title: The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial.
abstract: BACKGROUND
  Acute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF) and improving clinical outcomes. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is currently no effective therapy. Extensive preclinical evidence exists to suggest that sodium nitrite (as a source of endogenous nitric oxide) is an effective therapeutic strategy for preventing myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether sodium nitrite reduces reperfusion injury and subsequent infarct size in patients undergoing PPCI for MI.
  
  
  METHODS
  NITRITE-AMI is a double-blind, randomised, single-centre, placebo-controlled trial to determine whether intracoronary nitrite injection reduces infarct size in patients with myocardial infarction undergoing primary angioplasty. The study will enrol 80 patients presenting with ST-elevation myocardial infarction. Patients will be randomised to receive either a bolus of intracoronary sodium nitrite or placebo (sodium chloride) at the time of PPCI. The primary outcome is infarct size assessed by creatine kinase area under the curve (AUC) over 48 h. Secondary endpoints include troponin T AUC and infarct size, LV dimensions and myocardial salvage index assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation, the safety and tolerability of intracoronary nitrite, and 1 year major adverse cardiac events.
  
  
  BACKGROUND
  The study is approved by the local ethics committee (NRES Committee London West London: 11/LO/1500) and by the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010-022460-12). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.
  
  
  BACKGROUND
  United Kingdom Clinical Research Network (Study ID 12117), http://clinicaltrials.gov (NCT01584453) and Current Controlled Trials (ISRCTN:38736987).
authors.affiliation: Centre of Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Queen Mary University, London, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Andiapen
authors.forename: T J A
authors.initials: TJ
authors.lastname: Van-Eijl
authors.forename: A J
authors.initials: AJ
authors.lastname: Webb
authors.forename: S
authors.initials: S
authors.lastname: Antoniou
authors.forename: R J
authors.initials: RJ
authors.lastname: Schilling
authors.forename: A
authors.initials: A
authors.lastname: Ahluwalia
authors.forename: A
authors.initials: A
authors.lastname: Mathur
references.citation: J Am Soc Nephrol. 2007 Feb;18(2):570-80
references.pmid: 17202421
references.citation: J Am Coll Cardiol. 2006 Jun 6;47(11):2180-6
references.pmid: 16750682
references.citation: N Engl J Med. 2008 May 22;358(21):2218-30
references.pmid: 18499566
references.citation: JAMA. 2010 Jun 2;303(21):2148-55
references.pmid: 20516415
references.citation: Heart. 2008 Jun;94(6):730-6
references.pmid: 18070953
references.citation: Am Heart J. 2010 Dec;160(6 Suppl):S16-21
references.pmid: 21147287
references.citation: Circulation. 1999 Jul 6;100(1):14-20
references.pmid: 10393675
references.citation: Eur Heart J. 2010 Apr;31(8):943-57
references.pmid: 19933242
references.citation: J Biol Chem. 2008 Dec 5;283(49):33927-34
references.pmid: 18835812
references.citation: Circulation. 2008 Jun 10;117(23):2986-94
references.pmid: 18519850
references.citation: Nat Rev Drug Discov. 2008 Feb;7(2):156-67
references.pmid: 18167491
references.citation: J Clin Invest. 2005 May;115(5):1232-40
references.pmid: 15841216
references.citation: Circulation. 2005 Oct 4;112(14):2143-8
references.pmid: 16186417
references.citation: Lancet. 2003 Jan 4;361(9351):13-20
references.pmid: 12517460
references.citation: Nat Chem Biol. 2005 Oct;1(5):290-7
references.pmid: 16408059
references.citation: JAMA. 2000 Jun 14;283(22):2941-7
references.pmid: 10865271
references.citation: Heart. 2010 May;96(9):656-61
references.pmid: 19910292
references.citation: Hypertension. 2008 Mar;51(3):784-90
references.pmid: 18250365
references.citation: J Pathol. 2000 Feb;190(3):255-66
references.pmid: 10685060
references.citation: Am J Physiol. 1998 Dec;275(6):H2300-7
references.pmid: 9843832
references.citation: J Mol Cell Cardiol. 2007 Feb;42(2):271-9
references.pmid: 16839566
references.citation: JACC Cardiovasc Interv. 2008 Aug;1(4):415-23
references.pmid: 19463339
references.citation: JACC Cardiovasc Imaging. 2011 Feb;4(2):150-6
references.pmid: 21329899
references.citation: N Engl J Med. 2008 Jul 31;359(5):473-81
references.pmid: 18669426
references.citation: Neth Heart J. 2010 Mar;18(3):122-8
references.pmid: 20390062
references.citation: Am J Cardiol. 2008 Jul 1;102(1):1-5
references.pmid: 18572027
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13683-8
references.pmid: 15347817
references.citation: J Am Coll Cardiol. 2004 Oct 19;44(8):1533-42
references.pmid: 15489082
references.citation: J Mol Cell Cardiol. 2006 Jan;40(1):16-23
references.pmid: 16288777
references.citation: Pharmacol Ther. 2005 May;106(2):147-62
references.pmid: 15866317
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10256-61
references.pmid: 18632562
references.citation: J Cell Sci. 2003 Jan 1;116(Pt 1):9-15
references.pmid: 12456711
references.citation: J Am Coll Cardiol. 2002 Jan 2;39(1):30-6
references.pmid: 11755283
references.citation: Eur Heart J. 2007 Jul;28(14):1750-8
references.pmid: 17586811
references.citation: Nat Med. 2003 Dec;9(12):1498-505
references.pmid: 14595407
references.citation: JACC Cardiovasc Imaging. 2009 Jul;2(7):825-31
references.pmid: 19608131
references.citation: Clin Chim Acta. 1983 Mar 14;128(2-3):329-35
references.pmid: 6851141
references.citation: J Mol Cell Cardiol. 2001 Nov;33(11):1897-918
references.pmid: 11708836
references.citation: Eur Heart J. 2009 Apr;30(7):757-64
references.pmid: 19202155
references.citation: Crit Care Med. 1991 Feb;19(2):244-52
references.pmid: 1846569
references.citation: Eur Heart J. 2009 Sep;30(18):2193-203
references.pmid: 19726437
references.citation: J Biol Chem. 2008 Jun 27;283(26):17855-63
references.pmid: 18424432
references.citation: Curr Control Trials Cardiovasc Med. 2005 Aug 23;6:12
references.pmid: 16115321
references.citation: Circulation. 2008 Feb 5;117(5):670-7
references.pmid: 18212289
references.citation: JAMA. 2005 Mar 23;293(12):1477-84
references.pmid: 15784871
references.citation: J Mol Cell Cardiol. 2007 Oct;43(4):437-44
references.pmid: 17765919
references.citation: Stroke. 2006 Nov;37(11):2744-50
references.pmid: 17008610
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1386-91
references.pmid: 14742866
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651-5
references.pmid: 1675786
references.citation: Nat Rev Cardiol. 2009 Apr;6(4):283-91
references.pmid: 19352332
references.citation: Int J Cardiol. 2005 Apr 20;100(2):179-90
references.pmid: 15823623
references.citation: N Engl J Med. 2007 Sep 13;357(11):1121-35
references.pmid: 17855673
references.citation: Heart. 2005 Dec;91(12):1533-6
references.pmid: 16287736
references.citation: J Biol Chem. 1997 Aug 22;272(34):21420-6
references.pmid: 9261157
references.citation: Circulation. 2007 Oct 16;116(16):1821-31
references.pmid: 17893272