Sodium Nitrite in Acute Myocardial Infarction

Acute Myocardial Infarction Clinical Trial

Official title:

A Safety and Efficacy Evaluation of Sodium Nitrite Injection for the Prevention of Ischemia-Reperfusion Injury Associated With Acute Myocardial Infarction.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00924118
• Other study ID #: NA_00023049
• Status: Completed
• Phase: Phase 2
• Start date: July 2009
• Est. completion date: June 2016

Study information

• Verified date: April 2018
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the intravenous infusion of sodium nitrite safely prevents ischemia-reperfusion injury in subjects with acute myocardial infarction resulting in improved left ventricular function.

Description:

Despite reperfusion therapies, significant myocardial injury continues to occur from ischemic-reperfusion injury. Studies in animal models of acute myocardial infarction suggest that an infusion of sodium nitrite, which is nonenzymatically converted to nitric oxide in the setting of ischemia, significantly reduces ischemia-reperfusion injury resulting in smaller infarcts and improved left ventricular function. The objectives of this phase 2 trial are to determine the tolerability and safety of a 48-hour infusion of sodium nitrite in patients with an acute ST-segment elevation myocardial infarction receiving percutaneous coronary intervention. The efficacy of a 48-hour infusion of sodium nitrite will be determined by noninvasive imaging to determine infarct size and left ventricular function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

• Acute ST segment elevation myocardial infarction

• Eligible for percutaneous coronary intervention

Exclusion Criteria:

• Cardiogenic shock

• Cardiac arrest

• Prior infarct in the infarct related artery

• Hemoglobinopathy, Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction
• Reperfusion Injury

Intervention

Drug:
• Sodium Nitrite
Subjects assigned to sodium nitrite will receive an initial infusion of 6 nmol/min/kg for 48 hours. After the first six subjects have been enrolled (3 active drug, 3 control) and if there are no dose limiting toxicities, additional cohorts of six subjects each will be randomized to escalating doses of sodium nitrite versus control for a total of 30 subjects.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Hope Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (3)

Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ. Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest. 2005 May;115(5):1232-40. Epub 2005 Apr 14. — View Citation

Gonzalez FM, Shiva S, Vincent PS, Ringwood LA, Hsu LY, Hon YY, Aletras AH, Cannon RO 3rd, Gladwin MT, Arai AE. Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction. Circulation. 2008 Jun 10;117(23):2986-94. doi: 10.1161/CIRCULATIONAHA.107.748814. Epub 2008 Jun 2. — View Citation

Rassaf T, Flögel U, Drexhage C, Hendgen-Cotta U, Kelm M, Schrader J. Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of cardiac energetics and function. Circ Res. 2007 Jun 22;100(12):1749-54. Epub 2007 May 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ischemia Area at Risk as Determined by Paired Single-photon Computed Tomography Studies With Technetium Tc99m Sestamibi.	Measured as percentage of left ventricle	4-5 days from enrollment
Secondary	Left Ventricular Infarct Size	Left ventricular infarct size by Magnetic Resonance Imaging (MRI). Calculated percentage of the left ventricular mass by MRI that has undergone infarction.	4-5 days following enrollment