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Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With AVE0010 (Lixisenatide) (ELIXA)

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ClinicalTrials.gov Identifier: NCT01147250
Recruitment Status : Completed
First Posted : June 22, 2010
Results First Posted : October 14, 2016
Last Update Posted : December 20, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: Lixisenatide (AVE0010)
Drug: Placebo
Enrollment 6068
Recruitment Details The study was conducted at 829 centers in 49 countries. A total of 7719 participants were screened between June 24, 2010 and July 24, 2013. 1651 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details 7627 participants underwent 1 week placebo run-in period. 1559 were run-in failures due to exclusion criteria met. 6068 participants were randomized 1:1 to lixisenatide and placebo arms in double-blind treatment period. Duration of study was event driven until approximately 844 positively adjudicated primary cardiovascular (CV) outcome events.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description Placebo matched to lixisenatide once daily (QD) subcutaneously (SC) up to end of treatment (median exposure: 23 months). Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment (median exposure: 22 months).
Period Title: Overall Study
Started 3034 3034
Treated 3032 3031
Completed 2924 2929
Not Completed 110 105
Reason Not Completed
Lost to Follow-up             14             11
Withdrawal by Subject             83             88
Site termination by sponsor             13             5
Other than specified             0             1
Arm/Group Title Placebo Lixisenatide Total
Hide Arm/Group Description Placebo matched to lixisenatide QD SC up to end of treatment (median exposure: 23 months). Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment (median exposure: 22 months). Total of all reporting groups
Overall Number of Baseline Participants 3034 3034 6068
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3034 participants 3034 participants 6068 participants
60.6  (9.6) 59.9  (9.7) 60.3  (9.7)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3034 participants 3034 participants 6068 participants
Female
938
  30.9%
923
  30.4%
1861
  30.7%
Male
2096
  69.1%
2111
  69.6%
4207
  69.3%
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3034 participants 3034 participants 6068 participants
Caucasian/White 2318 2258 4576
Black 103 118 221
Asian/Oriental 367 404 771
Other 246 254 500
Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3034 participants 3034 participants 6068 participants
Hispanic 903 865 1768
Not Hispanic 2131 2169 4300
Qualifying Acute Coronary Syndrome (ACS) event  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3034 participants 3034 participants 6068 participants
ST-segment elevation myocardial infarction (MI) 1317 1349 2666
Non ST-segment elevation MI 1183 1165 2348
Unstable angina 528 514 1042
Unclassified 4 5 9
Not qualifying ACS event 2 1 3
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 3034 participants 3034 participants 6068 participants
30.2  (5.79) 30.12  (5.6) 30.16  (5.69)
[1]
Measure Description: N=3032, 3033
Body Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 3034 participants 3034 participants 6068 participants
85.06  (19.64) 84.64  (19.21) 84.85  (19.43)
[1]
Measure Description: N=3032, 3033
Glycosylated Hemoglobin (HbA1c)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of HbA1c
Number Analyzed 3034 participants 3034 participants 6068 participants
7.64  (1.28) 7.72  (1.32) 7.68  (1.30)
[1]
Measure Description: N=3033, 3034
Duration of Diabetes   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3034 participants 3034 participants 6068 participants
9.38  (8.32) 9.2  (8.19) 9.29  (8.25)
[1]
Measure Description: N=3034, 3031
1.Primary Outcome
Title Time to First Occurence of Primary CV Event: CV Death, Non-Fatal MI, Non-Fatal Stroke or Hospitalization for Unstable Angina
Hide Description Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the onset of primary CV endpoint over time. Number of observed participants with endpoint events were reported. A CV event adjudication committee (CAC) reviewed and adjudicated, in a blinded fashion, all potential events.
Time Frame From randomization up to the end of study (median follow-up of 25 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population defined as all randomized participants analyzed according to the treatment group allocated at randomization.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
Placebo matched to lixisenatide QD SC up to end of treatment (median exposure: 23 months).
Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment (median exposure: 22 months).
Overall Number of Participants Analyzed 3034 3034
Measure Type: Number
Unit of Measure: participants
399 406
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lixisenatide
Comments Analysis was performed using Cox proportional hazards model with treatment groups, and region (North America, South and Central America, Western Europe, Eastern Europe, Africa/Near East, and Asia/Pacific) as covariates, and the associated two-sided 95% confidence interval (CI).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority of lixisenatide versus placebo was to be claimed if the upper bound of the 2-sided 95% CI of the hazard ratio was <1.3.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.017
Confidence Interval (2-Sided) 95%
0.886 to 1.168
Estimation Comments Lixisenatide vs Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lixisenatide
Comments Analysis was performed using Cox proportional hazards model with treatment groups, and region (North America, South and Central America, Western Europe, Eastern Europe, Africa/Near East, and Asia/Pacific) as covariates, and the associated two-sided 95% CI. Superiority of lixisenatide versus placebo was to be claimed if the upper bound of the 2-sided 95% CI of the hazard ratio was <1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8542
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.017
Confidence Interval (2-Sided) 95%
0.886 to 1.168
Estimation Comments Lixisenatide vs Placebo
2.Secondary Outcome
Title Time to First Occurence of CV Event: CV Death, Non-Fatal MI, Non-Fatal Stroke, Hospitalization for Unstable Angina or Hospitalization For Heart Failure
Hide Description All CV events were positively adjudicated by the CAC, used in the analysis of the composite CV endpoint comprised of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure. Number of observed participants with endpoint events were reported.
Time Frame From randomization up to the end of study (median follow-up of 25 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
Placebo matched to lixisenatide QD SC up to end of treatment (median exposure: 23 months).
Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment (median exposure: 22 months).
Overall Number of Participants Analyzed 3034 3034
Measure Type: Number
Unit of Measure: participants
469 456
3.Secondary Outcome
Title Time to First Occurence of CV Event: CV Death, Non-Fatal MI, Non-Fatal Stroke, Hospitalization for Unstable Angina, Hospitalization For Heart Failure or Coronary Revascularization Procedure
Hide Description All CV events were positively adjudicated by CAC, used in the analysis of the composite CV endpoint comprised of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization procedure. Number of observed participants with endpoint events were reported.
Time Frame From randomization up to the end of study (median follow-up of 25 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
Placebo matched to lixisenatide QD SC up to end of treatment (median exposure: 23 months).
Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment (median exposure: 22 months).
Overall Number of Participants Analyzed 3034 3034
Measure Type: Number
Unit of Measure: participants
659 661
4.Secondary Outcome
Title Percent Change From Baseline in the Urinary Albumin/Creatinine Ratio (UACR) at Week 108
Hide Description Presence of albumin in urine is a marker of nephropathy, an important microvascular complication of diabetes. UACR was defined as the ratio: mg of albumin per gram of creatinine. UACR data were log transformed before the analysis. Calculation was based on geometric mean.
Time Frame Baseline to Week 108 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline UACR value. Missing data was imputed using last observation carried forward (LOCF) using the last available post-baseline UACR before Week 108 as the value at Week 108, regardless of treatment discontinuation or not.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
Placebo matched to lixisenatide QD SC up to end of treatment (median exposure: 23 months).
Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment (median exposure: 22 months).
