Effect of Nivolumab vs Placebo in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial

Study Overview
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Brief Summary
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Myocardial infarction (MI) is a major contributor to morbidity and mortality in China. The goal of this interventional, randomised controlled clinical trial is to evaluate the effectiveness and safety of a single administration of Nivolumab to the patients presenting with an acute anterior ST-segmental elevated myocardial infarction. Researchers will investigate if Nivolumab treatment can effectively and safely reduce infarct size as well as improve cardiac function of the patients with acute myocardial infarction.

Detailed Description
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The efficacy and safety of nivolumab as compared with placebo in the treatment of acute anterior ST segment elevation myocardial infarction are not known. In this phase 1/2, randomized, placebo-controlled, open-label trial, we randomly assigned adults with acute anterior ST segment elevation myocardial infarction to receive either nivolumab (5mg/kg for single administration) or placebo. The primary end points were difference in infarct size/LV mass% from baseline to 3 months after Nivolumab administration and the incidence of adverse events during 3 months after Nivolumab administration. Secondary end points included difference in LVEF%, LVESV/Body surface area, LVEDV/Body surface area, Trponin T and proBNP from baseline to 3 months after Nivolumab administration.

Official Title
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Effect of Nivolumab vs Placebo in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial

Conditions
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Acute Anterior ST Segment Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Nivolumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 80 years; Signed informed consent and expected compliance with protocol; Acute anterior ST segment elevation myocardial infarction; Emergency coronary angiography for revascularization of occlusive vessels within 24 hours of chest pain onset; Left ventricular ejection fraction is less than 45% (LVEF≤45%) as revealed by Echo within 72 hours after revascularization. Exclusion Criteria: Cardiogenic shock; Cardiac arrest/ventricular fibrillation; History of severe renal failure, glomerular filtration rate (eGFR) < 30ml/min; History of severe infection, hepatobiliary obstruction or malignant tumor; Receiving immunosuppressive therapy; Women who are pregnant or may become pregnant; There are contraindications to study drugs or magnetic resonance examination; No written informed consent was obtained.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional drug treatment group<br>The participants receive Nivolumab treatment. The active drug Nivolumab will be administered at a standard dose (5mg/kg) dissolved in 100ml 0.9%NaCl solution. Nivolumab was given at a rate of 15-25 drops per minute, and the intravenous infusion time exceeded 1 hour. | Drug: Nivolumab<br>* Single administration of Nivolumab on the third day of revascularization after acute anterior ST segment elevation myocardial infarction. The active drug Nivolumab will be administered at a standard dose (5mg/kg) dissolved in 100ml 0.9%NaCl solution. Nivolumab was given at a rate of 15-25 drops per minute, and the intravenous infusion time exceeded 1 hour.<br>|
| Placebo Comparator: Placebo treatment group<br>The participants receive placebo treatment. Patients assigned to the placebo treatment group will receive an intravenous infusion of 100 ml 0.9% NaCl solution at a rate of 15-25 drops/min for an IV infusion duration of more than 1 hour. | Other: Placebo<br>* Single administration of Placebo on the third day of revascularization after acute anterior ST segment elevation myocardial infarction. Patients assigned to the placebo treatment group will receive an intravenous infusion of 100 ml 0.9% NaCl solution at a rate of 15-25 drops/min for an IV infusion duration of more than 1 hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ∆Infarct size/Left Ventricular mass% | Difference in Infarct size/Left ventricular mass% from baseline to 3 months after Nivolumab administration. | 3 months | 
| The incidence of adverse events | The incidence of adverse events during 3 months after Nivolumab treatment. | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ∆Left ventricle ejection fraction% | Difference in Left ventricle ejection fraction% from baseline to 3 months after Nivolumab administration. | 3 months | 
| ∆Left ventricle end systolic volume/Body surface area | Difference in Left ventricle end systolic volume/Body surface area from baseline to 3 months after Nivolumab administration. | 3 months | 
| ∆Left ventricle end diastolic volume/Body surface area | Difference in Left ventricle end diastolic volume/Body surface area from baseline to 3 months after Nivolumab administration. | 3 months | 
| ∆Troponin T | Difference in concentration of Troponin T from baseline to 3 months after Nivolumab administration. | 3 months | 
| ∆proBNP | Difference in concentration of proBNP from baseline to 3 months after Nivolumab administration. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nivolumab, acute anterior ST segment elevation myocardial infarction