Safety and Effectiveness of Intra-coronary Nitrite in Acute Myocardial Infarction

NCT01584453 | Completed Phase 2 DMC

• 1 other identifier: 11/LO/1500
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Despite advances in the treatment of heart attacks the complications and death rates from failure of the heart to pump properly after treatment remain high. A heart attack occurs when one or more of the arteries that supply blood to the heart become blocked, causing the heart to be starved of oxygen and nutrients. This results in damage to the heart and so the the heart pumps less well. The main treatment for a heart attack is balloon treatment to open the blocked artery (called primary angioplasty). Whilst re-opening the artery is essential and allows blood to flow to the area of the heart starved of oxygen, this process also causes damage itself (called reperfusion injury) and increases the size of the heart attack further. Currently there are no treatments available that reduce this reperfusion injury. The investigators and others have shown that a substance called sodium nitrite reduces reperfusion injury in experimental models of a heart attack. The aim of this research is to perform a trial to investigate whether during a heart attack, an infusion of sodium nitrite into the damaged artery protects against reperfusion injury and reduces heart attack size in patients.

Conditions

Myocardial Infarction; Reperfusion Injury; Myocardial Ischemia; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• Infarct size measured by CK area under the curve

  AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours)

  1st 48 hours after AMI

Secondary Outcomes (9)

• Infarct size measured by Troponin T Area under the curve

  1st 48 hours post AMI

• Infarct size, assessed by CMR at 6 months ± 2 weeks.

  6 months ± 2 weeks.

• Infarct size as a proportion of area at risk measured at 48 hours by CMR.

  48 hours

• The acute safety and tolerability of intra-coronary nitrite in STEMI

  1st 48 hours

• Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation)

  12 months

Study Arms (2)

Sodium Nitrite

EXPERIMENTAL

Drug: Sodium Nitrite

Placebo

PLACEBO COMPARATOR

Drug: Sodium Chloride Placebo

Interventions

Sodium Nitrite DRUG

A bolus of sodium nitrite solution (1.8 micromol in 10 ml PRe-diluted in 0.9% sodium chloride in a syringe) will be delivered over 30-60 seconds via intracoronary injection initiated during the re-establishment of antegrade epicardial flow with PPCI.

Sodium Nitrite

Sodium Chloride Placebo DRUG

The control intervention is a bolus of 0.9% sodium chloride solution (prepared with an identical appearance to the sodium nitrite).

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged at least 18 years
• Acute STEMI with ECG showing ST-segment elevation of 1mm or more in two adjacent limb leads or 2mm or more in at least two contiguous precordial leads or new left bundle branch block;
• Haemodynamically stable
• Estimated symptom to balloon or aspiration time \< 6 hours
• Angiographically i) PPCI indicated for revascularisation ii) Single epicardial artery to be treated iii) Expected ability to use over the wire balloon

You may not qualify if:

• Patients on organic nitrate treatment (Nicorandil, isosorbide mononitrate)
• Previous history of AMI, systolic dysfunction or CABG
• Subjects presenting with cardiogenic shock (systolic blood pressure \<80 mmHg for \> 30 minutes, or requiring inotropes/emergency intra aortic balloon pump or cardiopulmonary resuscitation
• Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
• Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
• Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
• Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject's unwillingness to comply with all study-related procedures).
• Severe acute infection, or significant trauma (burns, fractures).
• Pregnancy.
• Contra-indications to CMR scanning i) Pacemakers, intracranial clips or other metal implants ii) Claustrophobia iii) Renal failure (eGFR \< 30mls/min)
• History of alcohol or drug abuse within the past 6 months.
• History of congenital methaemoglobinaemia.
• Angiographically severe vessel tortuosity, diffuse disease or severe calcification which may impede successful delivery of the the over the wire balloon.

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• Queen Mary University of London: collaborator

Study Sites (1)

London Chest Hospital

Bethnal Green, London, E2 9JX, United Kingdom

Location

Related Publications (3)

• Jones DA, Khambata RS, Andiapen M, Rathod KS, Mathur A, Ahluwalia A. Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention. Heart. 2017 Apr;103(7):508-516. doi: 10.1136/heartjnl-2016-309748. Epub 2016 Sep 28.

  PMID: 27683405 DERIVED

• Jones DA, Pellaton C, Velmurugan S, Rathod KS, Andiapen M, Antoniou S, van Eijl S, Webb AJ, Westwood MA, Parmar MK, Mathur A, Ahluwalia A. Randomized phase 2 trial of intracoronary nitrite during acute myocardial infarction. Circ Res. 2015 Jan 30;116(3):437-47. doi: 10.1161/CIRCRESAHA.116.305082. Epub 2014 Dec 15.

  PMID: 25512434 DERIVED

• Jones DA, Andiapen M, Van-Eijl TJ, Webb AJ, Antoniou S, Schilling RJ, Ahluwalia A, Mathur A. The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial. BMJ Open. 2013 Apr 2;3(4):e002813. doi: 10.1136/bmjopen-2013-002813. Print 2013.

  PMID: 23550096 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Reperfusion Injury; Myocardial Ischemia; Cardiovascular Diseases

Interventions

Sodium Nitrite

Condition Hierarchy (Ancestors)

Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Postoperative Complications

Intervention Hierarchy (Ancestors)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Anthony Mathur, FRCP, PhD

  Barts and the London NHS Trust/QMUL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 25, 2012
• Study Start: April 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: January 1, 2016
• Last Updated: November 29, 2017

Record last verified: 2015-07

Locations

GB (1)