Nitrites in Acute Myocardial Infarction (NIAMI)

Does Sodium Nitrite Administration Reduce Ischaemia-reperfusion Injury in Patients Presenting With Acute ST Segment Elevation Myocardial Infarction?

The research question to be addressed is "Does a 2.5 - 5 minute systemic intravenous injection of sodium nitrite administered immediately before opening of the infarct related artery result in significant reduction of ischaemia reperfusion injury in patients with first acute ST elevation myocardial infarction (MI)?"

Study Overview

• Status: Completed
• Conditions: Acute ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: sodium nitrite; Other: Placebo

Detailed Description

There are estimated to be 125,000 acute myocardial infarctions (heart attacks) in the UK every year. Although substantial progress has been made in reducing the infarct size by prompt opening of the infarct related artery (with thrombolytic therapy or percutaneous coronary intervention (PCI)), effective therapy to further reduce the infarct size would substantially reduce the risk of the patient subsequently developing heart failure.

There is a growing body of evidence from studies in animals that the use of nitrites may help in reducing the infarct size, although this has not been tested in man.

In this phase 2/3 study, the investigators propose to investigate the effect of sodium nitrite injection on infarct size. Eligible patients will be males aged 18 and over and females aged 55 and over, presenting within 12 hours of the onset of chest pain, who are suitable for treatment with percutaneous coronary intervention. Those who give verbal agreement to take part will receive a 2.5-5 minute injection of sodium nitrite (or placebo) immediately prior to the blocked artery being opened with percutaneous coronary intervention.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZD
    • Aberdeen Royal Infirmary
  • Brighton, United Kingdom
    • Brighton and Sussex University Hospitals NHS Trust
  • London, United Kingdom, SW17 0QT
    • St George's Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Men aged ≥18 years, women aged ≥55 years, and women <55years who are sterilised, or have had a hysterectomy or have effective contraception and thus where there is no possibility of them being pregnant; presenting within 12 hours of the onset of chest pain who have ST segment elevation of more than 1mm elevation in limb leads or 2mm elevation in two contiguous chest leads or new left bundle branch block (LBBB) and for whom the clinical decision has been made to treat with primary PCI will be eligible for enrolment. Occlusion of the culprit related artery (TIMI grade 0 or TIMI grade 1) will also be required for inclusion. Eligible patients will be of North European descent.

Exclusion criteria

• Historical or ECG evidence of previous myocardial infarction
• Patients with prior coronary artery bypass grafting (CABG)
• Prior revascularization procedure where this procedure (PCI) was performed in the same territory as the current infarct
• Known or suspected pregnancy
• Contra-indications to MRI
• Patients with cardiac arrest or cardiogenic shock
• Patients with left main coronary occlusion
• Patients with known moderate to severe renal failure (estimated GFR < 30mls/min), or liver failure
• Patients with prior thrombolysis for this event
• Patients with such Left Main disease which after PCI of their culprit lesion (culprit lesions may be located in the LAD or LCx or RCA) are likely to require CABG within the time course of the study period (6 months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sodium nitrite	Drug: sodium nitrite; sterile solution containing low dose sodium nitrite dissolved in 5ml water injected intravenously over a period of 2½ - 5 minutes immediately prior to opening of the infarct related artery using Percutaneous Coronary Intervention
Placebo Comparator: placebo; sterile solution containing 0.9%w/v sodium chloride in 5ml water injected intravenously over a period of 2½ - 5 minutes	Other: Placebo; sterile solution containing 0.9%w/v sodium chloride in 5ml water injected intravenously over a period of 2½ - 5 minutes immediately prior to Percutaneous Coronary Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Infarct size corrected for area at risk (using ESA)	6-8 days post injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Left ventricular ejection fraction and end systolic volume index	6-8 days and 6 months post injection
Plasma creatine kinase	72 hours post injection
Troponin I	72 hours post injection
Infarct size corrected for area at risk	6 months
Infarct size corrected for area at risk (using T2)	6-8 days

Collaborators and Investigators

• Sponsor: University of Aberdeen
• Collaborators: Imperial College London; Medical Research Council; Brighton and Sussex University Hospitals NHS Trust; University of Birmingham; NHS Grampian; St George's Healthcare NHS Trust
• Investigators: Study Director: Michael Frenneaux, MD, FRCP, University of Aberdeen; Principal Investigator: Juan Carlos Kaski, MD, FRCP, St George's Healthcare NHS Trust; Principal Investigator: David HildickSmith, MD, FRCP, Brighton and Sussex University Hospitals NHS Trust

Publications and helpful links

General Publications

• Siddiqi N, Bruce M, Neil CJ, Jagpal B, Maclennon G, Cotton SC, Papadopoulo SA, Bunce N, Lim P, Schwarz K, Singh S, Hildick-Smith D, Horowitz JD, Madhani M, Boon N, Kaski JC, Dawson D, Frenneaux MP. 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). J Transl Med. 2013 May 6;11:116. doi: 10.1186/1479-5876-11-116.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: July 1, 2011
• First Submitted That Met QC Criteria: July 5, 2011
• First Posted (Estimate): July 6, 2011

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: 3/030/10