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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00112281
Recruitment Status : Terminated
First Posted : June 2, 2005
Last Update Posted : August 4, 2006
Information provided by:
Arginox Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE June 1, 2005
First Posted Date  ICMJE June 2, 2005
Last Update Posted Date August 4, 2006
Study Start Date  ICMJE May 2005
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2005)
All cause mortality at 30 days post randomization
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Study of the Safety and Efficacy of Nitric Oxide Reduction in Patients With Cardiogenic Shock After a Heart Attack
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Shock, Cardiogenic
Intervention  ICMJE Drug: Tilarginine Acetate Injection intravenous infusion
Study Arms  ICMJE 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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Enrollment  ICMJE
 (submitted: May 10, 2006)
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
Study Completion Date  ICMJE January 2007
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00112281
Other Study ID Numbers  ICMJE ARG-CS3-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Not Provided
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Arginox Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Judith S. Hochman, M.D. NYU Langone Health
PRS Account Arginox Pharmaceuticals
Verification Date May 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP