 
Oedema peripheral  1  0/990 (0.00%)  1/983 (0.10%) 
Pyrexia  1  1/990 (0.10%)  0/983 (0.00%) 
Soft tissue inflammation  1  0/990 (0.00%)  1/983 (0.10%) 
Systemic inflammatory response syndrome  1  1/990 (0.10%)  0/983 (0.00%) 
Hepatobiliary disorders     
Cholangitis  1  0/990 (0.00%)  1/983 (0.10%) 
Cholangitis acute  1  1/990 (0.10%)  0/983 (0.00%) 
Cholecystitis  1  0/990 (0.00%)  1/983 (0.10%) 
Cholecystitis acute  1  1/990 (0.10%)  1/983 (0.10%) 
Cholecystitis chronic  1  0/990 (0.00%)  2/983 (0.20%) 
Cholelithiasis  1  1/990 (0.10%)  1/983 (0.10%) 
Cholelithiasis obstructive  1  0/990 (0.00%)  1/983 (0.10%) 
Liver disorder  1  1/990 (0.10%)  0/983 (0.00%) 
Immune system disorders     
Hypersensitivity  1  1/990 (0.10%)  0/983 (0.00%) 
Infections and infestations     
Appendiceal abscess  1  1/990 (0.10%)  0/983 (0.00%) 
Appendicitis  1  1/990 (0.10%)  1/983 (0.10%) 
Bronchitis  1  2/990 (0.20%)  0/983 (0.00%) 
Burkholderia cepacia complex infection  1  1/990 (0.10%)  0/983 (0.00%) 
Cellulitis  1  2/990 (0.20%)  1/983 (0.10%) 
Clostridium difficile infection  1  1/990 (0.10%)  1/983 (0.10%) 
Cystitis  1  0/990 (0.00%)  1/983 (0.10%) 
Device related sepsis  1  1/990 (0.10%)  0/983 (0.00%) 
Diverticulitis  1  0/990 (0.00%)  1/983 (0.10%) 
Escherichia sepsis  1  0/990 (0.00%)  1/983 (0.10%) 
Escherichia urinary tract infection  1  0/990 (0.00%)  1/983 (0.10%) 
Gastroenteritis  1  1/990 (0.10%)  1/983 (0.10%) 
Hepatitis C  1  0/990 (0.00%)  1/983 (0.10%) 
Hepatitis E  1  1/990 (0.10%)  1/983 (0.10%) 
Infectious pleural effusion  1  1/990 (0.10%)  0/983 (0.00%) 
Influenza  1  1/990 (0.10%)  0/983 (0.00%) 
Lower respiratory tract infection  1  2/990 (0.20%)  0/983 (0.00%) 
Lung infection  1  1/990 (0.10%)  0/983 (0.00%) 
Mastoiditis  1  1/990 (0.10%)  0/983 (0.00%) 
Orchitis  1  0/990 (0.00%)  1/983 (0.10%) 
Osteomyelitis  1  2/990 (0.20%)  3/983 (0.31%) 
Peritonitis  1  1/990 (0.10%)  0/983 (0.00%) 
Pneumonia  1  7/990 (0.71%)  10/983 (1.02%) 
Pneumonia bacterial  1  1/990 (0.10%)  2/983 (0.20%) 
Post procedural sepsis  1  0/990 (0.00%)  1/983 (0.10%) 
Pyelonephritis  1  1/990 (0.10%)  0/983 (0.00%) 
Sepsis  1  4/990 (0.40%)  0/983 (0.00%) 
Septic shock  1  1/990 (0.10%)  0/983 (0.00%) 
Streptococcal sepsis  1  1/990 (0.10%)  0/983 (0.00%) 
Upper respiratory tract infection bacterial  1  1/990 (0.10%)  0/983 (0.00%) 
Urinary tract infection  1  0/990 (0.00%)  2/983 (0.20%) 
Urinary tract infection bacterial  1  0/990 (0.00%)  1/983 (0.10%) 
Urosepsis  1  1/990 (0.10%)  0/983 (0.00%) 
Wound infection  1  2/990 (0.20%)  0/983 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  2/990 (0.20%)  0/983 (0.00%) 
Arterial bypass occlusion  1  1/990 (0.10%)  0/983 (0.00%) 
Concussion  1  0/990 (0.00%)  2/983 (0.20%) 
Coronary artery restenosis  1  0/990 (0.00%)  1/983 (0.10%) 
Dislocation of sternum  1  0/990 (0.00%)  1/983 (0.10%) 
Eye injury  1  1/990 (0.10%)  0/983 (0.00%) 
Femur fracture  1  0/990 (0.00%)  2/983 (0.20%) 
Fibula fracture  1  0/990 (0.00%)  1/983 (0.10%) 
Hip fracture  1  1/990 (0.10%)  1/983 (0.10%) 
Incisional hernia  1  0/990 (0.00%)  1/983 (0.10%) 
Intentional overdose  1  1/990 (0.10%)  0/983 (0.00%) 
Meniscus injury  1  0/990 (0.00%)  1/983 (0.10%) 
Peripheral arterial reocclusion  1  0/990 (0.00%)  1/983 (0.10%) 
Peripheral artery restenosis  1  1/990 (0.10%)  1/983 (0.10%) 
Pneumoconiosis  1  0/990 (0.00%)  1/983 (0.10%) 
Pneumonitis chemical  1  0/990 (0.00%)  1/983 (0.10%) 
Post concussion syndrome  1  0/990 (0.00%)  1/983 (0.10%) 
Post procedural constipation  1  1/990 (0.10%)  0/983 (0.00%) 
Post procedural haemorrhage  1  0/990 (0.00%)  1/983 (0.10%) 
Post procedural swelling  1  1/990 (0.10%)  0/983 (0.00%) 
Rib fracture  1  1/990 (0.10%)  0/983 (0.00%) 
Spinal column injury  1  1/990 (0.10%)  0/983 (0.00%) 
Tendon rupture  1  1/990 (0.10%)  0/983 (0.00%) 
Tibia fracture  1  0/990 (0.00%)  1/983 (0.10%) 
Upper limb fracture  1  0/990 (0.00%)  1/983 (0.10%) 
Investigations     
Alanine aminotransferase increased  1  2/990 (0.20%)  0/983 (0.00%) 
Arteriogram coronary  1  1/990 (0.10%)  1/983 (0.10%) 
Aspartate aminotransferase increased  1  1/990 (0.10%)  0/983 (0.00%) 
Blood creatine phosphokinase increased  1  3/990 (0.30%)  0/983 (0.00%) 
Blood potassium increased  1  1/990 (0.10%)  0/983 (0.00%) 
Hepatic enzyme increased  1  0/990 (0.00%)  2/983 (0.20%) 
Liver function test abnormal  1  0/990 (0.00%)  1/983 (0.10%) 
Myocardial necrosis marker increased  1  1/990 (0.10%)  0/983 (0.00%) 
Thyroid function test abnormal  1  0/990 (0.00%)  1/983 (0.10%) 
Metabolism and nutrition disorders     
Cachexia  1  1/990 (0.10%)  0/983 (0.00%) 
Dehydration  1  0/990 (0.00%)  1/983 (0.10%) 
Diabetes mellitus  1  1/990 (0.10%)  2/983 (0.20%) 
Diabetes mellitus inadequate control  1  1/990 (0.10%)  0/983 (0.00%) 
Diabetic ketoacidosis  1  0/990 (0.00%)  1/983 (0.10%) 
Fluid retention  1  1/990 (0.10%)  0/983 (0.00%) 
Gout  1  0/990 (0.00%)  2/983 (0.20%) 
Hyperglycaemia  1  1/990 (0.10%)  0/983 (0.00%) 
Hyperkalaemia  1  1/990 (0.10%)  0/983 (0.00%) 
Hypocalcaemia  1  0/990 (0.00%)  1/983 (0.10%) 
Hypoglycaemia  1  2/990 (0.20%)  1/983 (0.10%) 
Type 2 diabetes mellitus  1  0/990 (0.00%)  1/983 (0.10%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/990 (0.10%)  0/983 (0.00%) 
Arthritis  1  1/990 (0.10%)  0/983 (0.00%) 
Back pain  1  5/990 (0.51%)  0/983 (0.00%) 
Exostosis  1  0/990 (0.00%)  1/983 (0.10%) 
Foot deformity  1  1/990 (0.10%)  2/983 (0.20%) 
Gouty arthritis  1  1/990 (0.10%)  0/983 (0.00%) 
Lumbar spinal stenosis  1  0/990 (0.00%)  1/983 (0.10%) 
Musculoskeletal chest pain  1  2/990 (0.20%)  1/983 (0.10%) 
Myalgia intercostal  1  0/990 (0.00%)  1/983 (0.10%) 
Osteoarthritis  1  3/990 (0.30%)  3/983 (0.31%) 
Pain in extremity  1  0/990 (0.00%)  1/983 (0.10%) 
