A Study of the Safety and Efficacy of Nitric Oxide Reduction in Patients With Cardiogenic Shock After a Heart Attack
- Conditions
- Shock, Cardiogenic
- Registration Number
- NCT00112281
- Lead Sponsor
- Arginox Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 658
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method All cause mortality at 30 days post randomization
- Secondary Outcome Measures
Name Time Method Number of patients demonstrating resolution of cardiogenic shock compared to placebo The duration of cardiogenic shock compared to placebo
Trial Locations
- Locations (102)
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
MidWest Cardiology Research Foundation
🇺🇸Columbus, Ohio, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Victoria Heart Institute Foundation
🇨🇦Victoria, British Columbia, Canada
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
Watson Clinic, LLP
🇺🇸Lakeland, Florida, United States
The Heart Group, PC
🇺🇸Mobile, Alabama, United States
St. Mary's Duluth Clinic Health System
🇺🇸Duluth, Minnesota, United States
Saint Louis University
🇺🇸St. Louis, Missouri, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Northeast Cardiology Associates
🇺🇸Bangor, Maine, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Lenox Hill Heart and Vascular Institute of New York
🇺🇸New York, New York, United States
John H. Stroger Jr. Hospital of Cook County
🇺🇸Chicago, Illinois, United States
University of Miami School of Medicine
🇺🇸Miami, Florida, United States
Mediquest Research Group
🇺🇸Ocala, Florida, United States
Trinity Medical Center
🇺🇸Rock Island, Illinois, United States
Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Emory Crawford Long Hospital
🇺🇸Atlanta, Georgia, United States
Iowa Health, Des Moines
🇺🇸Des Moines, Iowa, United States
Mt. Sinai Medical Center
🇺🇸Miami, Florida, United States
BryanLGH Heart Institute
🇺🇸Lincoln, Nebraska, United States
University of Iowa Hospital
🇺🇸Iowa City, Iowa, United States
Rochester Cardio-Pulmonary Group, P.C.
🇺🇸Rochester, New York, United States
Health First Clinical Research Institute
🇺🇸Melbourne, Florida, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Cardiovascular Center of Sarasota
🇺🇸Sarasota, Florida, United States
Parkview Research Center
🇺🇸Fort Wayne, Indiana, United States
Sparks Regional Medical Center
🇺🇸Fort Smith, Arizona, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Iowa Heart Centre
🇺🇸Des Moines, Iowa, United States
Heart Care Midwest
🇺🇸Peoria, Illinois, United States
Royal Alexandria Hospital
🇨🇦Edmonton, Alberta, Canada
Spectrum Health Hospitals
🇺🇸Grand Rapids, Michigan, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
Guthrie Clinic
🇺🇸Sayre, Pennsylvania, United States
Fletcher Allen Healthcare
🇺🇸Burlington, Vermont, United States
Mission Hospitals
🇺🇸Asheville, North Carolina, United States
Sanger Clinic
🇺🇸Charlotte, North Carolina, United States
The Heart Care Group
🇺🇸Allentown, Pennsylvania, United States
South Carolina Heart Center
🇺🇸Columbia, South Carolina, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
St. Thomas Cardiology Consultants
🇺🇸Nashville, Tennessee, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Mayo Clinic Minnesota
🇺🇸Rochester, Minnesota, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Providence Heart & Vascular Institute
🇺🇸Portland, Oregon, United States
Hamilton Health Sciences, General Site
🇨🇦Hamilton, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of Ottawa
🇨🇦Ottawa, Ontario, Canada
Banner Baywood Heart Hospital
🇺🇸Mesa, Arizona, United States
Central Arkansas Cardiovascular Research Group (CACRG)
🇺🇸Little Rock, Arkansas, United States
Stanford University School of Medicine
🇺🇸Palo Alto, California, United States
Desert Cardiology
🇺🇸Rancho Mirage, California, United States
South Denver Cardiology Associates, PC
🇺🇸Littleton, Colorado, United States
Florida Cardiovascular Research Center
🇺🇸Atlantis, Florida, United States
Interventional Cardiovascular Research - Lahey Clinic
🇺🇸Burlington, Massachusetts, United States
Fallon Cardiology - St. Vincent Hospital
🇺🇸Worchester, Massachusetts, United States
Nisus Research at Northern Michigan Hospital
🇺🇸Petoskey, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
LeBauer Cardiovascular Research
🇺🇸Greensboro, North Carolina, United States
Cooper Health System
🇺🇸Camden, New Jersey, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Cardiology Associates of Schenectady
🇺🇸Schenectady, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Johnson City Medical Center
🇺🇸Johnson City, Tennessee, United States
University of Texas Medical School
🇺🇸Houston, Texas, United States
Vancouver Hospital and Health Sciences Centre
🇨🇦Vancouver, British Columbia, Canada
Ben Taub General Hospital, Baylor College of Medicine
🇺🇸Houston, Texas, United States
Calgary Heart Centre Alberta
🇨🇦Calgary, Alberta, Canada
Southlake Regional Health Centre
🇨🇦Newmarket, Ontario, Canada
St. Boniface General Hospital
🇨🇦Winnipeg, Manitoba, Canada
NB Heart Centre
🇨🇦St. John, New Brunswick, Canada
Trilium Health Centre
🇨🇦Mississauga, Ontario, Canada
University of Alberta
🇨🇦Edmonton, Alberta, Canada
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Cardiology Research - QEII Health Science Centre
🇨🇦Halifax, Nova Scotia, Canada
QEII Health Science Centre - Cardiology Research
🇨🇦Halifax, Nova Scotia, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
University Health Network - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
St. Michael's Hospital Toronto
🇨🇦Toronto, Ontario, Canada
Quebec Heart Institute
🇨🇦Quebec, Canada
Mercy General Hospital
🇺🇸Sacramento, California, United States
Orlando Regional Medical Center
🇺🇸Orlando, Florida, United States
University of Michigan Health Systems
🇺🇸Ann Arbor, Michigan, United States
UNC Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Forsyth Medical Center
🇺🇸Winston-Salem, North Carolina, United States