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

• ClinicalTrials.gov Identifier: NCT00112281
• Recruitment Status: Terminated
• First Posted: June 2, 2005
• Last Update Posted: August 4, 2006
• Sponsor: Arginox Pharmaceuticals
• Information provided by: Arginox Pharmaceuticals

Tracking Information

• First Submitted Date: June 1, 2005
• First Posted Date: June 2, 2005
• Last Update Posted Date: August 4, 2006
• Study Start Date: May 2005
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: June 23, 2005): All cause mortality at 30 days post randomization
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 23, 2005)

• Number of patients demonstrating resolution of cardiogenic shock compared to placebo
• The duration of cardiogenic shock compared to placebo

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Safety and Efficacy of Nitric Oxide Reduction in Patients With Cardiogenic Shock After a Heart Attack
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Shock, Cardiogenic
• Intervention: Drug: Tilarginine Acetate Injection intravenous infusion
• Study Arms: Not Provided
• Publications *: TRIUMPH Investigators; Alexander JH, Reynolds HR, Stebbins AL, Dzavik V, Harrington RA, Van de Werf F, Hochman JS. Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. JAMA. 2007 Apr 18;297(15):1657-66. doi: 10.1001/jama.297.15.joc70035. Epub 2007 Mar 26.

Recruitment Information

• Recruitment Status: Terminated
• Enrollment (submitted: May 10, 2006): 658
• Original Enrollment (submitted: June 23, 2005): 650
• Study Completion Date: January 2007
• Primary Completion Date: Not Provided

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00112281
• Other Study ID Numbers: ARG-CS3-001
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Arginox Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Judith S. Hochman, M.D.; NYU Langone Health

• PRS Account: Arginox Pharmaceuticals
• Verification Date: May 2005