Clinical trial NCT01388504: Nitrites in Acute Myocardial Infarction
Official title: Does Sodium Nitrite Administration Reduce Ischaemia-reperfusion Injury in Patients Presenting With Acute ST Segment Elevation Myocardial Infarction?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute ST Elevation Myocardial Infarction
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
Collaborators: name: NHS Grampian
name: Medical Research Council
name: St George's Healthcare NHS Trust
name: Brighton and Sussex University Hospitals NHS Trust
name: Imperial College London
name: University of Birmingham
First posted: 2011-07-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)?"

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Infarct size corrected for area at risk (using ESA)
timeFrame: 6-8 days post injection
Secondary outcomes:
measure: Left ventricular ejection fraction and end systolic volume index
timeFrame: 6-8 days and 6 months post injection
measure: Plasma creatine kinase
timeFrame: 72 hours post injection
measure: Troponin I
timeFrame: 72 hours post injection
measure: Infarct size corrected for area at risk
timeFrame: 6 months
measure: Infarct size corrected for area at risk (using T2)
timeFrame: 6-8 days
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: St George's Healthcare NHS Trust
Study officials:
affiliation: University of Aberdeen
name: Michael Frenneaux, MD, FRCP
role: STUDY_DIRECTOR
affiliation: St George's Healthcare NHS Trust
name: Juan Carlos Kaski, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Brighton and Sussex University Hospitals NHS Trust
name: David HildickSmith, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.