Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)
1 Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
2 Centre for Healthcare Randomised Trials (CHaRT) Health Services Research Unit, University of Aberdeen, Health Sciences Building, Foresterhill, Aberdeen AB25 2ZD, UK
3 Cardiovascular Sciences Research Centre, Cranmer Terrace, London SW17 0RE, UK
4 Cardiology Department Atkinson Morley Wing, St Georges Healthcare NHS Trust, Blackshaw Road, London SW17 0Q, UK
5 Brighton and Sussex University Hospitals, Cardiology Research Unit, 1 Abbey Road, Brighton BN2 1ES, UK
6 Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South SA 5011, Australia
7 Centre for Cardiovascular Sciences College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
8 Centre for Cardiovascular Science, The University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SU, UK
Journal of Translational Medicine 2013, 11:116 doi:10.1186/1479-5876-11-116Published: 6 May 2013
Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial.
Methods and outcomes
The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6–8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6–8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6–8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6–8 days and six months.
Funding, ethics and regulatory approvals
This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26).