Overall Number of Participants Analyzed 2830 2803
Geometric Mean (Standard Error)
Unit of Measure: percent change
34.21  (3.09) 24.17  (2.84)
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to study end (maximum follow-up of 52 months) regardless of seriousness or relationship to investigational medicinal product (IMP). Cardiovascular efficacy endpoint events were collected and analyzed separately within same time frame.
Adverse Event Reporting Description Reported AEs are treatment emergent AEs that developed/worsened during ‘on treatment period’ (time from first administration of IMP up to 3 days after the last administration of IMP). Analysis was done on safety population that included all randomized participants received at least one dose of IMP.
 
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description Participants exposed to Placebo matched to lixisenatide QD. (Median exposure: 23 months) Participants exposed to Lixisenatide 10 mcg QD SC for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to 225 weeks. (Median exposure: 22 months)
All-Cause Mortality
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   669/3032 (22.06%)   625/3031 (20.62%) 
Blood and lymphatic system disorders     
Anaemia  1  9/3032 (0.30%)  8/3031 (0.26%) 
Coagulopathy  1  0/3032 (0.00%)  1/3031 (0.03%) 
Haemorrhagic anaemia  1  2/3032 (0.07%)  1/3031 (0.03%) 
Increased tendency to bruise  1  0/3032 (0.00%)  1/3031 (0.03%) 
Iron deficiency anaemia  1  1/3032 (0.03%)  1/3031 (0.03%) 
Neutropenia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pernicious anaemia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Nephrogenic anaemia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Normochromic normocytic anaemia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Thrombocytopenia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Cardiac disorders     
Angina pectoris  1  23/3032 (0.76%)  23/3031 (0.76%) 
Atrial fibrillation  1  30/3032 (0.99%)  23/3031 (0.76%) 
Ventricular tachycardia  1  8/3032 (0.26%)  9/3031 (0.30%) 
Coronary artery disease  1  5/3032 (0.16%)  4/3031 (0.13%) 
Atrial flutter  1  5/3032 (0.16%)  3/3031 (0.10%) 
Arrhythmia  1  1/3032 (0.03%)  2/3031 (0.07%) 
Atrioventricular block  1  0/3032 (0.00%)  2/3031 (0.07%) 
Atrioventricular block complete  1  8/3032 (0.26%)  2/3031 (0.07%) 
Bradycardia  1  5/3032 (0.16%)  2/3031 (0.07%) 
Cardiac arrest  1  1/3032 (0.03%)  2/3031 (0.07%) 
Myocarditis  1  0/3032 (0.00%)  2/3031 (0.07%) 
Ventricular extrasystoles  1  3/3032 (0.10%)  2/3031 (0.07%) 
Atrioventricular block first degree  1  0/3032 (0.00%)  1/3031 (0.03%) 
Atrioventricular block second degree  1  1/3032 (0.03%)  1/3031 (0.03%) 
Bifascicular block  1  0/3032 (0.00%)  1/3031 (0.03%) 
Cardio-respiratory arrest  1  2/3032 (0.07%)  1/3031 (0.03%) 
Hypertensive heart disease  1  0/3032 (0.00%)  1/3031 (0.03%) 
Intracardiac thrombus  1  0/3032 (0.00%)  1/3031 (0.03%) 
Mitral valve incompetence  1  1/3032 (0.03%)  1/3031 (0.03%) 
Myocardial ischaemia  1  3/3032 (0.10%)  1/3031 (0.03%) 
Palpitations  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pericardial effusion  1  3/3032 (0.10%)  1/3031 (0.03%) 
Pericarditis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Sick sinus syndrome  1  5/3032 (0.16%)  1/3031 (0.03%) 
Supraventricular tachycardia  1  4/3032 (0.13%)  1/3031 (0.03%) 
Tachycardia  1  1/3032 (0.03%)  1/3031 (0.03%) 
Arteriosclerosis coronary artery  1  1/3032 (0.03%)  0/3031 (0.00%) 
Atrial tachycardia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Coronary artery occlusion  1  1/3032 (0.03%)  0/3031 (0.00%) 
Ischaemic cardiomyopathy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Left ventricular dysfunction  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pericardial haemorrhage  1  1/3032 (0.03%)  0/3031 (0.00%) 
Tachyarrhythmia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Trifascicular block  1  2/3032 (0.07%)  0/3031 (0.00%) 
Ear and labyrinth disorders     
Deafness neurosensory  1  0/3032 (0.00%)  3/3031 (0.10%) 
Sudden hearing loss  1  0/3032 (0.00%)  1/3031 (0.03%) 
Vertigo positional  1  1/3032 (0.03%)  1/3031 (0.03%) 
Vertigo  1  2/3032 (0.07%)  0/3031 (0.00%) 
Vertigo labyrinthine  1  1/3032 (0.03%)  0/3031 (0.00%) 
Endocrine disorders     
Goitre  1  1/3032 (0.03%)  1/3031 (0.03%) 
Hyperparathyroidism  1  1/3032 (0.03%)  1/3031 (0.03%) 
Hyperthyroidism  1  1/3032 (0.03%)  0/3031 (0.00%) 
Eye disorders     
Cataract  1  5/3032 (0.16%)  4/3031 (0.13%) 
Cataract nuclear  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diabetic retinal oedema  1  0/3032 (0.00%)  1/3031 (0.03%) 
Glaucoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Ophthalmoplegia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Vitreous haemorrhage  1  3/3032 (0.10%)  1/3031 (0.03%) 
Amaurosis fugax  1  1/3032 (0.03%)  0/3031 (0.00%) 
Angle closure glaucoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Arteriosclerotic retinopathy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Blindness unilateral  1  1/3032 (0.03%)  0/3031 (0.00%) 
Diabetic eye disease  1  1/3032 (0.03%)  0/3031 (0.00%) 
Open angle glaucoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Retinal detachment  1  1/3032 (0.03%)  0/3031 (0.00%) 
Uveitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gastrointestinal disorders     
Gastritis  1  4/3032 (0.13%)  7/3031 (0.23%) 
Inguinal hernia  1  3/3032 (0.10%)  5/3031 (0.16%) 
Duodenal ulcer  1  3/3032 (0.10%)  4/3031 (0.13%) 
Upper gastrointestinal haemorrhage  1  4/3032 (0.13%)  4/3031 (0.13%) 
Diarrhoea  1  4/3032 (0.13%)  3/3031 (0.10%) 
Gastrooesophageal reflux disease  1  1/3032 (0.03%)  3/3031 (0.10%) 
Lower gastrointestinal haemorrhage  1  3/3032 (0.10%)  3/3031 (0.10%) 
Abdominal pain  1  7/3032 (0.23%)  2/3031 (0.07%) 
Abdominal pain upper  1  2/3032 (0.07%)  2/3031 (0.07%) 
Epigastric discomfort  1  0/3032 (0.00%)  2/3031 (0.07%) 
Gastric ulcer  1  2/3032 (0.07%)  2/3031 (0.07%) 
