A randomised, double-blind, placebo-controlled trial assessing the safety and efficacy of intracoronary NITRITE infusion during Acute Myocardial Infarction

ISRCTN ISRCTN38736987
DOI https://doi.org/10.1186/ISRCTN38736987
EudraCT/CTIS number 2011-000721-77
ClinicalTrials.gov number NCT01584453
Secondary identifying numbers 12117
Submission date
18/01/2013
Registration date
23/01/2013
Last edited
27/08/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Anthony Mathur
Scientific

London Chest Hospital
Victoria Park Site
Bonner Road
London
E2 9JX
United Kingdom

Email a.mathur@qmul.ac.uk

Study information

Study designRandomised single centre double-blind placebo-controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titleA randomised, double-blind, placebo-controlled trial assessing the safety and efficacy of intracoronary NITRITE infusion during Acute Myocardial Infarction
Study acronymNITRITE-AMI
Study objectivesDespite 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(s)Committee:- NRES Committee London-West London, 08 November 2011, REC reference: 11/LO/1500
Health condition(s) or problem(s) studiedTopic: Cardiovascular; Subtopic: Cardiovascular (all Subtopics); Disease: Atherothrombosis
InterventionSodium 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 typeOther
Primary outcome measureCreatine Kinase AUC first 48 hours after PPCI
Secondary outcome measures1. 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 study start date10/04/2012
Completion date10/02/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsUK Sample Size: 80
Key inclusion criteria1. 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
Key exclusion criteria1. 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 subject’s 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
Date of first enrolment10/04/2012
Date of final enrolment10/02/2014

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

London Chest Hospital
London
E2 9JX
United Kingdom

Sponsor information

Barts and The London NHS Trust (UK)
Hospital/treatment centre

Joint Research Office
24-26 Walden Street
London
E1 2AN
England
United Kingdom

Website http://www.bartsandthelondon.nhs.uk/
ROR logo "ROR" https://ror.org/00b31g692

Funders

Funder type

Government

NIHR (UK) - Doctoral Research Fellowship; Grant Codes: NIHR-DRF-2011-04-080

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 02/04/2013 Yes No
Results article results 01/04/2017 Yes No
Results article results 30/01/2015 27/08/2019 Yes No
HRA research summary 28/06/2023 No No

Editorial Notes

27/08/2019: ClinicalTrials.gov number added. Publication reference added.
25/09/2018: Publication reference added.