Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial

Abstract

BackgroundMyocardial infarction causes irreversible loss of cardiomyocytes and may lead to loss of ventricular function, morbidity and mortality. Infarct size is a major prognostic factor and reduction of infarct size has therefore been an important objective of strategies to improve outcomes. In experimental studies, glucagon-like peptide 1 and exenatide, a long acting glucagon-like peptide 1 receptor agonist, a novel drug introduced for the treatment of type 2 diabetes, reduced infarct size after myocardial infarction by activating pro-survival pathways and by increasing metabolic efficiency.MethodsThe EXAMI trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate clinical outcome of exenatide infusion on top of standard treatment, in patients with an acute myocardial infarction, successfully treated with primary percutaneous coronary intervention. A total of 108 patients will be randomized to exenatide (5 μg bolus in 30 minutes followed by continuous infusion of 20 μg/24 h for 72 h) or placebo treatment. The primary end point of the study is myocardial infarct size (measured using magnetic resonance imaging with delayed enhancement at 4 months) as a percentage of the area at risk (measured using T2 weighted images at 3-7 days).DiscussionIf the current study demonstrates cardioprotective effects, exenatide may constitute a novel therapeutic option to reduce infarct size and preserve cardiac function in adjunction to reperfusion therapy in patients with acute myocardial infarction.Trial registrationClinicalTrials.gov: NCT01254123

No benefit of additional treatment with exenatide in patients with an acute myocardial infarction

“…The study protocol has been published previously [15]. This multi-centre, prospective, randomized, placebo controlled clinical trial was executed at the VU University Medical Centre, Amsterdam, and the University Medical Centre Utrecht, Utrecht, the Netherlands.…”

“…Magnetic resonance imaging was performed at 3-7 days after ST elevated myocardial infarction and at 4 months of follow-up. The protocol included Cine, T2 weighted (T2W) and late gadolinium enhancement (LGE) imaging [15]. Parameters acquired consisted of left ventricular function (ejection fraction, volumes and left ventricular mass), area at risk using T2W and the endocardial surface area (ESA), microvascular obstruction (MVO) and infarct size at baseline.…”

The use of GLP‐1 receptor agonists in hospitalised patients: An untapped potential

“…The protocol used by the Copenhagen group comprised exenatide or placebo given intravenously 15 minutes prior to intervention and continued 6 hours post‐PCI—at which time blood glucose was 8.0 mmol/L in controls and 6.3 mmol/L with exenatide. Conversely in a study by Roos et al, exenatide was administered for 72 hours after primary angioplasty in 91 individuals, with blood glucose measured every 3 hours on day one, reduced to four‐times per day thereafter; there were no differences in the number of hypoglycaemic episodes (considered <4 mmol/L [10 events in exenatide vs 9 in placebo; 0.530]) or hyperglycaemic episodes (considered >10 mmol/L [3 events in exenatide vs 10 in placebo; 0.064]).…”

Potential Cardiovascular Effects of the Glucagon-like Peptide-1 Receptor Agonists

“…In one trial (NCT01373216), a 72hour infusion of exenatide is being tested for its ability to improve glucose control and cardiac function among patients with type 2 diabetes, coronary atherosclerosis, and LV dysfunction who are undergoing coronary artery bypass grafting; primary outcomes are effects on cardiac function, including cardiac chamber dimensions, LV systolic function, LV diastolic function, and right ventricular systolic function. The Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI) trial (NCT01254123) [101,102] is a pilot study assessing the safety and efficacy of exenatide infusion compared with placebo in patients with an acute MI undergoing pPCI. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial (NCT01144338) is a placebo-controlled phase 4 trial examining exenatide once weekly for improving cardiovascular outcomes in patients with type 2 diabetes.…”