Gastric ulcer haemorrhage  1  2/3032 (0.07%)  2/3031 (0.07%) 
Gastrointestinal haemorrhage  1  6/3032 (0.20%)  2/3031 (0.07%) 
Ileus  1  0/3032 (0.00%)  2/3031 (0.07%) 
Intestinal ischaemia  1  0/3032 (0.00%)  2/3031 (0.07%) 
Large intestine polyp  1  1/3032 (0.03%)  2/3031 (0.07%) 
Mallory-Weiss syndrome  1  0/3032 (0.00%)  2/3031 (0.07%) 
Pancreatitis  1  3/3032 (0.10%)  2/3031 (0.07%) 
Umbilical hernia  1  1/3032 (0.03%)  2/3031 (0.07%) 
Vomiting  1  0/3032 (0.00%)  2/3031 (0.07%) 
Abdominal adhesions  1  0/3032 (0.00%)  1/3031 (0.03%) 
Abdominal rigidity  1  0/3032 (0.00%)  1/3031 (0.03%) 
Abdominal wall haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Chronic gastritis  1  2/3032 (0.07%)  1/3031 (0.03%) 
Diabetic gastroparesis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diverticular perforation  1  1/3032 (0.03%)  1/3031 (0.03%) 
Duodenal ulcer haemorrhage  1  2/3032 (0.07%)  1/3031 (0.03%) 
Dyspepsia  1  1/3032 (0.03%)  1/3031 (0.03%) 
Dysphagia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Faecal vomiting  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gastroduodenitis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gingival bleeding  1  0/3032 (0.00%)  1/3031 (0.03%) 
Intestinal haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Large intestine perforation  1  1/3032 (0.03%)  1/3031 (0.03%) 
Melaena  1  2/3032 (0.07%)  1/3031 (0.03%) 
Oesophageal ulcer  1  1/3032 (0.03%)  1/3031 (0.03%) 
Oesophagitis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pancreatitis chronic  1  0/3032 (0.00%)  1/3031 (0.03%) 
Rectal haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Small intestinal ulcer haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Umbilical hernia, obstructive  1  0/3032 (0.00%)  1/3031 (0.03%) 
Abdominal distension  1  1/3032 (0.03%)  0/3031 (0.00%) 
Abdominal hernia  1  2/3032 (0.07%)  0/3031 (0.00%) 
Abdominal incarcerated hernia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Anal fistula  1  1/3032 (0.03%)  0/3031 (0.00%) 
Colitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Constipation  1  1/3032 (0.03%)  0/3031 (0.00%) 
Crohn's disease  1  1/3032 (0.03%)  0/3031 (0.00%) 
Diverticulum  1  1/3032 (0.03%)  0/3031 (0.00%) 
Duodenitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Food poisoning  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gastric disorder  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gastric polyps  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gastritis erosive  1  3/3032 (0.10%)  0/3031 (0.00%) 
Gastritis haemorrhagic  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gastroduodenitis haemorrhagic  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gastrointestinal disorder  1  1/3032 (0.03%)  0/3031 (0.00%) 
Haematemesis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Haemorrhoidal haemorrhage  1  1/3032 (0.03%)  0/3031 (0.00%) 
Haemorrhoids  1  1/3032 (0.03%)  0/3031 (0.00%) 
Impaired gastric emptying  1  1/3032 (0.03%)  0/3031 (0.00%) 
Intestinal obstruction  1  1/3032 (0.03%)  0/3031 (0.00%) 
Nausea  1  3/3032 (0.10%)  0/3031 (0.00%) 
Obstruction gastric  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pancreatitis acute  1  2/3032 (0.07%)  0/3031 (0.00%) 
Peritoneal haemorrhage  1  1/3032 (0.03%)  0/3031 (0.00%) 
General disorders     
Non-cardiac chest pain  1  42/3032 (1.39%)  46/3031 (1.52%) 
Chest pain  1  0/3032 (0.00%)  3/3031 (0.10%) 
Death  1  2/3032 (0.07%)  3/3031 (0.10%) 
Coronary artery restenosis  1  2/3032 (0.07%)  2/3031 (0.07%) 
Arterial restenosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Asthenia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gait disturbance  1  0/3032 (0.00%)  1/3031 (0.03%) 
Impaired healing  1  0/3032 (0.00%)  1/3031 (0.03%) 
Malaise  1  2/3032 (0.07%)  1/3031 (0.03%) 
Multi-organ failure  1  1/3032 (0.03%)  1/3031 (0.03%) 
Polyp  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pyrexia  1  1/3032 (0.03%)  1/3031 (0.03%) 
Sudden death  1  0/3032 (0.00%)  1/3031 (0.03%) 
Thrombosis in device  1  0/3032 (0.00%)  1/3031 (0.03%) 
Chest discomfort  1  1/3032 (0.03%)  0/3031 (0.00%) 
Implant site extravasation  1  1/3032 (0.03%)  0/3031 (0.00%) 
Inflammation  1  1/3032 (0.03%)  0/3031 (0.00%) 
Local swelling  1  1/3032 (0.03%)  0/3031 (0.00%) 
Oedema peripheral  1  2/3032 (0.07%)  0/3031 (0.00%) 
Pain  1  1/3032 (0.03%)  0/3031 (0.00%) 
Systemic inflammatory response syndrome  1  1/3032 (0.03%)  0/3031 (0.00%) 
Vessel puncture site haematoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  6/3032 (0.20%)  13/3031 (0.43%) 
Cholecystitis acute  1  7/3032 (0.23%)  10/3031 (0.33%) 
Cholecystitis  1  5/3032 (0.16%)  9/3031 (0.30%) 
Bile duct stone  1  1/3032 (0.03%)  1/3031 (0.03%) 
Cholecystitis chronic  1  1/3032 (0.03%)  1/3031 (0.03%) 
Gallbladder polyp  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hepatic cirrhosis  1  2/3032 (0.07%)  1/3031 (0.03%) 
Hepatic function abnormal  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hepatitis acute  1  0/3032 (0.00%)  1/3031 (0.03%) 
Cholangitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Cholestasis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Drug-induced liver injury  1  2/3032 (0.07%)  0/3031 (0.00%) 
Ischaemic hepatitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Liver injury  1  1/3032 (0.03%)  0/3031 (0.00%) 
Immune system disorders     
Anaphylactic shock  1  0/3032 (0.00%)  3/3031 (0.10%) 
Drug hypersensitivity  1  1/3032 (0.03%)  1/3031 (0.03%) 
Anaphylactic reaction  1  1/3032 (0.03%)  0/3031 (0.00%) 
Infections and infestations     
Pneumonia  1  51/3032 (1.68%)  36/3031 (1.19%) 
Urinary tract infection  1  19/3032 (0.63%)  18/3031 (0.59%) 
Cellulitis  1  18/3032 (0.59%)  17/3031 (0.56%) 
Gastroenteritis  1  9/3032 (0.30%)  13/3031 (0.43%) 
Sepsis  1  10/3032 (0.33%)  8/3031 (0.26%) 
Bronchopneumonia  1  2/3032 (0.07%)  6/3031 (0.20%) 
Respiratory tract infection  1  4/3032 (0.13%)  6/3031 (0.20%) 
