Clinical trial NCT00112281: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Shock, Cardiogenic
Keywords: shock, cardiogenic, "myocardial infarction"
Lead sponsor: Arginox Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2005-06-02
Enrollment: 658
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: All cause mortality at 30 days post randomization
Secondary outcomes:
measure: Number of patients demonstrating resolution of cardiogenic shock compared to placebo
measure: The duration of cardiogenic shock compared to placebo
Other outcomes:
Locations:
city: Mobile
country: United States
facility: The Heart Group, PC
state: Alabama
city: Fort Smith
country: United States
facility: Sparks Regional Medical Center
state: Arizona
city: Mesa
country: United States
facility: Banner Baywood Heart Hospital
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Little Rock
country: United States
facility: Central Arkansas Cardiovascular Research Group (CACRG)
state: Arkansas
city: Los Angeles
country: United States
facility: Los Angeles Cardiology Associates
state: California
city: Los Angeles
country: United States
facility: University of Southern California, LAC + USC Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Rancho Mirage
country: United States
facility: Desert Cardiology
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates, PC
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Atlantis
country: United States
facility: Florida Cardiovascular Research Center
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic, LLP
state: Florida
city: Melbourne
country: United States
facility: Health First Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Miami
country: United States
facility: Mt. Sinai Medical Center
state: Florida
city: Ocala
country: United States
facility: Mediquest Research Group
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Medical Center
state: Florida
city: Sarasota
country: United States
facility: Cardiovascular Center of Sarasota
state: Florida
city: Atlanta
country: United States
facility: Emory Crawford Long Hospital
state: Georgia
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital of Cook County
state: Illinois
city: Peoria
country: United States
facility: Heart Care Midwest
state: Illinois
city: Rock Island
country: United States
facility: Trinity Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Des Moines
country: United States
facility: Iowa Health, Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Heart Centre
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Bangor
country: United States
facility: Northeast Cardiology Associates
state: Maine
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Interventional Cardiovascular Research - Lahey Clinic
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Worchester
country: United States
facility: Fallon Cardiology - St. Vincent Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Petoskey
country: United States
facility: Nisus Research at Northern Michigan Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Duluth
country: United States
facility: St. Mary's Duluth Clinic Health System
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Lincoln
country: United States
facility: BryanLGH Heart Institute
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: Cooper Health System
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Lenox Hill Heart and Vascular Institute of New York
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester Cardio-Pulmonary Group, P.C.
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Schenectady
country: United States
facility: Cardiology Associates of Schenectady
state: New York
city: Asheville
country: United States
facility: Mission Hospitals
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Sanger Clinic
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: LeBauer Cardiovascular Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: MidWest Cardiology Research Foundation
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Portland
country: United States
facility: Providence Heart & Vascular Institute
state: Oregon
city: Allentown
country: United States
facility: The Heart Care Group
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Columbia
country: United States
facility: South Carolina Heart Center
state: South Carolina
city: Johnson City
country: United States
facility: Johnson City Medical Center
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Cardiology Consultants
state: Tennessee
city: Houston
country: United States
facility: Ben Taub General Hospital, Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Medical School
state: Texas
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Healthcare
state: Vermont
city: Calgary
country: Canada
facility: Calgary Heart Centre Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandria Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Hospital and Health Sciences Centre
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Heart Institute Foundation
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: St. John
country: Canada
facility: NB Heart Centre
state: New Brunswick
city: Halifax
country: Canada
facility: Cardiology Research - QEII Health Science Centre
state: Nova Scotia
city: Halifax
country: Canada
facility: QEII Health Science Centre - Cardiology Research
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences, General Site
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Mississauga
country: Canada
facility: Trilium Health Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital Toronto
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec
country: Canada
facility: Quebec Heart Institute
Study officials:
affiliation: NYU Langone Health
name: Judith S. Hochman, M.D.
role: STUDY_CHAIR
References:
citation: 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.