A Study of the Safety and Efficacy of Nitric Oxide Reduction in Patients With Cardiogenic Shock After a Heart Attack

Study Overview
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Brief Summary
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Tilarginine Acetate Injection is a new type of drug that temporarily stops the body from making a bodily substance called nitric oxide. The body may produce excess nitric oxide following severe heart damage leading to shock. During a heart attack, and especially after a blocked artery causing the heart attack is reopened, a large amount of nitric oxide is released into the heart muscle and into the blood. Normally small amounts of nitric oxide are good for the heart and blood vessels. However, when released in large amounts, such as during a heart attack, it may be harmful, by adding to the damage of the heart attack and lowering the heart's ability to pump blood to the body. It may cause blood pressure to be lowered and reduce the amount of blood flow to the body's vital organs. This may interfere with the body's organs being able to do their work. If Tilarginine Acetate Injection can stop extra nitric oxide from being made, the performance of the heart and blood flow to the organs may get better, which may result in the improvement of symptoms. The purpose of this study (TRIUMPH) is to investigate the safety and effectiveness of Tilarginine Acetate Injection compared to placebo (an inactive fluid that has no effect on the body but looks exactly like the medication being studied). The study will help determine whether Tilarginine Acetate Injection, by temporarily lowering the amount of nitric oxide released into the vital organs can improve blood pressure and the blood flow to the body's organs.

Detailed Description
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An estimated 120,000 to 160,000 patients annually are diagnosed with cardiogenic shock (CS) in North America and Europe. CS complicates approximately 5-14% of all cases of acute myocardial infarction (AMI) and is the most common cause of death in patients hospitalized with AMI. Cardiogenic shock developing during the course of AMI is the end result of a pathophysiological cycle secondary to a sudden and significant decrease in cardiac contractility due to infarction, ischemia, and stunning of large myocardial segments. It is not anticipated that further advances in reperfusion or revascularization therapy will have a significant additional impact on survival in patients with CS. Modalities that protect the myocardium during ischemia and reperfusion are likely to be the next major advance in improving outcome in the setting of acute myocardial infarction (MI), especially in patients with large infarcts complicated by shock. Preliminary studies investigating nitric oxide synthase (NOS) inhibition suggest that improvements in cardiovascular function and survival are possible by limiting formation of toxic NO. The primary objective of the TRIUMPH study is to establish the efficacy of Tilarginine Acetate Injection compared to placebo in reducing all cause mortality at 30 days post randomization in patients with cardiogenic shock complicating acute myocardial infarction (MI). Safety objectives of this study include an evaluation of adverse events and serious adverse events, and key laboratory parameters.

Official Title
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A Phase III International, Multi-Center, Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Nitric Oxide Synthase Inhibition With Tilarginine Acetate Injection in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction, or the TRIUMPH Trial

Conditions
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Shock, Cardiogenic

Intervention / Treatment
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* Drug: Tilarginine Acetate Injection intravenous infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed myocardial infarction (heart attack) Confirmed persistent cardiogenic shock Confirmed patency of the infarct related artery (heart attack artery has been opened through the use of a blood clot dissolving drug or a balloon or angioplasty heart procedure) Less than 24 hour duration of cardiogenic shock (the time since the heart attack occurred and the artery was opened must be less than 24 hours) Exclusion Criteria: Infection Other cause of shock (not heart attack) Shock due to heart valve disease Severe heart valve disease Right sided heart failure Shock due to arrhythmia (irregular heart rhythm) Severe kidney disease Aortic dissection (tear in aorta) Adult respiratory distress syndrome (ARDS) (severe lung inflammation) Severe brain damage Severe irreversible multi-system failure (failure of multiple body organs) Major chest or abdominal surgical procedure within 30 days except if prior CABG and reocclusion occurs Primary pulmonary hypertension (high blood pressure in the arteries of the lungs) Age younger than 18 years Requirement for emergency coronary artery bypass grafting (CABG) or infarct-related artery occlusion (heart attack artery completely blocked) Ongoing or recent participation in another clinical trial of an investigational drug Prior enrollment in this study or rapid resolution of cardiogenic shock before treatment (shock gets better before study starts) Positive pregnancy test in women who are of childbearing potential

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tilarginine Acetate Injection intravenous infusion|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality at 30 days post randomization |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients demonstrating resolution of cardiogenic shock compared to placebo |  |  | 
| The duration of cardiogenic shock compared to placebo |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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shock, cardiogenic, myocardial infarction