Bronchitis  1  2/3032 (0.07%)  5/3031 (0.16%) 
Osteomyelitis  1  9/3032 (0.30%)  4/3031 (0.13%) 
Anal abscess  1  2/3032 (0.07%)  3/3031 (0.10%) 
Appendicitis  1  3/3032 (0.10%)  3/3031 (0.10%) 
Diverticulitis  1  1/3032 (0.03%)  3/3031 (0.10%) 
Erysipelas  1  7/3032 (0.23%)  3/3031 (0.10%) 
Lower respiratory tract infection  1  3/3032 (0.10%)  3/3031 (0.10%) 
Post procedural infection  1  1/3032 (0.03%)  3/3031 (0.10%) 
Postoperative wound infection  1  5/3032 (0.16%)  3/3031 (0.10%) 
Pyelonephritis  1  4/3032 (0.13%)  3/3031 (0.10%) 
Upper respiratory tract infection  1  3/3032 (0.10%)  3/3031 (0.10%) 
Abdominal sepsis  1  1/3032 (0.03%)  2/3031 (0.07%) 
Diabetic foot infection  1  0/3032 (0.00%)  2/3031 (0.07%) 
Empyema  1  0/3032 (0.00%)  2/3031 (0.07%) 
Gangrene  1  7/3032 (0.23%)  2/3031 (0.07%) 
Gastroenteritis viral  1  0/3032 (0.00%)  2/3031 (0.07%) 
Infected skin ulcer  1  0/3032 (0.00%)  2/3031 (0.07%) 
Infective exacerbation of chronic obstructive airways disease  1  0/3032 (0.00%)  2/3031 (0.07%) 
Lobar pneumonia  1  1/3032 (0.03%)  2/3031 (0.07%) 
Pyelonephritis chronic  1  1/3032 (0.03%)  2/3031 (0.07%) 
Septic shock  1  3/3032 (0.10%)  2/3031 (0.07%) 
Tooth abscess  1  0/3032 (0.00%)  2/3031 (0.07%) 
Urosepsis  1  2/3032 (0.07%)  2/3031 (0.07%) 
Wound infection  1  2/3032 (0.07%)  2/3031 (0.07%) 
Arthritis infective  1  0/3032 (0.00%)  1/3031 (0.03%) 
Bacteraemia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Bone abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
Bronchitis viral  1  0/3032 (0.00%)  1/3031 (0.03%) 
Chronic sinusitis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Clostridium difficile colitis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Colonic abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
Device related infection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diarrhoea infectious  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gallbladder abscess  1  1/3032 (0.03%)  1/3031 (0.03%) 
Gastritis viral  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gastroenteritis clostridial  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gastrointestinal infection  1  1/3032 (0.03%)  1/3031 (0.03%) 
Groin abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
H1N1 influenza  1  0/3032 (0.00%)  1/3031 (0.03%) 
Helicobacter gastritis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Infected bites  1  0/3032 (0.00%)  1/3031 (0.03%) 
Influenza  1  1/3032 (0.03%)  1/3031 (0.03%) 
Lung infection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Mediastinitis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Meningitis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Mycobacterial infection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Nail bed infection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Osteomyelitis fungal  1  0/3032 (0.00%)  1/3031 (0.03%) 
Paraspinal abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
Paronychia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Peritonitis  1  2/3032 (0.07%)  1/3031 (0.03%) 
Pilonidal cyst  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pneumonia bacterial  1  1/3032 (0.03%)  1/3031 (0.03%) 
Pulmonary tuberculosis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Puncture site abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pyelonephritis acute  1  4/3032 (0.13%)  1/3031 (0.03%) 
Renal abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
Scrotal abscess  1  0/3032 (0.00%)  1/3031 (0.03%) 
Soft tissue infection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Staphylococcal infection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Subcutaneous abscess  1  3/3032 (0.10%)  1/3031 (0.03%) 
Toxoplasmosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Viral infection  1  1/3032 (0.03%)  1/3031 (0.03%) 
Abdominal abscess  1  1/3032 (0.03%)  0/3031 (0.00%) 
Abdominal wall infection  1  1/3032 (0.03%)  0/3031 (0.00%) 
Abscess limb  1  3/3032 (0.10%)  0/3031 (0.00%) 
Amoebic dysentery  1  1/3032 (0.03%)  0/3031 (0.00%) 
Appendicitis perforated  1  1/3032 (0.03%)  0/3031 (0.00%) 
Bacterial pyelonephritis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Bronchitis bacterial  1  1/3032 (0.03%)  0/3031 (0.00%) 
Burn infection  1  1/3032 (0.03%)  0/3031 (0.00%) 
Carbuncle  1  1/3032 (0.03%)  0/3031 (0.00%) 
Cat scratch disease  1  1/3032 (0.03%)  0/3031 (0.00%) 
Chronic hepatitis B  1  1/3032 (0.03%)  0/3031 (0.00%) 
Chronic hepatitis C  1  1/3032 (0.03%)  0/3031 (0.00%) 
Dengue fever  1  2/3032 (0.07%)  0/3031 (0.00%) 
Endocarditis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Haematoma infection  1  1/3032 (0.03%)  0/3031 (0.00%) 
Klebsiella sepsis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Liver abscess  1  1/3032 (0.03%)  0/3031 (0.00%) 
Localised infection  1  4/3032 (0.13%)  0/3031 (0.00%) 
Nasopharyngitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Osteomyelitis acute  1  1/3032 (0.03%)  0/3031 (0.00%) 
Osteomyelitis chronic  1  2/3032 (0.07%)  0/3031 (0.00%) 
Otitis media chronic  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pleurisy viral  1  1/3032 (0.03%)  0/3031 (0.00%) 
Psoas abscess  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pulmonary sepsis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Staphylococcal osteomyelitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Subdiaphragmatic abscess  1  1/3032 (0.03%)  0/3031 (0.00%) 
Tick-borne fever  1  1/3032 (0.03%)  0/3031 (0.00%) 
Viral corneal ulcer  1  1/3032 (0.03%)  0/3031 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  7/3032 (0.23%)  7/3031 (0.23%) 
Ankle fracture  1  3/3032 (0.10%)  2/3031 (0.07%) 
Femur fracture  1  3/3032 (0.10%)  2/3031 (0.07%) 
Head injury  1  2/3032 (0.07%)  2/3031 (0.07%) 
Postoperative thoracic procedure complication  1  1/3032 (0.03%)  2/3031 (0.07%) 
Toxicity to various agents  1  2/3032 (0.07%)  2/3031 (0.07%) 
Vascular pseudoaneurysm  1  0/3032 (0.00%)  2/3031 (0.07%) 
