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

This study has been terminated.
Sponsor:
Information provided by:
Arginox Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00112281
First received: June 1, 2005
Last updated: August 2, 2006
Last verified: May 2005
  Purpose

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.


Condition Intervention Phase
Shock, Cardiogenic
Drug: Tilarginine Acetate Injection intravenous infusion
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Arginox Pharmaceuticals:

Primary Outcome Measures:
  • All cause mortality at 30 days post randomization

Secondary Outcome Measures:
  • Number of patients demonstrating resolution of cardiogenic shock compared to placebo
  • The duration of cardiogenic shock compared to placebo

Estimated Enrollment: 658
Study Start Date: May 2005
Estimated Study Completion Date: January 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112281

  Hide Study Locations
Locations
United States, Alabama
The Heart Group, PC
Mobile, Alabama, United States, 36608
United States, Arizona
Sparks Regional Medical Center
Fort Smith, Arizona, United States, 72901
Banner Baywood Heart Hospital
Mesa, Arizona, United States, 85206
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85043
United States, Arkansas
Central Arkansas Cardiovascular Research Group (CACRG)
Little Rock, Arkansas, United States, 72205
United States, California
Los Angeles Cardiology Associates
Los Angeles, California, United States, 90017
University of Southern California, LAC + USC Medical Center
Los Angeles, California, United States, 90033
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Stanford University School of Medicine
Palo Alto, California, United States, 94305-5406
Desert Cardiology
Rancho Mirage, California, United States, 92270
Mercy General Hospital
Sacramento, California, United States, 95819
United States, Colorado
South Denver Cardiology Associates, PC
Littleton, Colorado, United States, 80120
United States, Delaware
Christiana Care Health Services
Newark, Delaware, United States, 19718
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010-2975
United States, Florida
Florida Cardiovascular Research Center
Atlantis, Florida, United States, 33462
Watson Clinic, LLP
Lakeland, Florida, United States, 33805
Health First Clinical Research Institute
Melbourne, Florida, United States, 32901
University of Miami School of Medicine
Miami, Florida, United States, 33136
Mt. Sinai Medical Center
Miami, Florida, United States, 33140
Mediquest Research Group
Ocala, Florida, United States, 34471
Orlando Regional Medical Center
Orlando, Florida, United States, 32806
Cardiovascular Center of Sarasota
Sarasota, Florida, United States, 34239
United States, Georgia
Emory Crawford Long Hospital
Atlanta, Georgia, United States, 30308
United States, Illinois
John H. Stroger Jr. Hospital of Cook County
Chicago, Illinois, United States, 60612
Heart Care Midwest
Peoria, Illinois, United States, 61603
Trinity Medical Center
Rock Island, Illinois, United States, 61201
United States, Indiana
Parkview Research Center
Fort Wayne, Indiana, United States, 46805
United States, Iowa
Iowa Health, Des Moines
Des Moines, Iowa, United States, 50309
Iowa Heart Centre
Des Moines, Iowa, United States, 50314
University of Iowa Hospital
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Hospital
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536-0200
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maine
Northeast Cardiology Associates
Bangor, Maine, United States, 04401
Maine Medical Center
Portland, Maine, United States, 04102
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Boston Medical Center
Boston, Massachusetts, United States, 02118
Interventional Cardiovascular Research - Lahey Clinic
Burlington, Massachusetts, United States, 01805
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
Fallon Cardiology - St. Vincent Hospital
Worchester, Massachusetts, United States, 01608
United States, Michigan
University of Michigan Health Systems
Ann Arbor, Michigan, United States, 48109-0311
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Spectrum Health Hospitals
Grand Rapids, Michigan, United States, 49525
Nisus Research at Northern Michigan Hospital
Petoskey, Michigan, United States, 49770
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073-6769
United States, Minnesota
St. Mary's Duluth Clinic Health System
Duluth, Minnesota, United States, 55805
Mayo Clinic Minnesota
Rochester, Minnesota, United States, 55905
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63110
Washington University
St. Louis, Missouri, United States, 63110
United States, Nebraska
