Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial

Am Heart J. 2016 Apr:174:103-10. doi: 10.1016/j.ahj.2015.12.009. Epub 2015 Dec 21.

Abstract

Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide-1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years. Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections. The trial will continue until 1,360 confirmed primary composite cardiovascular end points, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, have occurred. The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular end point. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once-weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide once-weekly is noninferior to usual care with respect to the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI is <1.30. EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT01144338.

Publication types

  • Clinical Trial, Phase III
  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Exenatide
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide 1
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Incidence
  • Injections, Subcutaneous
  • Italy / epidemiology
  • Male
  • Microspheres
  • Middle Aged
  • Ontario / epidemiology
  • Peptides / administration & dosage*
  • Prognosis
  • Risk Assessment / methods*
  • Risk Factors
  • Survival Rate / trends
  • Time Factors
  • United Kingdom / epidemiology
  • United States / epidemiology
  • Venoms / administration & dosage*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptide 1
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT01144338