Accidental overdose  1  0/3032 (0.00%)  1/3031 (0.03%) 
Allergic transfusion reaction  1  0/3032 (0.00%)  1/3031 (0.03%) 
Arthropod sting  1  0/3032 (0.00%)  1/3031 (0.03%) 
Brain contusion  1  1/3032 (0.03%)  1/3031 (0.03%) 
Chest injury  1  0/3032 (0.00%)  1/3031 (0.03%) 
Contusion  1  1/3032 (0.03%)  1/3031 (0.03%) 
Femoral neck fracture  1  0/3032 (0.00%)  1/3031 (0.03%) 
Foot fracture  1  0/3032 (0.00%)  1/3031 (0.03%) 
Forearm fracture  1  0/3032 (0.00%)  1/3031 (0.03%) 
Foreign body  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gun shot wound  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hand fracture  1  2/3032 (0.07%)  1/3031 (0.03%) 
Hip fracture  1  8/3032 (0.26%)  1/3031 (0.03%) 
Humerus fracture  1  3/3032 (0.10%)  1/3031 (0.03%) 
Incision site haematoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Incisional hernia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Joint injury  1  0/3032 (0.00%)  1/3031 (0.03%) 
Limb injury  1  0/3032 (0.00%)  1/3031 (0.03%) 
Lower limb fracture  1  1/3032 (0.03%)  1/3031 (0.03%) 
Lumbar vertebral fracture  1  0/3032 (0.00%)  1/3031 (0.03%) 
Post procedural complication  1  0/3032 (0.00%)  1/3031 (0.03%) 
Post procedural haematoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pubis fracture  1  0/3032 (0.00%)  1/3031 (0.03%) 
Rib fracture  1  2/3032 (0.07%)  1/3031 (0.03%) 
Scar  1  0/3032 (0.00%)  1/3031 (0.03%) 
Spinal fracture  1  0/3032 (0.00%)  1/3031 (0.03%) 
Sports injury  1  0/3032 (0.00%)  1/3031 (0.03%) 
Subdural haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Tibia fracture  1  1/3032 (0.03%)  1/3031 (0.03%) 
Acetabulum fracture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Alcohol poisoning  1  1/3032 (0.03%)  0/3031 (0.00%) 
Cartilage injury  1  1/3032 (0.03%)  0/3031 (0.00%) 
Concussion  1  1/3032 (0.03%)  0/3031 (0.00%) 
Craniocerebral injury  1  1/3032 (0.03%)  0/3031 (0.00%) 
Fibula fracture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Joint dislocation  1  1/3032 (0.03%)  0/3031 (0.00%) 
Ligament rupture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Ligament sprain  1  1/3032 (0.03%)  0/3031 (0.00%) 
Medication error  1  1/3032 (0.03%)  0/3031 (0.00%) 
Meniscus injury  1  1/3032 (0.03%)  0/3031 (0.00%) 
Multiple injuries  1  1/3032 (0.03%)  0/3031 (0.00%) 
Post procedural discharge  1  1/3032 (0.03%)  0/3031 (0.00%) 
Post procedural haemorrhage  1  1/3032 (0.03%)  0/3031 (0.00%) 
Postoperative fever  1  1/3032 (0.03%)  0/3031 (0.00%) 
Procedural pain  1  2/3032 (0.07%)  0/3031 (0.00%) 
Radius fracture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Scrotal haematoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Skull fracture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Soft tissue injury  1  1/3032 (0.03%)  0/3031 (0.00%) 
Subdural haematoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Ulna fracture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Wound haemorrhage  1  1/3032 (0.03%)  0/3031 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  7/3032 (0.23%)  2/3031 (0.07%) 
Blood creatinine increased  1  0/3032 (0.00%)  1/3031 (0.03%) 
Blood glucose fluctuation  1  0/3032 (0.00%)  1/3031 (0.03%) 
Blood glucose increased  1  4/3032 (0.13%)  1/3031 (0.03%) 
Blood pressure increased  1  1/3032 (0.03%)  1/3031 (0.03%) 
Carbohydrate antigen 19-9 increased  1  0/3032 (0.00%)  1/3031 (0.03%) 
Cardiac pacemaker evaluation  1  0/3032 (0.00%)  1/3031 (0.03%) 
Crystal urine present  1  0/3032 (0.00%)  1/3031 (0.03%) 
Electrocardiogram abnormal  1  0/3032 (0.00%)  1/3031 (0.03%) 
Prostatic specific antigen increased  1  0/3032 (0.00%)  1/3031 (0.03%) 
Angiogram  1  1/3032 (0.03%)  0/3031 (0.00%) 
Blood glucose abnormal  1  1/3032 (0.03%)  0/3031 (0.00%) 
Blood sodium decreased  1  1/3032 (0.03%)  0/3031 (0.00%) 
Catheterisation cardiac  1  1/3032 (0.03%)  0/3031 (0.00%) 
Glycosylated haemoglobin increased  1  2/3032 (0.07%)  0/3031 (0.00%) 
Urine output decreased  1  1/3032 (0.03%)  0/3031 (0.00%) 
Weight decreased  1  1/3032 (0.03%)  0/3031 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  18/3032 (0.59%)  8/3031 (0.26%) 
Hyperkalaemia  1  4/3032 (0.13%)  5/3031 (0.16%) 
Hypoglycaemia  1  10/3032 (0.33%)  5/3031 (0.16%) 
Hyponatraemia  1  4/3032 (0.13%)  5/3031 (0.16%) 
Hyperglycaemia  1  7/3032 (0.23%)  4/3031 (0.13%) 
Dehydration  1  2/3032 (0.07%)  2/3031 (0.07%) 
Hypokalaemia  1  1/3032 (0.03%)  2/3031 (0.07%) 
Decreased appetite  1  0/3032 (0.00%)  1/3031 (0.03%) 
Electrolyte imbalance  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hypovolaemia  1  1/3032 (0.03%)  1/3031 (0.03%) 
Metabolic acidosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diabetic ketoacidosis  1  4/3032 (0.13%)  0/3031 (0.00%) 
Diabetic metabolic decompensation  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gout  1  1/3032 (0.03%)  0/3031 (0.00%) 
Hyperglycaemic hyperosmolar nonketotic syndrome  1  1/3032 (0.03%)  0/3031 (0.00%) 
Hypocalcaemia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Malnutrition  1  1/3032 (0.03%)  0/3031 (0.00%) 
Obesity  1  1/3032 (0.03%)  0/3031 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  4/3032 (0.13%)  4/3031 (0.13%) 
Osteoarthritis  1  7/3032 (0.23%)  3/3031 (0.10%) 
Spinal osteoarthritis  1  0/3032 (0.00%)  3/3031 (0.10%) 
Arthralgia  1  3/3032 (0.10%)  2/3031 (0.07%) 
Fracture malunion  1  0/3032 (0.00%)  2/3031 (0.07%) 
Intervertebral disc protrusion  1  3/3032 (0.10%)  2/3031 (0.07%) 
Musculoskeletal chest pain  1  3/3032 (0.10%)  2/3031 (0.07%) 
Musculoskeletal pain  1  1/3032 (0.03%)  2/3031 (0.07%) 
Rotator cuff syndrome  1  0/3032 (0.00%)  2/3031 (0.07%) 
Arthritis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Coccydynia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Haemarthrosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Joint instability  1  0/3032 (0.00%)  1/3031 (0.03%) 
Lumbar spinal stenosis  1  2/3032 (0.07%)  1/3031 (0.03%) 
Musculoskeletal discomfort  1  1/3032 (0.03%)  1/3031 (0.03%) 
