Myocardial Injury After Noncardiac Surgery (MINS) Clinical Trial
Official title:
A Large, International, Randomized, Placebo-controlled Trial to Assess the Impact of Dabigatran (a Direct Thrombin Inhibitor) and Omeprazole (a Proton-pump Inhibitor) in Patients Suffering Myocardial Injury After Noncardiac Surgery
Patients who have myocardial injury after noncardiac surgery are at a higher risk of dying than those who do not. One in 10 patients with myocardial injury will die within 30 days of surgery. This risk of death exists up to one year after myocardial injury. There are currently no treatments or guidelines available for heart injury after surgery, but there is evidence that taking a blood-thinner can prevent some of the deaths, both in the short and long-term. The purpose of this trial is to test the effect of two drugs (dabigatran and omeprazole) that may prevent mortality, major cardiovascular complications and major upper gastrointestinal bleeding in patients who have had myocardial injury after noncardiac surgery.
Myocardial injury is the most common major vascular complication after noncardiac surgery.
Worldwide approximately 10 million adults annually suffer a perioperative myocardial injury.
This figure for perioperative myocardial injury represents 15-20% of all cases of myocardial
infarction in all settings. Myocardial injury after noncardiac surgery carries a poor
prognosis and is an independent predictor of 30-day and 1-year mortality.
Myocardial injury after noncardiac surgery (MINS) differs from non-operative myocardial
infarction in two ways; it has a poorer prognosis (patients suffering MINS are 2 times more
likely to die within 30 days compared to non-operative myocardial infarction in the emergency
room) and paradoxically its treatment is less intensive. This difference in the intensity of
treatment is likely influenced by several factors including: (1) a majority of patients
suffering MINS do not experience ischemic symptoms, potentially influencing physicians'
perception of the severity of the event; (2) there is debate as to the pathophysiology of
MINS (although emerging evidence does suggest that coronary arterial thrombosis is an
important mechanism of MINS); and (3) no randomized controlled trial (RCT) has evaluated an
intervention to manage MINS, and hence physicians are uncertain about the risk-benefit ratio
of potential interventions (e.g., interventions that are effective in the management of
non-operative myocardial infarction). From a human and economic perspective, it is a tragedy
that some patients undergoing noncardiac surgery for important reasons (e.g., to obtain a
cure of their cancer or to become mobile after a new prosthetic joint) fail to obtain these
benefits, because they suffer MINS that ultimately takes their life. There is an urgent need
for clinical trials to identify effective therapies to improve the outcomes of patients
suffering MINS.
There exists promising laboratory, autopsy, imaging, operative, and non-operative data
suggesting that patients suffering MINS will benefit from anticoagulant therapy. Dabigatran
(a direct thrombin inhibitor) warrants evaluation in the management of MINS. The major
limitation of anticoagulation therapy is bleeding, and gastrointestinal bleeding represents a
substantial proportion of these complications. Gastrointestinal bleeding is important in its
own right, but also because it leads to cessation of anticoagulant therapy which may lead to
breakthrough myocardial infarction. Omeprazole (a proton pump inhibitor) is efficacious in
preventing upper gastrointestinal bleeding in patients with coronary artery disease who are
taking dual antiplatelet therapy, and may benefit patients receiving anticoagulation therapy
after suffering MINS.
We will undertake a large international RCT to determine the impact of dabigatran in patients
who have suffered MINS. We will use a partial factorial design (for patients not taking a
proton pump inhibitor) to determine the impact of omeprazole in this setting. We call this
RCT the Management of myocardial injury After NoncArdiac surGEry (MANAGE) Trial.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05279651 -
Ivabradine for Prevention of Myocardial Injury After Noncardiac Surgery Trial (PREVENT-MINS)
|
Phase 3 |