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

Tracking Information
First Submitted Date ICMJE	June 17, 2010
First Posted Date ICMJE	June 22, 2010
Results First Submitted Date	August 22, 2016
Results First Posted Date	October 14, 2016
Last Update Posted Date	December 20, 2016
Study Start Date ICMJE	June 2010
Actual Primary Completion Date	February 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 22, 2016)	Time to First Occurence of Primary CV Event: CV Death, Non-Fatal MI, Non-Fatal Stroke or Hospitalization for Unstable Angina [ Time Frame: From randomization up to the end of study (median follow-up of 25 months) ]; 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.
Original Primary Outcome Measures ICMJE; (submitted: June 17, 2010)	Time to the first occurrence of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, adjudicated and validated by the Cardiovascular Events Adjudication Committee (CAC) [ Time Frame: week 0 to week 176 ]
Change History	Complete list of historical versions of study NCT01147250 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 31, 2016)	Time to First Occurence of CV Event: CV Death, Non-Fatal MI, Non-Fatal Stroke, Hospitalization for Unstable Angina or Hospitalization For Heart Failure [ Time Frame: From randomization up to the end of study (median follow-up of 25 months) ]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 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 [ Time Frame: From randomization up to the end of study (median follow-up of 25 months) ]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.; Percent Change From Baseline in the Urinary Albumin/Creatinine Ratio (UACR) at Week 108 [ Time Frame: Baseline to Week 108 (LOCF) ]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.
Original Secondary Outcome Measures ICMJE; (submitted: June 17, 2010)	Time to the first occurrence of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure adjudicated and validated by the CAC [ Time Frame: week 0 to week 176 ]; Time to the first occurrence of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, hospitalization for coronary revascularization procedure adjudicated and validated by the CAC [ Time Frame: week 0 to week 176 ]; Percent change in the urinary albumin/creatinine ratio [ Time Frame: from baseline to 108 weeks ]; Glycosylated haemoglobin HbA1c [ Time Frame: week 0 to week 176 ]; Fasting plasma glucose (FPG) [ Time Frame: week 0 to week 176 ]; body weight change [ Time Frame: week 0 to week 176 ]; Cardiovascular risk markers: high-sensitivity C-reactive protein (hs-CRP), brain natriuretic peptide (BNP), N-terminal prohormone brain natriuretic peptide (NT-proBNPs) [ Time Frame: week 0 to week 176 ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With AVE0010 (Lixisenatide)
Official Title ICMJE	A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate Cardiovascular Outcomes During Treatment With Lixisenatide in Type 2 Diabetic Patients After an Acute Coronary Syndrome
Brief Summary	Primary Objective: - To demonstrate that lixisenatide can reduce cardiovascular (CV) morbidity and mortality (composite endpoint of CV death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina) compared to placebo in type 2 diabetic participants who recently experienced an acute coronary syndrome (ACS) event. Secondary Objectives: To demonstrate that when compared to placebo, lixisenatide can reduce: composite endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, or hospitalization for heart failure.; composite endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization procedure.; urinary albumin excretion (based on the urinary albumin/creatinine ratio). To assess the safety and tolerability of lixisenatide.
Detailed Description	The estimated maximum study duration for the first randomized participant was approximately 204 weeks (± 14 days), with a median follow-up over all participants of approximately 91 weeks, broken down as follows: placebo-run-in period: 7 days (+ 3 days); double-blind study treatment period: 203 weeks (± 14 days) (with about a 37 months of recruitment period); post-treatment follow-up period: 3 days (± 1 day) All participants were followed from randomization until the end of study, which should occur when the last randomized participant had been followed for approximately 10 months. The actual end date of the study was "event driven" and the study end when there were approximately 844 positively-adjudicated primary cardiovascular outcome events.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Acute Coronary Syndrome
Intervention ICMJE	Drug: Lixisenatide (AVE0010) Pharmaceutical form: Sterile aqueous solution; Route of administration: Subcutaneous within 1-hour before breakfast using self-injector pen device (Opticlik®). If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 15 or 10 mcg. Other Name: Lyxumia; Drug: Placebo Pharmaceutical form: Sterile aqueous solution; Route of administration: Subcutaneous within 1-hour before breakfast.
