A Study of the Safety and Efficacy of Nitric Oxide Reduction in Patients With Cardiogenic Shock After a Heart Attack
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Outcome Measures
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 []
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed myocardial infarction (heart attack)
-
Confirmed persistent cardiogenic shock
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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)
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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
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Other cause of shock (not heart attack)
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Shock due to heart valve disease
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Severe heart valve disease
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Right sided heart failure
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Shock due to arrhythmia (irregular heart rhythm)
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Severe kidney disease
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Aortic dissection (tear in aorta)
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Adult respiratory distress syndrome (ARDS) (severe lung inflammation)
-
Severe brain damage
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Severe irreversible multi-system failure (failure of multiple body organs)
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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)
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Age younger than 18 years
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Requirement for emergency coronary artery bypass grafting (CABG) or infarct-related artery occlusion (heart attack artery completely blocked)
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Ongoing or recent participation in another clinical trial of an investigational drug
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Heart Group, PC | Mobile | Alabama | United States | 36608 |
| 2 | Sparks Regional Medical Center | Fort Smith | Arizona | United States | 72901 |
| 3 | Banner Baywood Heart Hospital | Mesa | Arizona | United States | 85206 |
| 4 | Mayo Clinic Hospital | Phoenix | Arizona | United States | 85043 |
| 5 | Central Arkansas Cardiovascular Research Group (CACRG) | Little Rock | Arkansas | United States | 72205 |
| 6 | Los Angeles Cardiology Associates | Los Angeles | California | United States | 90017 |
| 7 | University of Southern California, LAC + USC Medical Center | Los Angeles | California | United States | 90033 |
| 8 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 9 | Stanford University School of Medicine | Palo Alto | California | United States | 94305-5406 |
| 10 | Desert Cardiology | Rancho Mirage | California | United States | 92270 |
| 11 | Mercy General Hospital | Sacramento | California | United States | 95819 |
| 12 | South Denver Cardiology Associates, PC | Littleton | Colorado | United States | 80120 |
| 13 | Christiana Care Health Services | Newark | Delaware | United States | 19718 |
| 14 | Washington Hospital Center | Washington | District of Columbia | United States | 20010-2975 |
| 15 | Florida Cardiovascular Research Center | Atlantis | Florida | United States | 33462 |
| 16 | Watson Clinic, LLP | Lakeland | Florida | United States | 33805 |
| 17 | Health First Clinical Research Institute | Melbourne | Florida | United States | 32901 |
| 18 | University of Miami School of Medicine | Miami | Florida | United States | 33136 |
| 19 | Mt. Sinai Medical Center | Miami | Florida | United States | 33140 |
| 20 | Mediquest Research Group | Ocala | Florida | United States | 34471 |
| 21 | Orlando Regional Medical Center | Orlando | Florida | United States | 32806 |
| 22 | Cardiovascular Center of Sarasota | Sarasota | Florida | United States | 34239 |
| 23 | Emory Crawford Long Hospital | Atlanta | Georgia | United States | 30308 |
| 24 | John H. Stroger Jr. Hospital of Cook County | Chicago | Illinois | United States | 60612 |
| 25 | Heart Care Midwest | Peoria | Illinois | United States | 61603 |
| 26 | Trinity Medical Center | Rock Island | Illinois | United States | 61201 |
| 27 | Parkview Research Center | Fort Wayne | Indiana | United States | 46805 |
| 28 | Iowa Health, Des Moines | Des Moines | Iowa | United States | 50309 |
| 29 | Iowa Heart Centre | Des Moines | Iowa | United States | 50314 |
| 30 | University of Iowa Hospital | Iowa City | Iowa | United States | 52242 |
| 31 | University of Kansas Hospital | Kansas City | Kansas | United States | 66160 |
| 32 | University of Kentucky | Lexington | Kentucky | United States | 40536-0200 |
| 33 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121 |
| 34 | Northeast Cardiology Associates | Bangor | Maine | United States | 04401 |
| 35 | Maine Medical Center | Portland | Maine | United States | 04102 |
| 36 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 37 | Boston Medical Center | Boston | Massachusetts | United States | 02118 |
| 38 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 39 | Interventional Cardiovascular Research - Lahey Clinic | Burlington | Massachusetts | United States | 01805 |
| 40 | University of Massachusetts Medical School | Worcester | Massachusetts | United States | 01655 |