Osteitis  1  2/3032 (0.07%)  1/3031 (0.03%) 
Pain in extremity  1  1/3032 (0.03%)  1/3031 (0.03%) 
Periarthritis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Rhabdomyolysis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Rheumatoid arthritis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Spinal column stenosis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Systemic lupus erythematosus  1  0/3032 (0.00%)  1/3031 (0.03%) 
Bone pain  1  1/3032 (0.03%)  0/3031 (0.00%) 
Dupuytren's contracture  1  1/3032 (0.03%)  0/3031 (0.00%) 
Fasciitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Foot deformity  1  3/3032 (0.10%)  0/3031 (0.00%) 
Myalgia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pain in jaw  1  1/3032 (0.03%)  0/3031 (0.00%) 
Trigger finger  1  1/3032 (0.03%)  0/3031 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1  7/3032 (0.23%)  10/3031 (0.33%) 
Adenocarcinoma of colon  1  2/3032 (0.07%)  6/3031 (0.20%) 
Breast cancer  1  1/3032 (0.03%)  3/3031 (0.10%) 
Bladder cancer  1  4/3032 (0.13%)  2/3031 (0.07%) 
Brain neoplasm  1  0/3032 (0.00%)  2/3031 (0.07%) 
Colon cancer  1  3/3032 (0.10%)  2/3031 (0.07%) 
Hepatocellular carcinoma  1  1/3032 (0.03%)  2/3031 (0.07%) 
Ovarian cancer  1  0/3032 (0.00%)  2/3031 (0.07%) 
Rectal cancer  1  0/3032 (0.00%)  2/3031 (0.07%) 
Renal cancer  1  1/3032 (0.03%)  2/3031 (0.07%) 
Small cell lung cancer  1  1/3032 (0.03%)  2/3031 (0.07%) 
Squamous cell carcinoma of skin  1  1/3032 (0.03%)  2/3031 (0.07%) 
Adenocarcinoma gastric  1  0/3032 (0.00%)  1/3031 (0.03%) 
Benign neoplasm  1  0/3032 (0.00%)  1/3031 (0.03%) 
Benign renal neoplasm  1  0/3032 (0.00%)  1/3031 (0.03%) 
Benign salivary gland neoplasm  1  0/3032 (0.00%)  1/3031 (0.03%) 
Benign small intestinal neoplasm  1  0/3032 (0.00%)  1/3031 (0.03%) 
Bronchial carcinoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Chronic lymphocytic leukaemia  1  1/3032 (0.03%)  1/3031 (0.03%) 
Colon cancer metastatic  1  0/3032 (0.00%)  1/3031 (0.03%) 
Colon cancer recurrent  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diffuse large B-cell lymphoma  1  1/3032 (0.03%)  1/3031 (0.03%) 
Endometrial cancer  1  0/3032 (0.00%)  1/3031 (0.03%) 
Gastric cancer  1  1/3032 (0.03%)  1/3031 (0.03%) 
Gastric cancer stage IV  1  0/3032 (0.00%)  1/3031 (0.03%) 
Glioblastoma multiforme  1  0/3032 (0.00%)  1/3031 (0.03%) 
Iris melanoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Keratoacanthoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Lip squamous cell carcinoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Lung adenocarcinoma  1  1/3032 (0.03%)  1/3031 (0.03%) 
Malignant melanoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Malignant pleural effusion  1  0/3032 (0.00%)  1/3031 (0.03%) 
Meningioma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Metastases to liver  1  0/3032 (0.00%)  1/3031 (0.03%) 
Metastases to pancreas  1  0/3032 (0.00%)  1/3031 (0.03%) 
Metastatic pain  1  0/3032 (0.00%)  1/3031 (0.03%) 
Non-Hodgkin's lymphoma  1  1/3032 (0.03%)  1/3031 (0.03%) 
Ovarian cancer stage III  1  0/3032 (0.00%)  1/3031 (0.03%) 
Ovarian epithelial cancer  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pancreatic carcinoma metastatic  1  1/3032 (0.03%)  1/3031 (0.03%) 
Papillary thyroid cancer  1  1/3032 (0.03%)  1/3031 (0.03%) 
Phaeochromocytoma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pharyngeal cancer  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pituitary tumour benign  1  0/3032 (0.00%)  1/3031 (0.03%) 
Plasma cell myeloma  1  0/3032 (0.00%)  1/3031 (0.03%) 
Prostate cancer metastatic  1  1/3032 (0.03%)  1/3031 (0.03%) 
Prostate cancer stage I  1  0/3032 (0.00%)  1/3031 (0.03%) 
Prostatic adenoma  1  1/3032 (0.03%)  1/3031 (0.03%) 
Rectal adenocarcinoma  1  1/3032 (0.03%)  1/3031 (0.03%) 
Renal cancer metastatic  1  0/3032 (0.00%)  1/3031 (0.03%) 
Retroperitoneal neoplasm  1  0/3032 (0.00%)  1/3031 (0.03%) 
Small cell lung cancer metastatic  1  0/3032 (0.00%)  1/3031 (0.03%) 
Squamous cell carcinoma  1  1/3032 (0.03%)  1/3031 (0.03%) 
Squamous cell carcinoma of lung  1  0/3032 (0.00%)  1/3031 (0.03%) 
Adenocarcinoma pancreas  1  1/3032 (0.03%)  0/3031 (0.00%) 
Adenosquamous cell lung cancer  1  1/3032 (0.03%)  0/3031 (0.00%) 
B-cell lymphoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
B-cell unclassifiable lymphoma low grade  1  1/3032 (0.03%)  0/3031 (0.00%) 
Basal cell carcinoma  1  5/3032 (0.16%)  0/3031 (0.00%) 
Bladder neoplasm  1  1/3032 (0.03%)  0/3031 (0.00%) 
Breast neoplasm  1  1/3032 (0.03%)  0/3031 (0.00%) 
Clear cell renal cell carcinoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Colon adenoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Colon neoplasm  1  2/3032 (0.07%)  0/3031 (0.00%) 
Colorectal adenocarcinoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Fibromatosis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Gallbladder cancer  1  1/3032 (0.03%)  0/3031 (0.00%) 
Lipoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Lung cancer metastatic  1  1/3032 (0.03%)  0/3031 (0.00%) 
Lung neoplasm malignant  1  1/3032 (0.03%)  0/3031 (0.00%) 
Lymphoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Metastases to central nervous system  1  1/3032 (0.03%)  0/3031 (0.00%) 
Metastases to lung  1  1/3032 (0.03%)  0/3031 (0.00%) 
Non-small cell lung cancer  1  2/3032 (0.07%)  0/3031 (0.00%) 
Pancreatic carcinoma  1  3/3032 (0.10%)  0/3031 (0.00%) 
Rectal adenoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Renal cell carcinoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Salivary gland neoplasm  1  1/3032 (0.03%)  0/3031 (0.00%) 
Skin cancer  1  1/3032 (0.03%)  0/3031 (0.00%) 
Small intestine adenocarcinoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Testicular neoplasm  1  1/3032 (0.03%)  0/3031 (0.00%) 
Transitional cell carcinoma  1  3/3032 (0.10%)  0/3031 (0.00%) 
Nervous system disorders     
Syncope  1  16/3032 (0.53%)  16/3031 (0.53%) 
Presyncope  1  0/3032 (0.00%)  4/3031 (0.13%) 
Carotid artery stenosis  1  6/3032 (0.20%)  3/3031 (0.10%) 
Headache  1  0/3032 (0.00%)  3/3031 (0.10%) 
Hypoaesthesia  1  0/3032 (0.00%)  2/3031 (0.07%) 
Hypoglycaemic unconsciousness  1  3/3032 (0.10%)  2/3031 (0.07%) 
Migraine  1  0/3032 (0.00%)  2/3031 (0.07%) 
Brain injury  1  0/3032 (0.00%)  1/3031 (0.03%) 
Carotid artery dissection  1  0/3032 (0.00%)  1/3031 (0.03%) 
Carotid artery occlusion  1  3/3032 (0.10%)  1/3031 (0.03%) 
Cerebral haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Cervical radiculopathy  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diabetic neuropathy  1  1/3032 (0.03%)  1/3031 (0.03%) 
Dizziness  1  2/3032 (0.07%)  1/3031 (0.03%) 
Facial nerve disorder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Facial paresis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hypoxic-ischaemic encephalopathy  1  0/3032 (0.00%)  1/3031 (0.03%) 
Multiple sclerosis relapse  1  0/3032 (0.00%)  1/3031 (0.03%) 
Optic neuritis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Paraplegia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pyramidal tract syndrome  1  0/3032 (0.00%)  1/3031 (0.03%) 
Radial nerve palsy  1  0/3032 (0.00%)  1/3031 (0.03%) 
Radicular pain  1  0/3032 (0.00%)  1/3031 (0.03%) 
Radiculitis lumbosacral  1  0/3032 (0.00%)  1/3031 (0.03%) 
Transient ischaemic attack  1  1/3032 (0.03%)  1/3031 (0.03%) 
VIIth nerve paralysis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Amyotrophic lateral sclerosis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Aphasia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Carpal tunnel syndrome  1  1/3032 (0.03%)  0/3031 (0.00%) 
Cerebral ischaemia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Cognitive disorder  1  1/3032 (0.03%)  0/3031 (0.00%) 
Convulsion  1  1/3032 (0.03%)  0/3031 (0.00%) 
Depressed level of consciousness  1  1/3032 (0.03%)  0/3031 (0.00%) 
Epilepsy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Essential tremor  1  1/3032 (0.03%)  0/3031 (0.00%) 
Hemiparesis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Intracranial haematoma  1  1/3032 (0.03%)  0/3031 (0.00%) 
Loss of consciousness  1  4/3032 (0.13%)  0/3031 (0.00%) 
Lumbar radiculopathy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Morton's neuralgia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Neuropathy peripheral  1  1/3032 (0.03%)  0/3031 (0.00%) 
Peripheral sensorimotor neuropathy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Psychomotor hyperactivity  1  1/3032 (0.03%)  0/3031 (0.00%) 
Sciatica  1  1/3032 (0.03%)  0/3031 (0.00%) 
Trigeminal neuralgia  1  1/3032 (0.03%)  0/3031 (0.00%) 
VIth nerve paralysis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Psychiatric disorders     
Adjustment disorder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Alcohol abuse  1  0/3032 (0.00%)  1/3031 (0.03%) 
Anxiety  1  1/3032 (0.03%)  1/3031 (0.03%) 
Completed suicide  1  0/3032 (0.00%)  1/3031 (0.03%) 
Confusional state  1  0/3032 (0.00%)  1/3031 (0.03%) 
Depression  1  3/3032 (0.10%)  1/3031 (0.03%) 
Mania  1  0/3032 (0.00%)  1/3031 (0.03%) 
Psychogenic seizure  1  0/3032 (0.00%)  1/3031 (0.03%) 
Suicidal ideation  1  0/3032 (0.00%)  1/3031 (0.03%) 
Conversion disorder  1  1/3032 (0.03%)  0/3031 (0.00%) 
Renal and urinary disorders     
Renal failure acute  1  20/3032 (0.66%)  20/3031 (0.66%) 
Nephrolithiasis  1  8/3032 (0.26%)  7/3031 (0.23%) 
Renal failure  1  5/3032 (0.16%)  6/3031 (0.20%) 
Renal failure chronic  1  4/3032 (0.13%)  6/3031 (0.20%) 
Calculus urinary  1  2/3032 (0.07%)  2/3031 (0.07%) 
Haematuria  1  2/3032 (0.07%)  2/3031 (0.07%) 
Calculus bladder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Calculus ureteric  1  3/3032 (0.10%)  1/3031 (0.03%) 
Hydronephrosis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Nephropathy toxic  1  0/3032 (0.00%)  1/3031 (0.03%) 
Renal artery stenosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Renal colic  1  1/3032 (0.03%)  1/3031 (0.03%) 
Renal impairment  1  2/3032 (0.07%)  1/3031 (0.03%) 
Urethral meatus stenosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Nephropathy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Urinary bladder haemorrhage  1  1/3032 (0.03%)  0/3031 (0.00%) 
Urinary retention  1  1/3032 (0.03%)  0/3031 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  2/3032 (0.07%)  5/3031 (0.16%) 
Prostatitis  1  1/3032 (0.03%)  2/3031 (0.07%) 
Adenomyosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Metrorrhagia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Ovarian cyst ruptured  1  0/3032 (0.00%)  1/3031 (0.03%) 
Prostatism  1  0/3032 (0.00%)  1/3031 (0.03%) 
Prostatomegaly  1  0/3032 (0.00%)  1/3031 (0.03%) 
Vulval ulceration  1  0/3032 (0.00%)  1/3031 (0.03%) 
Ovarian cyst  1  1/3032 (0.03%)  0/3031 (0.00%) 
Uterine prolapse  1  1/3032 (0.03%)  0/3031 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  14/3032 (0.46%)  15/3031 (0.49%) 
Dyspnoea  1  3/3032 (0.10%)  7/3031 (0.23%) 
Acute respiratory failure  1  5/3032 (0.16%)  6/3031 (0.20%) 
Respiratory failure  1  2/3032 (0.07%)  4/3031 (0.13%) 
Asthma  1  4/3032 (0.13%)  3/3031 (0.10%) 
Pleural effusion  1  4/3032 (0.13%)  3/3031 (0.10%) 
Pulmonary embolism  1  8/3032 (0.26%)  3/3031 (0.10%) 
Acute pulmonary oedema  1  1/3032 (0.03%)  2/3031 (0.07%) 
Bronchospasm  1  0/3032 (0.00%)  2/3031 (0.07%) 
Epistaxis  1  0/3032 (0.00%)  2/3031 (0.07%) 
Bronchitis chronic  1  2/3032 (0.07%)  1/3031 (0.03%) 
Cough  1  0/3032 (0.00%)  1/3031 (0.03%) 
Haemothorax  1  1/3032 (0.03%)  1/3031 (0.03%) 
Hydrothorax  1  0/3032 (0.00%)  1/3031 (0.03%) 
Interstitial lung disease  1  1/3032 (0.03%)  1/3031 (0.03%) 
Laryngeal stenosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Lung infiltration  1  0/3032 (0.00%)  1/3031 (0.03%) 
Nasal polyps  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pharyngeal mass  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pneumonia aspiration  1  1/3032 (0.03%)  1/3031 (0.03%) 