Pain in jaw  1  0/990 (0.00%)  1/983 (0.10%) 
Polyarthritis  1  1/990 (0.10%)  1/983 (0.10%) 
Polymyalgia rheumatica  1  1/990 (0.10%)  0/983 (0.00%) 
Rhabdomyolysis  1  1/990 (0.10%)  0/983 (0.00%) 
Spinal osteoarthritis  1  1/990 (0.10%)  0/983 (0.00%) 
Synovial cyst  1  1/990 (0.10%)  0/983 (0.00%) 
Tendonitis  1  1/990 (0.10%)  0/983 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma gastric  1  1/990 (0.10%)  0/983 (0.00%) 
Adenocarcinoma of colon  1  0/990 (0.00%)  1/983 (0.10%) 
Benign pancreatic neoplasm  1  0/990 (0.00%)  1/983 (0.10%) 
Bladder cancer  1  0/990 (0.00%)  2/983 (0.20%) 
Bladder transitional cell carcinoma  1  0/990 (0.00%)  1/983 (0.10%) 
Bladder transitional cell carcinoma stage III  1  0/990 (0.00%)  1/983 (0.10%) 
Bronchial carcinoma  1  0/990 (0.00%)  1/983 (0.10%) 
Colon adenoma  1  2/990 (0.20%)  0/983 (0.00%) 
Colon cancer  1  0/990 (0.00%)  1/983 (0.10%) 
Diffuse large B-cell lymphoma  1  1/990 (0.10%)  0/983 (0.00%) 
Gastric cancer  1  1/990 (0.10%)  0/983 (0.00%) 
Invasive ductal breast carcinoma  1  1/990 (0.10%)  0/983 (0.00%) 
Laryngeal cancer stage 0  1  1/990 (0.10%)  0/983 (0.00%) 
Lip and/or oral cavity cancer stage III  1  0/990 (0.00%)  1/983 (0.10%) 
Lung adenocarcinoma  1  1/990 (0.10%)  2/983 (0.20%) 
Lung adenocarcinoma metastatic  1  1/990 (0.10%)  0/983 (0.00%) 
Lung neoplasm  1  1/990 (0.10%)  0/983 (0.00%) 
Lung neoplasm malignant  1  4/990 (0.40%)  1/983 (0.10%) 
Lung squamous cell carcinoma stage III  1  1/990 (0.10%)  0/983 (0.00%) 
Lymphoproliferative disorder  1  1/990 (0.10%)  0/983 (0.00%) 
Meningioma benign  1  1/990 (0.10%)  0/983 (0.00%) 
Metastases to liver  1  1/990 (0.10%)  0/983 (0.00%) 
Metastatic malignant melanoma  1  0/990 (0.00%)  1/983 (0.10%) 
Metastatic squamous cell carcinoma  1  1/990 (0.10%)  0/983 (0.00%) 
Non-small cell lung cancer  1  1/990 (0.10%)  0/983 (0.00%) 
Pancreatic carcinoma  1  1/990 (0.10%)  0/983 (0.00%) 
Papillary thyroid cancer  1  0/990 (0.00%)  1/983 (0.10%) 
Prostate cancer  1  1/990 (0.10%)  1/983 (0.10%) 
Renal cancer metastatic  1  1/990 (0.10%)  0/983 (0.00%) 
Renal cell carcinoma  1  1/990 (0.10%)  1/983 (0.10%) 
Small cell lung cancer  1  0/990 (0.00%)  1/983 (0.10%) 
Squamous cell carcinoma of lung  1  0/990 (0.00%)  1/983 (0.10%) 
Tonsil cancer  1  1/990 (0.10%)  0/983 (0.00%) 
Transitional cell carcinoma  1  0/990 (0.00%)  1/983 (0.10%) 
Uterine leiomyoma  1  0/990 (0.00%)  1/983 (0.10%) 
Nervous system disorders     
Arachnoid cyst  1  1/990 (0.10%)  0/983 (0.00%) 
Balance disorder  1  0/990 (0.00%)  1/983 (0.10%) 
Carotid artery disease  1  1/990 (0.10%)  0/983 (0.00%) 
Carotid artery stenosis  1  5/990 (0.51%)  6/983 (0.61%) 
Carpal tunnel syndrome  1  1/990 (0.10%)  0/983 (0.00%) 
Cerebral ischaemia  1  1/990 (0.10%)  0/983 (0.00%) 
Cerebrovascular accident  1  1/990 (0.10%)  0/983 (0.00%) 
Cervical myelopathy  1  0/990 (0.00%)  1/983 (0.10%) 