| 41 | Fallon Cardiology - St. Vincent Hospital | Worchester | Massachusetts | United States | 01608 |
| 42 | University of Michigan Health Systems | Ann Arbor | Michigan | United States | 48109-0311 |
| 43 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 44 | Spectrum Health Hospitals | Grand Rapids | Michigan | United States | 49525 |
| 45 | Nisus Research at Northern Michigan Hospital | Petoskey | Michigan | United States | 49770 |
| 46 | William Beaumont Hospital | Royal Oak | Michigan | United States | 48073-6769 |
| 47 | St. Mary's Duluth Clinic Health System | Duluth | Minnesota | United States | 55805 |
| 48 | Mayo Clinic Minnesota | Rochester | Minnesota | United States | 55905 |
| 49 | Saint Louis University | St. Louis | Missouri | United States | 63110 |
| 50 | Washington University | St. Louis | Missouri | United States | 63110 |
| 51 | BryanLGH Heart Institute | Lincoln | Nebraska | United States | 68516 |
| 52 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-2265 |
| 53 | Cooper Health System | Camden | New Jersey | United States | 08103 |
| 54 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
| 55 | Lenox Hill Heart and Vascular Institute of New York | New York | New York | United States | 10021 |
| 56 | Mount Sinai Medical Center | New York | New York | United States | 10029 |
| 57 | Rochester Cardio-Pulmonary Group, P.C. | Rochester | New York | United States | 14621 |
| 58 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 59 | Cardiology Associates of Schenectady | Schenectady | New York | United States | 12309 |
| 60 | Mission Hospitals | Asheville | North Carolina | United States | 28801 |
| 61 | UNC Chapel Hill | Chapel Hill | North Carolina | United States | 27599-7075 |
| 62 | Sanger Clinic | Charlotte | North Carolina | United States | 28203 |
| 63 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 64 | LeBauer Cardiovascular Research | Greensboro | North Carolina | United States | 27401 |
| 65 | Forsyth Medical Center | Winston-Salem | North Carolina | United States | 27103 |
| 66 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 67 | MidWest Cardiology Research Foundation | Columbus | Ohio | United States | 43214 |
| 68 | The Oregon Clinic | Portland | Oregon | United States | 97213-2281 |
| 69 | Providence Heart & Vascular Institute | Portland | Oregon | United States | 97225 |
| 70 | The Heart Care Group | Allentown | Pennsylvania | United States | 18106 |
| 71 | Penn State Hershey Medical Center | Hershey | Pennsylvania | United States | 17033-0850 |
| 72 | Lancaster General Hospital | Lancaster | Pennsylvania | United States | 17603 |
| 73 | Allegheny General Hospital | Pittsburgh | Pennsylvania | United States | 15212 |
| 74 | Guthrie Clinic | Sayre | Pennsylvania | United States | 18830 |
| 75 | The Miriam Hospital | Providence | Rhode Island | United States | 02906 |
| 76 | South Carolina Heart Center | Columbia | South Carolina | United States | 29204 |
| 77 | Johnson City Medical Center | Johnson City | Tennessee | United States | 37601 |
| 78 | St. Thomas Cardiology Consultants | Nashville | Tennessee | United States | 37205 |
| 79 | Ben Taub General Hospital, Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 80 | The Methodist Hospital | Houston | Texas | United States | 77030 |
| 81 | University of Texas Medical School | Houston | Texas | United States | 77030 |
| 82 | LDS Hospital | Salt Lake City | Utah | United States | 84143 |
| 83 | Fletcher Allen Healthcare | Burlington | Vermont | United States | 05401 |
| 84 | Calgary Heart Centre Alberta | Calgary | Alberta | Canada | T2N 2T9 |
| 85 | Royal Alexandria Hospital | Edmonton | Alberta | Canada | T5H3V9 |
| 86 | University of Alberta | Edmonton | Alberta | Canada | T6G 2B7 |
| 87 | Vancouver Hospital and Health Sciences Centre | Vancouver | British Columbia | Canada | V5Z 1L8 |
| 88 | St. Paul's Hospital | Vancouver | British Columbia | Canada | V6Z 1Y6 |
| 89 | Victoria Heart Institute Foundation | Victoria | British Columbia | Canada | V8R 4R2 |
| 90 | St. Boniface General Hospital | Winnipeg | Manitoba | Canada | R2H 2A6 |
| 91 | NB Heart Centre | St. John | New Brunswick | Canada | E2L 4L2 |
| 92 | Cardiology Research - QEII Health Science Centre | Halifax | Nova Scotia | Canada | B3H 3A7 |
| 93 | QEII Health Science Centre - Cardiology Research | Halifax | Nova Scotia | Canada | B3H 3A7 |
| 94 | Hamilton Health Sciences, General Site | Hamilton | Ontario | Canada | L8L 2X2 |
| 95 | London Health Sciences Centre | London | Ontario | Canada | N6A 4G5 |
| 96 | Trilium Health Centre | Mississauga | Ontario | Canada | L5B 2P7 |
| 97 | Southlake Regional Health Centre | Newmarket | Ontario | Canada | L3Y 2R2 |
| 98 | University of Ottawa | Ottawa | Ontario | Canada | K1Y 4W7 |
| 99 | St. Michael's Hospital Toronto | Toronto | Ontario | Canada | M5B 1W8 |
| 100 | University Health Network - Toronto General Hospital | Toronto | Ontario | Canada | M5G 2C4 |
| 101 | Montreal Heart Institute | Montreal | Quebec | Canada | H1T 1C8 |
| 102 | Quebec Heart Institute | Quebec | Canada | G1V 4G5 |
Sponsors and Collaborators
- Arginox Pharmaceuticals
Investigators
- Study Chair: Judith S. Hochman, M.D., NYU Langone Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ARG-CS3-001