Study Arms	Placebo Comparator: Placebo Placebo matched to lixisenatide once daily (QD) up to end of treatment. Intervention: Drug: Placebo; Experimental: Lixisenatide Lixisenatide 10 mcg QD for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment. Intervention: Drug: Lixisenatide (AVE0010)
Publications *	Bentley-Lewis R, Aguilar D, Riddle MC, Claggett B, Diaz R, Dickstein K, Gerstein HC, Johnston P, Køber LV, Lawson F, Lewis EF, Maggioni AP, McMurray JJ, Ping L, Probstfield JL, Solomon SD, Tardif JC, Wu Y, Pfeffer MA; ELIXA Investigators. Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo. Am Heart J. 2015 May;169(5):631-638.e7. doi: 10.1016/j.ahj.2015.02.002. Epub 2015 Feb 12.; Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, Lawson FC, Ping L, Wei X, Lewis EF, Maggioni AP, McMurray JJ, Probstfield JL, Riddle MC, Solomon SD, Tardif JC; ELIXA Investigators. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015 Dec 3;373(23):2247-57. doi: 10.1056/NEJMoa1509225.; Wolsk E, Claggett B, Pfeffer MA, Diaz R, Dickstein K, Gerstein HC, Lawson FC, Lewis EF, Maggioni AP, McMurray JJV, Probstfield JL, Riddle MC, Solomon SD, Tardif JC, Køber L. Role of B-Type Natriuretic Peptide and N-Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus. J Am Heart Assoc. 2017 May 29;6(6). pii: e004743. doi: 10.1161/JAHA.116.004743.; Wohlfart P, Linz W, Hübschle T, Linz D, Huber J, Hess S, Crowther D, Werner U, Ruetten H. Cardioprotective effects of lixisenatide in rat myocardial ischemia-reperfusion injury studies. J Transl Med. 2013 Mar 28;11:84. doi: 10.1186/1479-5876-11-84.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: August 22, 2016)	6068
Original Estimated Enrollment ICMJE; (submitted: June 17, 2010)	6000
Actual Study Completion Date	February 2015
Actual Primary Completion Date	February 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion criteria: Men and women who experienced a spontaneous ACS event (i.e., ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation MI (NSTEMI) or unstable angina) with a documented elevation above the normal reference range of a cardiac biomarker (Troponin or Creatinine Kinase (CK)-MB) and the clinical presentation consistent with an ACS which lead to admission to an acute care facility, within 180 days following the ACS event and prior to screening.; Participants with a history of type 2 diabetes (for participants newly diagnosed, diagnosis was based on the World Health Organization (WHO) criteria: i.e., either a fasting venous plasma glucose concentration ≥ 7.0 mmol/L [126 mg/dL] or 2-hour post glucose load venous plasma glucose ≥ 11.1 mmol/L [200 mg/dL], confirmed on 2 occasions) prior to the screening visit. Exclusion criteria: Type 1 diabetes mellitus or history of ketoacidosis within 6 months prior to screening.; Glycosylated hemoglobin (HbA1c) <5.5 % or >11% measured at screening visit.; Required to use incretin-based agents (e.g., Glucagon-like peptide -1 (GLP-1) agonists or Dipeptidyl Peptidase-4 (DPP-4) inhibitors) other than the study drug during the double-blind treatment period.; Participants who had undergone coronary artery bypass graft (CABG) surgery following the qualifying ACS event.; Participants who had undergone percutaneous coronary intervention (PCI) within 15 days prior to screening.; Participants with planned revascularization procedure (PCI or CABG) or coronary angiogram within 90 days after screening visit.; History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC), or genetic conditions that predisposes to MTC (e.g., multiple endocrine neoplasia syndromes).; Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Sex/Gender	Sexes Eligible for Study: All
Ages	30 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Denmark, Ecuador, Egypt, Estonia, Finland, France, Georgia, Germany, Guatemala, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Norway, Panama, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Sweden, Switzerland, Taiwan, Tunisia, Turkey, Ukraine, United Arab Emirates, United Kingdom, United States
Removed Location Countries	Puerto Rico
Administrative Information
NCT Number ICMJE	NCT01147250
Other Study ID Numbers ICMJE	EFC11319; 2009-012852-26 ( EudraCT Number ); U1111-1116-5558 ( Other Identifier: UTN )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sanofi
Study Sponsor ICMJE	Sanofi
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Clinical Sciences & Operations Sanofi
PRS Account	Sanofi
Verification Date	October 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP