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

Study Overview
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Brief Summary
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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.

Official Title
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Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL). A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Exenatide Once Weekly
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide Once Weekly<br> | Drug: Exenatide Once Weekly<br>* Subcutaneous injection, 2 mg, administered once weekly.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subcutaneous injection, matching volume of placebo, administered once weekly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Outcome MACE Events | 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. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 
| Primary Safety Outcome MACE Events | 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. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Outcome All-Cause Mortality | 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. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 
| Secondary Efficacy Outcome CV Death | Component of the primary efficacy outcome: cardiovascular death. The number of participants who had an event is reported in the results. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 
| Secondary Efficacy Outcome MI | Component of primary efficacy outcome: fatal or non-fatal MI. The number of participants who had an event is reported in the results. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 
| Secondary Efficacy Outcome Stroke | Component of primary efficacy outcome: fatal or non-fatal stroke. The number of participants who had an event is reported in the results. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 
| Secondary Efficacy Outcome Hospitalization for ACS | 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. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 
| Secondary Efficacy Outcome Hospitalization for HF | 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. | Time to first event. Information collected during study period (anticipated to be up to 7.5 years). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exenatide once weekly, cardiovascular, Bydureon, Amylin