Contact information
Type
Scientific
Primary contact
Prof Anthony Mathur
ORCID ID
Contact details
London Chest Hospital
Victoria Park Site
Bonner Road
London
E2 9JX
United Kingdom
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a.mathur@qmul.ac.uk
Additional identifiers
EudraCT number
2011-000721-77
ClinicalTrials.gov number
Protocol/serial number
12117
Study information
Scientific title
A randomised, double-blind, placebo-controlled trial assessing the safety and efficacy of intracoronary NITRITE infusion during Acute Myocardial Infarction
Acronym
NITRITE-AMI
Study hypothesis
Despite advances in the treatment of heart attacks such as reopening of the blocked artery (primary angioplasty), the complications and death rates from failure of the heart to pump adequately remain high. The size of the heart attack is the major determinant of these adverse outcomes. Whilst reopening the artery allows blood to flow to the area of the heart starved of oxygen, this process also causes damage itself (reperfusion injury) and increases the size of the heart attack.
It has been shown that nitrite protects against reperfusion injury in models of heart attack. We will therefore perform a trial to investigate whether during a heart attack, an infusion of nitrite into the damaged artery protects against reperfusion injury and reduces heart attack size.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12117
Ethics approval
Committee:- NRES Committee London-West London, 08 November 2011, REC reference: 11/LO/1500
Study design
Randomised single centre double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Topic: Cardiovascular; Subtopic: Cardiovascular (all Subtopics); Disease: Atherothrombosis
Intervention
Sodium Chloride, Placebo
10mls Intra-coronary at time of PPCI; Sodium Nitrite, Study IMP
10mls 1.8% intra-coronary during PPCI
The experimental intervention is a bolus of sodium nitrite solution (1.8 micromol in 10 ml (pre-diluted in 0.9% sodium chloride in a syringe) which will be delivered over 30 seconds via intracoronary injection initiated during the re-establishment of antegrade epicardial flow with PPCI.
The control intervention is a bolus of 0.9% sodium chloride solution (prepared with an identical appearance to the sodium nitrite).
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Creatine Kinase AUC first 48 hours after PPCI
Secondary outcome measures
1. Infarct size on CMR; Timepoint(s): 48 hours and 6 months
2. Myocardial salvage index (MSI) on CMR; Timepoint(s): 48 hours
3. Troponin T AUC; Timepoint(s): 1st 48 hours after PPCI
Overall trial start date
10/04/2012
Overall trial end date
10/02/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients aged at least 18 years, upper age limit 80 years, male and female
2. Acute ST-elevation myocardial infarction with ECG showing at least 2 mm of ST segment elevation in 2 or more limb leads or 1mm in 2 or more contiguous chest leads, or new left bundle branch block
3. Haemodynamically stable
4. Estimated symptom to balloon or aspiration time < 6 hours
5. A signed and dated written informed consent prior to admission to the study
6. Angiographicallly
6.1. Primary Percutaneous Coronary Intervention (PPCI) indicated for revascularisation
6.2. Single epicardial artery to be treated
6.3. Expected ability to use the over the wire balloon for delivery of nitrite
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
UK Sample Size: 80
Participant exclusion criteria
1. Patients already on nitrate Treatment (Nicorandil, ISMN)
2. Previous history of myocardial infarction (MI) or systolic dysfunction
3. Previous coronary artery bypass surgery (CABG)
4. Subjects presenting with cardiogenic shock (SBP <80 mmHg for >30 minutes, or requiring inotropes or emergency IntraAortic
Balloon Pump (IABP) for hypotension treatment) or cardiopulmonary resuscitation
5. Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer
6. Current life-threatening condition other than vascular disease that may prevent a subject completing the study
7. 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
8. Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subjects unwillingness to comply with all study-related procedures)
9. Severe acute infection, or significant trauma (burns, fractures)
10. Pregnancy
11. Contraindications tocardiac magnetic resonance (CMR) scanning
11.1. Pacemakers, intracranial clips or other metal implants or foreign bodies
11.2. Claustrophobia
11.3. Renal Failure (eGFR<30mls/min)
12. History of alcohol or drug abuse within the past 6 months
13. History of congenital methaemoglobinaemia
14. Angiographically
14.1. Severe vessel tortuosity, diffuse disease or severe calcification is present which may impede successful delivery of the over the wire balloon
Recruitment start date
10/04/2012
Recruitment end date
10/02/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
London Chest Hospital
London
E2 9JX
United Kingdom
Sponsor information
Organisation
Barts and The London NHS Trust (UK)
Sponsor details
Joint Research Office
24-26 Walden Street
London
E1 2AN
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
NIHR (UK) - Doctoral Research Fellowship; Grant Codes: NIHR-DRF-2011-04-080
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2013 protocol in http://www.ncbi.nlm.nih.gov/pubmed/23550096
2. 2017 results in https://www.ncbi.nlm.nih.gov/pubmed/27683405
Publication citations
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Protocol
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, 3, 4, doi: 10.1136/bmjopen-2013-002813.