Dabigatran for the Prevention of Myocardial Injury after Orthopedic Surgery (DMINS-PRE). A Study Protocol For A Randomized, Active-Controlled, Phase II Trial

Abstract

Background and Aims: Myocardial Injury after Noncardiac Surgery (MINS) is a broader term that includes not only perioperative myocardial infarction but also other prognostically significant myocardial injuries due to ischemia, within 30 days after noncardiac surgery. Annually, around 1 million patients who undergo noncardiac surgery worldwide die during the first 30 days following surgery. The incidence of MINS is around 5-8%, with the majority occurring in the first two days after surgery. A recent study showed a potential positive effect of Dabigatran to prevent major vascular complications among patients with MINS. However, until now there is no evidence related to whether any effective drug may reduce its incidence. Our study aims to assess the efficacy of dabigatran to prevent MINS in a high cardiovascular risk population.
Methods: This study will be a multicenter randomized, two-arms (1:1 ratio), active-controlled and double-dummy, phase II trial. We will study 264 adults (45-75 years) with a high cardiovascular risk, assessed by the Framingham Risk Score, who are undergoing elective orthopedic surgery. Patients which troponin measurement keeps negative after surgery will be randomly assigned (1:1) to receive dabigatran 150mg twice daily or enoxaparin daily, 6 hours after surgery for seven days. The primary outcome will be the incidence of MINS as ascertained by the difference in troponin (troponin delta) greater than 14ng/L in the perioperative period, after randomization. Secondary outcomes will be 30-day mortality, major thromboembolic complications, and severe bleeding complications.
The potential impact of the study: This clinical trial will be the first to assess the efficacy and the safety of dabigatran to prevent MINS. Given MINS is estimated to affect every year about 8 million patients worldwide and is associated with cardiovascular complications and death after surgery, we believe this trial will provide relevant data to clinical practice and future research directions.