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

NCT ID: NCT00112281

Last Updated: 2006-08-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 658 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2007-01-31

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.

Conditions

Shock, Cardiogenic

Keywords

shock, cardiogenic, "myocardial infarction"

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Tilarginine Acetate Injection intravenous infusion

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arginox Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Principal Investigators

Judith S. Hochman, M.D.

Role: STUDY_CHAIR

NYU Langone Health

Locations

The Heart Group, PC

Mobile, Alabama, United States

Sparks Regional Medical Center

Fort Smith, Arizona, United States

Banner Baywood Heart Hospital

Mesa, Arizona, United States

Mayo Clinic Hospital

Phoenix, Arizona, United States

Central Arkansas Cardiovascular Research Group (CACRG)

Little Rock, Arkansas, United States

Los Angeles Cardiology Associates

Los Angeles, California, United States

University of Southern California, LAC + USC Medical Center

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Stanford University School of Medicine

Palo Alto, California, United States

Desert Cardiology

Rancho Mirage, California, United States

Mercy General Hospital

Sacramento, California, United States

South Denver Cardiology Associates, PC

Littleton, Colorado, United States

Christiana Care Health Services

Newark, Delaware, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Florida Cardiovascular Research Center

Atlantis, Florida, United States

Watson Clinic, LLP

Lakeland, Florida, United States

Health First Clinical Research Institute

Melbourne, Florida, United States

University of Miami School of Medicine

Miami, Florida, United States

Mt. Sinai Medical Center

Miami, Florida, United States

Mediquest Research Group

Ocala, Florida, United States

Orlando Regional Medical Center

Orlando, Florida, United States

Cardiovascular Center of Sarasota

Sarasota, Florida, United States

Emory Crawford Long Hospital

Atlanta, Georgia, United States

John H. Stroger Jr. Hospital of Cook County

Chicago, Illinois, United States

Heart Care Midwest

Peoria, Illinois, United States

Trinity Medical Center

Rock Island, Illinois, United States

Parkview Research Center

Fort Wayne, Indiana, United States

Iowa Health, Des Moines

Des Moines, Iowa, United States

Iowa Heart Centre

Des Moines, Iowa, United States

University of Iowa Hospital

Iowa City, Iowa, United States

University of Kansas Hospital

Kansas City, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Northeast Cardiology Associates

Bangor, Maine, United States

Maine Medical Center

Portland, Maine, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Interventional Cardiovascular Research - Lahey Clinic

Burlington, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Fallon Cardiology - St. Vincent Hospital

Worchester, Massachusetts, United States

University of Michigan Health Systems

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Spectrum Health Hospitals

Grand Rapids, Michigan, United States

Nisus Research at Northern Michigan Hospital

Petoskey, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

St. Mary's Duluth Clinic Health System

Duluth, Minnesota, United States

Mayo Clinic Minnesota

Rochester, Minnesota, United States

Saint Louis University

St Louis, Missouri, United States

Washington University

St Louis, Missouri, United States

BryanLGH Heart Institute

Lincoln, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Cooper Health System

Camden, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Lenox Hill Heart and Vascular Institute of New York

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Rochester Cardio-Pulmonary Group, P.C.

Rochester, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Cardiology Associates of Schenectady

Schenectady, New York, United States

Mission Hospitals

Asheville, North Carolina, United States

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Sanger Clinic

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

LeBauer Cardiovascular Research

Greensboro, North Carolina, United States

Forsyth Medical Center

Winston-Salem, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

MidWest Cardiology Research Foundation

Columbus, Ohio, United States

The Oregon Clinic

Portland, Oregon, United States

Providence Heart & Vascular Institute

Portland, Oregon, United States

The Heart Care Group

Allentown, Pennsylvania, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Guthrie Clinic

Sayre, Pennsylvania, United States

The Miriam Hospital

Providence, Rhode Island, United States

South Carolina Heart Center

Columbia, South Carolina, United States

Johnson City Medical Center

Johnson City, Tennessee, United States

St. Thomas Cardiology Consultants

Nashville, Tennessee, United States

Ben Taub General Hospital, Baylor College of Medicine

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

University of Texas Medical School

Houston, Texas, United States

LDS Hospital

Salt Lake City, Utah, United States

Fletcher Allen Healthcare

Burlington, Vermont, United States

Calgary Heart Centre Alberta

Calgary, Alberta, Canada

Royal Alexandria Hospital

Edmonton, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Vancouver Hospital and Health Sciences Centre

Vancouver, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Victoria Heart Institute Foundation

Victoria, British Columbia, Canada

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

NB Heart Centre

Saint John, New Brunswick, Canada

Cardiology Research - QEII Health Science Centre

Halifax, Nova Scotia, Canada

QEII Health Science Centre - Cardiology Research

Halifax, Nova Scotia, Canada

Hamilton Health Sciences, General Site

Hamilton, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Trilium Health Centre

Mississauga, Ontario, Canada

Southlake Regional Health Centre

Newmarket, Ontario, Canada

University of Ottawa

Ottawa, Ontario, Canada

St. Michael's Hospital Toronto

Toronto, Ontario, Canada

University Health Network - Toronto General Hospital

Toronto, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Quebec Heart Institute

Québec, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 17387132 (View on PubMed)

Other Identifiers

ARG-CS3-001

Identifier Type: -

Identifier Source: org_study_id