Cervicobrachial syndrome  1  1/990 (0.10%)  0/983 (0.00%) 
Dizziness  1  0/990 (0.00%)  1/983 (0.10%) 
Epilepsy  1  0/990 (0.00%)  2/983 (0.20%) 
Facial paralysis  1  1/990 (0.10%)  0/983 (0.00%) 
Generalised tonic-clonic seizure  1  0/990 (0.00%)  1/983 (0.10%) 
Guillain-Barre syndrome  1  0/990 (0.00%)  1/983 (0.10%) 
Headache  1  3/990 (0.30%)  0/983 (0.00%) 
Ischaemic stroke  1  0/990 (0.00%)  1/983 (0.10%) 
Meralgia paraesthetica  1  1/990 (0.10%)  0/983 (0.00%) 
Neuralgia  1  1/990 (0.10%)  1/983 (0.10%) 
Neuropathy peripheral  1  0/990 (0.00%)  1/983 (0.10%) 
Paraparesis  1  0/990 (0.00%)  1/983 (0.10%) 
Parkinsonism  1  1/990 (0.10%)  0/983 (0.00%) 
Radiculopathy  1  1/990 (0.10%)  1/983 (0.10%) 
Sciatica  1  2/990 (0.20%)  0/983 (0.00%) 
Seizure  1  0/990 (0.00%)  1/983 (0.10%) 
Syncope  1  4/990 (0.40%)  3/983 (0.31%) 
Transient ischaemic attack  1  1/990 (0.10%)  2/983 (0.20%) 
Product Issues     
Device malfunction  1  2/990 (0.20%)  0/983 (0.00%) 
Device occlusion  1  1/990 (0.10%)  0/983 (0.00%) 
Psychiatric disorders     
Depression  1  0/990 (0.00%)  1/983 (0.10%) 
Major depression  1  0/990 (0.00%)  1/983 (0.10%) 
Mental status changes  1  0/990 (0.00%)  1/983 (0.10%) 
Renal and urinary disorders     
Acute kidney injury  1  6/990 (0.61%)  2/983 (0.20%) 
Calculus urethral  1  0/990 (0.00%)  1/983 (0.10%) 
Chronic kidney disease  1  2/990 (0.20%)  0/983 (0.00%) 
End stage renal disease  1  2/990 (0.20%)  0/983 (0.00%) 
Haematuria  1  1/990 (0.10%)  2/983 (0.20%) 
Hydronephrosis  1  1/990 (0.10%)  0/983 (0.00%) 
Nephrolithiasis  1  1/990 (0.10%)  0/983 (0.00%) 
Renal failure  1  0/990 (0.00%)  1/983 (0.10%) 
Tubulointerstitial nephritis  1  1/990 (0.10%)  0/983 (0.00%) 
Ureterolithiasis  1  0/990 (0.00%)  1/983 (0.10%) 
Urethral stenosis  1  1/990 (0.10%)  1/983 (0.10%) 
Urinary incontinence  1  2/990 (0.20%)  0/983 (0.00%) 
Urinary retention  1  1/990 (0.10%)  0/983 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  2/990 (0.20%)  1/983 (0.10%) 
Metrorrhagia  1  1/990 (0.10%)  0/983 (0.00%) 
Postmenopausal haemorrhage  1  1/990 (0.10%)  0/983 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  3/990 (0.30%)  1/983 (0.10%) 
Asthma  1  1/990 (0.10%)  0/983 (0.00%) 
Asthma-chronic obstructive pulmonary disease overlap syndrome  1  0/990 (0.00%)  1/983 (0.10%) 
Chronic obstructive pulmonary disease  1  5/990 (0.51%)  4/983 (0.41%) 
Cough  1  1/990 (0.10%)  0/983 (0.00%) 
Dyspnoea  1  0/990 (0.00%)  2/983 (0.20%) 
Dyspnoea exertional  1  1/990 (0.10%)  1/983 (0.10%) 
Epistaxis  1  1/990 (0.10%)  0/983 (0.00%) 
Pleural effusion  1  1/990 (0.10%)  1/983 (0.10%) 
Pleurisy  1  1/990 (0.10%)  0/983 (0.00%) 
Pneumonia aspiration  1  1/990 (0.10%)  0/983 (0.00%) 
Pneumonitis  1  1/990 (0.10%)  0/983 (0.00%) 
Pneumothorax  1  1/990 (0.10%)  0/983 (0.00%) 
Pulmonary embolism  1  1/990 (0.10%)  1/983 (0.10%) 
Pulmonary mass  1  1/990 (0.10%)  0/983 (0.00%) 
Pulmonary oedema  1  1/990 (0.10%)  1/983 (0.10%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  0/990 (0.00%)  2/983 (0.20%) 
Decubitus ulcer  1  0/990 (0.00%)  1/983 (0.10%) 
Dermal cyst  1  1/990 (0.10%)  0/983 (0.00%) 
Diabetic foot  1  2/990 (0.20%)  1/983 (0.10%) 
Eczema  1  0/990 (0.00%)  1/983 (0.10%) 
Eczema nummular  1  0/990 (0.00%)  1/983 (0.10%) 
Hyperhidrosis  1  0/990 (0.00%)  1/983 (0.10%) 
Psoriasis  1  0/990 (0.00%)  1/983 (0.10%) 
Skin ulcer  1  1/990 (0.10%)  2/983 (0.20%) 
Surgical and medical procedures     
Fracture treatment  1  1/990 (0.10%)  0/983 (0.00%) 
Gastric banding reversal  1  1/990 (0.10%)  0/983 (0.00%) 
Vascular disorders     
Accelerated hypertension  1  0/990 (0.00%)  1/983 (0.10%) 
Aortic aneurysm  1  4/990 (0.40%)  1/983 (0.10%) 
Aortic aneurysm rupture  1  1/990 (0.10%)  0/983 (0.00%) 
Aortic stenosis  1  1/990 (0.10%)  0/983 (0.00%) 
Arterial occlusive disease  1  0/990 (0.00%)  1/983 (0.10%) 
Circulatory collapse  1  1/990 (0.10%)  0/983 (0.00%) 
Deep vein thrombosis  1  0/990 (0.00%)  2/983 (0.20%) 
Hypertension  1  5/990 (0.51%)  7/983 (0.71%) 
Hypertensive crisis  1  0/990 (0.00%)  1/983 (0.10%) 
Hypotension  1  1/990 (0.10%)  3/983 (0.31%) 
Iliac artery occlusion  1  1/990 (0.10%)  0/983 (0.00%) 
Intermittent claudication  1  2/990 (0.20%)  2/983 (0.20%) 
Leriche syndrome  1  1/990 (0.10%)  0/983 (0.00%) 
Peripheral arterial occlusive disease  1  5/990 (0.51%)  10/983 (1.02%) 
Peripheral artery occlusion  1  1/990 (0.10%)  0/983 (0.00%) 
Peripheral artery stenosis  1  4/990 (0.40%)  2/983 (0.20%) 
Peripheral artery thrombosis  1  0/990 (0.00%)  1/983 (0.10%) 
Peripheral ischaemia  1  4/990 (0.40%)  6/983 (0.61%) 
Peripheral vascular disorder  1  1/990 (0.10%)  1/983 (0.10%) 
Subclavian artery stenosis  1  1/990 (0.10%)  0/983 (0.00%) 
Thrombosis  1  2/990 (0.20%)  1/983 (0.10%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Evolocumab
Affected / at Risk (%) Affected / at Risk (%)
Total   257/990 (25.96%)   272/983 (27.67%) 
Infections and infestations     
Nasopharyngitis  1  74/990 (7.47%)  101/983 (10.27%) 
Upper respiratory tract infection  1  63/990 (6.36%)  53/983 (5.39%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  59/990 (5.96%)  45/983 (4.58%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  36/990 (3.64%)  58/983 (5.90%) 
Vascular disorders     
Hypertension  1  66/990 (6.67%)  61/983 (6.21%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
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.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02207634     History of Changes
Other Study ID Numbers: 20130385
2014-001976-75 ( EudraCT Number )
First Submitted: July 31, 2014
First Posted: August 4, 2014
Results First Submitted: December 15, 2017
Results First Posted: January 16, 2018
Last Update Posted: January 16, 2018