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

Shock, Cardiogenic Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00112281
• Other study ID #: ARG-CS3-001
• Status: Terminated
• Phase: Phase 3
• First received: June 1, 2005
• Last updated: August 2, 2006
• Start date: May 2005
• Est. completion date: January 2007

Study information

• Verified date: May 2005
• Source: Arginox Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 658
• Est. completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Myocardial Infarction
• Shock
• Shock, Cardiogenic

Intervention

Drug:
• Tilarginine Acetate Injection intravenous infusion

Locations

Country	Name	City	State
Canada	Calgary Heart Centre Alberta	Calgary	Alberta
Canada	Royal Alexandria Hospital	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta
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	Montreal Heart Institute	Montreal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	University of Ottawa	Ottawa	Ontario
Canada	Quebec Heart Institute	Quebec
Canada	NB Heart Centre	St. John	New Brunswick
Canada	St. Michael's Hospital Toronto	Toronto	Ontario
Canada	University Health Network - Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver Hospital and Health Sciences Centre	Vancouver	British Columbia
Canada	Victoria Heart Institute Foundation	Victoria	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
United States	The Heart Care Group	Allentown	Pennsylvania
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	Mission Hospitals	Asheville	North Carolina
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Florida Cardiovascular Research Center	Atlantis	Florida
United States	Northeast Cardiology Associates	Bangor	Maine
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Fletcher Allen Healthcare	Burlington	Vermont
United States	Interventional Cardiovascular Research - Lahey Clinic	Burlington	Massachusetts
United States	Cooper Health System	Camden	New Jersey
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Sanger Clinic	Charlotte	North Carolina
United States	John H. Stroger Jr. Hospital of Cook County	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	South Carolina Heart Center	Columbia	South Carolina
United States	MidWest Cardiology Research Foundation	Columbus	Ohio
United States	Iowa Health, Des Moines	Des Moines	Iowa
United States	Iowa Heart Centre	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	St. Mary's Duluth Clinic Health System	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Sparks Regional Medical Center	Fort Smith	Arizona
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	LeBauer Cardiovascular Research	Greensboro	North Carolina
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
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	University of Iowa Hospital	Iowa City	Iowa
United States	Johnson City Medical Center	Johnson City	Tennessee
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Watson Clinic, LLP	Lakeland	Florida
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	University of Kentucky	Lexington	Kentucky
United States	BryanLGH Heart Institute	Lincoln	Nebraska
United States	Central Arkansas Cardiovascular Research Group (CACRG)	Little Rock	Arkansas
United States	South Denver Cardiology Associates, PC	Littleton	Colorado
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Los Angeles Cardiology Associates	Los Angeles	California
United States	University of Southern California, LAC + USC Medical Center	Los Angeles	California
United States	Health First Clinical Research Institute	Melbourne	Florida
United States	Banner Baywood Heart Hospital	Mesa	Arizona
United States	Mt. Sinai Medical Center	Miami	Florida
United States	University of Miami School of Medicine	Miami	Florida
United States	The Heart Group, PC	Mobile	Alabama
United States	St. Thomas Cardiology Consultants	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
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	Christiana Care Health Services	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Mediquest Research Group	Ocala	Florida
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Orlando Regional Medical Center	Orlando	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	Heart Care Midwest	Peoria	Illinois
United States	Nisus Research at Northern Michigan Hospital	Petoskey	Michigan
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Providence Heart & Vascular Institute	Portland	Oregon
United States	The Oregon Clinic	Portland	Oregon
United States	The Miriam Hospital	Providence	Rhode Island
United States	Desert Cardiology	Rancho Mirage	California
United States	Mayo Clinic Minnesota	Rochester	Minnesota
United States	Rochester Cardio-Pulmonary Group, P.C.	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	Trinity Medical Center	Rock Island	Illinois
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Mercy General Hospital	Sacramento	California
United States	LDS Hospital	Salt Lake City	Utah
United States	Cardiovascular Center of Sarasota	Sarasota	Florida
United States	Guthrie Clinic	Sayre	Pennsylvania
United States	Cardiology Associates of Schenectady	Schenectady	New York
United States	Saint Louis University	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	Washington Hospital Center	Washington	District of Columbia
United States	Forsyth Medical Center	Winston-Salem	North Carolina
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	Fallon Cardiology - St. Vincent Hospital	Worchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Arginox Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause mortality at 30 days post randomization
Secondary	Number of patients demonstrating resolution of cardiogenic shock compared to placebo
Secondary	The duration of cardiogenic shock compared to placebo