BryanLGH Heart Institute
Lincoln, Nebraska, United States, 68516
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-2265
United States, New Jersey
Cooper Health System
Camden, New Jersey, United States, 08103
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
United States, New York
Lenox Hill Heart and Vascular Institute of New York
New York, New York, United States, 10021
Mount Sinai Medical Center
New York, New York, United States, 10029
Rochester Cardio-Pulmonary Group, P.C.
Rochester, New York, United States, 14621
University of Rochester Medical Center
Rochester, New York, United States, 14642
Cardiology Associates of Schenectady
Schenectady, New York, United States, 12309
United States, North Carolina
Mission Hospitals
Asheville, North Carolina, United States, 28801
UNC Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7075
Sanger Clinic
Charlotte, North Carolina, United States, 28203
Duke University Medical Center
Durham, North Carolina, United States, 27710
LeBauer Cardiovascular Research
Greensboro, North Carolina, United States, 27401
Forsyth Medical Center
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
MidWest Cardiology Research Foundation
Columbus, Ohio, United States, 43214
United States, Oregon
The Oregon Clinic
Portland, Oregon, United States, 97213-2281
Providence Heart & Vascular Institute
Portland, Oregon, United States, 97225
United States, Pennsylvania
The Heart Care Group
Allentown, Pennsylvania, United States, 18106
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Lancaster General Hospital
Lancaster, Pennsylvania, United States, 17603
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
Guthrie Clinic
Sayre, Pennsylvania, United States, 18830
United States, Rhode Island
The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, South Carolina
South Carolina Heart Center
Columbia, South Carolina, United States, 29204
United States, Tennessee
Johnson City Medical Center
Johnson City, Tennessee, United States, 37601
St. Thomas Cardiology Consultants
Nashville, Tennessee, United States, 37205
United States, Texas
Ben Taub General Hospital, Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Medical School
Houston, Texas, United States, 77030
The Methodist Hospital
Houston, Texas, United States, 77030
United States, Utah
LDS Hospital
Salt Lake City, Utah, United States, 84143
United States, Vermont
Fletcher Allen Healthcare
Burlington, Vermont, United States, 05401
Canada, Alberta
Calgary Heart Centre Alberta
Calgary, Alberta, Canada, T2N 2T9
Royal Alexandria Hospital
Edmonton, Alberta, Canada, T5H3V9
University of Alberta
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Vancouver Hospital and Health Sciences Centre
Vancouver, British Columbia, Canada, V5Z 1L8
Victoria Heart Institute Foundation
Victoria, British Columbia, Canada, V8R 4R2
Canada, Manitoba
St. Boniface General Hospital
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, New Brunswick
NB Heart Centre
St. John, New Brunswick, Canada, E2L 4L2
Canada, Nova Scotia
QEII Health Science Centre - Cardiology Research
Halifax, Nova Scotia, Canada, B3H 3A7
Cardiology Research - QEII Health Science Centre
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Hamilton Health Sciences, General Site
Hamilton, Ontario, Canada, L8L 2X2
London Health Sciences Centre
London, Ontario, Canada, N6A 4G5
Trilium Health Centre
Mississauga, Ontario, Canada, L5B 2P7
Southlake Regional Health Centre
Newmarket, Ontario, Canada, L3Y 2R2
University of Ottawa
Ottawa, Ontario, Canada, K1Y 4W7
University Health Network - Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
St. Michael's Hospital Toronto
Toronto, Ontario, Canada, M5B 1W8
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
Canada
Quebec Heart Institute
Quebec, Canada, G1V 4G5
Sponsors and Collaborators
Arginox Pharmaceuticals
Investigators
Study Chair: Judith S. Hochman, M.D. New York University School of Medicine
  More Information

No publications provided by Arginox Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00112281     History of Changes
Other Study ID Numbers: ARG-CS3-001
Study First Received: June 1, 2005
Last Updated: August 2, 2006
Health Authority: United States: Food and Drug Administration

Keywords provided by Arginox Pharmaceuticals:
shock, cardiogenic, "myocardial infarction"

Additional relevant MeSH terms:
Myocardial Infarction
Shock
Shock, Cardiogenic
Cardiovascular Diseases
Heart Diseases
Myocardial Ischemia
Pathologic Processes
Vascular Diseases
Nitric Oxide
Omega-N-Methylarginine
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Enzyme Inhibitors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014