Pulmonary hypertension  1  0/3032 (0.00%)  1/3031 (0.03%) 
Respiratory disorder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Respiratory tract haemorrhage  1  1/3032 (0.03%)  1/3031 (0.03%) 
Vocal cord disorder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Wheezing  1  0/3032 (0.00%)  1/3031 (0.03%) 
Acute respiratory distress syndrome  1  1/3032 (0.03%)  0/3031 (0.00%) 
Asthmatic crisis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Dyspnoea exertional  1  1/3032 (0.03%)  0/3031 (0.00%) 
Haemoptysis  1  2/3032 (0.07%)  0/3031 (0.00%) 
Hypoxia  1  1/3032 (0.03%)  0/3031 (0.00%) 
Lung disorder  1  1/3032 (0.03%)  0/3031 (0.00%) 
Obstructive airways disorder  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pickwickian syndrome  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pleurisy  1  2/3032 (0.07%)  0/3031 (0.00%) 
Pulmonary mass  1  1/3032 (0.03%)  0/3031 (0.00%) 
Pulmonary toxicity  1  1/3032 (0.03%)  0/3031 (0.00%) 
Respiratory acidosis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Respiratory distress  1  2/3032 (0.07%)  0/3031 (0.00%) 
Sleep apnoea syndrome  1  2/3032 (0.07%)  0/3031 (0.00%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  4/3032 (0.13%)  8/3031 (0.26%) 
Skin ulcer  1  10/3032 (0.33%)  3/3031 (0.10%) 
Pruritus generalised  1  0/3032 (0.00%)  1/3031 (0.03%) 
Swelling face  1  0/3032 (0.00%)  1/3031 (0.03%) 
Urticaria  1  0/3032 (0.00%)  1/3031 (0.03%) 
Eczema  1  1/3032 (0.03%)  0/3031 (0.00%) 
Hyperhidrosis  1  2/3032 (0.07%)  0/3031 (0.00%) 
Psoriasis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Social circumstances     
Joint prosthesis user  1  0/3032 (0.00%)  1/3031 (0.03%) 
Surgical and medical procedures     
Cardioplegia  1  0/3032 (0.00%)  1/3031 (0.03%) 
Debridement  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hip arthroplasty  1  0/3032 (0.00%)  1/3031 (0.03%) 
Leg amputation  1  0/3032 (0.00%)  1/3031 (0.03%) 
Pleurodesis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Toe amputation  1  1/3032 (0.03%)  1/3031 (0.03%) 
Cholecystectomy  1  1/3032 (0.03%)  0/3031 (0.00%) 
Implantable defibrillator insertion  1  1/3032 (0.03%)  0/3031 (0.00%) 
Intraocular lens implant  1  1/3032 (0.03%)  0/3031 (0.00%) 
Knee arthroplasty  1  1/3032 (0.03%)  0/3031 (0.00%) 
Peripheral artery bypass  1  1/3032 (0.03%)  0/3031 (0.00%) 
Vascular disorders     
Hypertensive crisis  1  13/3032 (0.43%)  15/3031 (0.49%) 
Deep vein thrombosis  1  2/3032 (0.07%)  5/3031 (0.16%) 
Hypertension  1  9/3032 (0.30%)  5/3031 (0.16%) 
Peripheral arterial occlusive disease  1  7/3032 (0.23%)  5/3031 (0.16%) 
Peripheral artery stenosis  1  2/3032 (0.07%)  5/3031 (0.16%) 
Intermittent claudication  1  4/3032 (0.13%)  3/3031 (0.10%) 
Aortic stenosis  1  2/3032 (0.07%)  2/3031 (0.07%) 
Extremity necrosis  1  0/3032 (0.00%)  2/3031 (0.07%) 
Hypotension  1  6/3032 (0.20%)  2/3031 (0.07%) 
Leriche syndrome  1  0/3032 (0.00%)  2/3031 (0.07%) 
Orthostatic hypotension  1  4/3032 (0.13%)  2/3031 (0.07%) 
Peripheral artery aneurysm  1  0/3032 (0.00%)  2/3031 (0.07%) 
Aortic thrombosis  1  0/3032 (0.00%)  1/3031 (0.03%) 
Arterial disorder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Arteritis  1  1/3032 (0.03%)  1/3031 (0.03%) 
Circulatory collapse  1  0/3032 (0.00%)  1/3031 (0.03%) 
Diabetic vascular disorder  1  0/3032 (0.00%)  1/3031 (0.03%) 
Haemorrhage  1  0/3032 (0.00%)  1/3031 (0.03%) 
Hypertensive emergency  1  2/3032 (0.07%)  1/3031 (0.03%) 
Peripheral embolism  1  0/3032 (0.00%)  1/3031 (0.03%) 
Peripheral ischaemia  1  3/3032 (0.10%)  1/3031 (0.03%) 
Peripheral vascular disorder  1  4/3032 (0.13%)  1/3031 (0.03%) 
Shock haemorrhagic  1  0/3032 (0.00%)  1/3031 (0.03%) 
Vascular occlusion  1  0/3032 (0.00%)  1/3031 (0.03%) 
Accelerated hypertension  1  1/3032 (0.03%)  0/3031 (0.00%) 
Aortic dissection  1  1/3032 (0.03%)  0/3031 (0.00%) 
Arterial occlusive disease  1  1/3032 (0.03%)  0/3031 (0.00%) 
Arteriosclerosis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Blood pressure inadequately controlled  1  1/3032 (0.03%)  0/3031 (0.00%) 
Embolism  1  1/3032 (0.03%)  0/3031 (0.00%) 
Essential hypertension  1  2/3032 (0.07%)  0/3031 (0.00%) 
Femoral artery aneurysm  1  1/3032 (0.03%)  0/3031 (0.00%) 
Granulomatosis with polyangiitis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Hypovolaemic shock  1  1/3032 (0.03%)  0/3031 (0.00%) 
Peripheral artery thrombosis  1  2/3032 (0.07%)  0/3031 (0.00%) 
Peripheral venous disease  1  1/3032 (0.03%)  0/3031 (0.00%) 
Vascular stenosis  1  1/3032 (0.03%)  0/3031 (0.00%) 
Vasculitis necrotising  1  1/3032 (0.03%)  0/3031 (0.00%) 
Venous thrombosis limb  1  1/3032 (0.03%)  0/3031 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   1270/3032 (41.89%)   1597/3031 (52.69%) 
Cardiac disorders     
Angina pectoris  1  200/3032 (6.60%)  177/3031 (5.84%) 
Gastrointestinal disorders     
Nausea  1  179/3032 (5.90%)  659/3031 (21.74%) 
Vomiting  1  82/3032 (2.70%)  257/3031 (8.48%) 
Diarrhoea  1  227/3032 (7.49%)  237/3031 (7.82%) 
General disorders     
Non-cardiac chest pain  1  171/3032 (5.64%)  137/3031 (4.52%) 
Infections and infestations     
Nasopharyngitis  1  188/3032 (6.20%)  181/3031 (5.97%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  554/3032 (18.27%)  609/3031 (20.09%) 
Nervous system disorders     
Dizziness  1  191/3032 (6.30%)  259/3031 (8.55%) 
Headache  1  148/3032 (4.88%)  187/3031 (6.17%) 
Vascular disorders     
Hypertension  1  171/3032 (5.64%)  152/3031 (5.01%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trail Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01147250     History of Changes
Other Study ID Numbers: EFC11319
2009-012852-26 ( EudraCT Number )
U1111-1116-5558 ( Other Identifier: UTN )
First Submitted: June 17, 2010
First Posted: June 22, 2010
Results First Submitted: August 22, 2016
Results First Posted: October 14, 2016
Last Update Posted: December 20, 2016