Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Placebo
Drug: Exenatide Once Weekly

Registration Number: NCT01144338

Lead Sponsor: AstraZeneca

Brief Summary: This study will compare the impact of including exenatide once weekly in addition to usual care vs. usual care without exenatide on major cardiovascular outcomes as measured by the primary composite endpoint of cardiovascular-related death, nonfatal myocardial infarction (MI), or nonfatal stroke.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14752

Inclusion Criteria

Patient has type 2 diabetes mellitus
Patient has an HbA1c of ≥ 6.5 % and ≤ 10.0% and is currently using one of the following treatment regimens: A) Treatment with 0-3 oral antihyperglycemic agents B) Insulin therapy, either alone or in combination with up to two oral agents
Female patients must not be breast feeding and agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant.

Exclusion Criteria

Patient has a diagnosis of type 1 diabetes mellitus, or a history of ketoacidosis.
Patient has ever been treated with an approved or investigational GLP-1 receptor agonist.
Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial.
Patient has a planned or anticipated revascularization procedure.
Pregnancy or planned pregnancy during the trial period.
Patient has end-stage renal disease or an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m2.
Patient has a history of gastroparesis or pancreatitis.
Personal or family history of medullary thyroid cancer or MEN2 (Multiple EndocrineNeoplasia Type 2) or calcitonin level of >40 ng/L at baseline.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Exenatide Once Weekly	Exenatide Once Weekly	-

Primary Outcome Measures

Name	Time	Method
Primary Efficacy Outcome MACE Events	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	The primary efficacy outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. The number of participants who had an event is reported in the results. The primary efficacy endpoint is the same as the primary safety endpoint, and the statistical analysis tests the superiority of exenatide against the placebo.
Primary Safety Outcome MACE Events	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	The primary safety outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. The number of participants who had an event is reported in the results. The primary safety endpoint is the same as the primary efficacy endpoints, and the statistical analysis tests the non-inferiority of exenatide against placebo.

Secondary Outcome Measures

Name	Time	Method
Secondary Efficacy Outcome All-Cause Mortality	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	The secondary efficacy outcome variable is defined as the all-cause mortality (deaths). The number of participants who had an event is reported in the results.
Secondary Efficacy Outcome CV Death	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	Component of the primary efficacy outcome: cardiovascular death. The number of participants who had an event is reported in the results.
Secondary Efficacy Outcome Hospitalization for HF	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	The secondary efficacy outcome variable is defined as hospitalization for heart failure. The number of participants who had an event is reported in the results.
Secondary Efficacy Outcome MI	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	Component of primary efficacy outcome: fatal or non-fatal MI. The number of participants who had an event is reported in the results.
Secondary Efficacy Outcome Stroke	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	Component of primary efficacy outcome: fatal or non-fatal stroke. The number of participants who had an event is reported in the results.
Secondary Efficacy Outcome Hospitalization for ACS	Time to first event. Information collected during study period (anticipated to be up to 7.5 years).	The secondary efficacy outcome variable is defined as hospitalization for acute coronary syndrome. The number of participants who had an event is reported in the results.