Safety and Effectiveness of Intra-coronary Nitrite in Acute Myocardial Infarction (NITRITE-AMI)
Despite advances in the treatment of heart attacks the complications and death rates from failure of the heart to pump properly after treatment remain high. A heart attack occurs when one or more of the arteries that supply blood to the heart become blocked, causing the heart to be starved of oxygen and nutrients. This results in damage to the heart and so the the heart pumps less well. The main treatment for a heart attack is balloon treatment to open the blocked artery (called primary angioplasty). Whilst re-opening the artery is essential and allows blood to flow to the area of the heart starved of oxygen, this process also causes damage itself (called reperfusion injury) and increases the size of the heart attack further. Currently there are no treatments available that reduce this reperfusion injury. The investigators and others have shown that a substance called sodium nitrite reduces reperfusion injury in experimental models of a heart attack. The aim of this research is to perform a trial to investigate whether during a heart attack, an infusion of sodium nitrite into the damaged artery protects against reperfusion injury and reduces heart attack size in patients.
Drug: Sodium Nitrite
Drug: Sodium Chloride Placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomised, Double-blind, Placebo-controlled Trial Assessing the Safety and Efficacy of Intracoronary Nitrite Infusion During Acute Myocardial Infarction|
- Infarct size measured by CK area under the curve [ Time Frame: 1st 48 hours after AMI ] [ Designated as safety issue: No ]AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours)
- Infarct size measured by Troponin T Area under the curve [ Time Frame: 1st 48 hours post AMI ] [ Designated as safety issue: No ]AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours)
- Infarct size, assessed by CMR at 6 months ± 2 weeks. [ Time Frame: 6 months ± 2 weeks. ] [ Designated as safety issue: No ]
- Infarct size as a proportion of area at risk measured at 48 hours by CMR. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
- The acute safety and tolerability of intra-coronary nitrite in STEMI [ Time Frame: 1st 48 hours ] [ Designated as safety issue: Yes ]
- Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Markers of inflammation measured at baseline, 30 minutes, 4 and 24 hours post PCI [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
- Assessment of platelet reactivity at baseline, 30 minutes, 4 and 24 hours post PCI [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
- Plasma nitrite and cyclic guanosine monophosphatase (cGMP) concentrations measured at baseline, post procedure, at 4 hours and 24 hours post-PCI [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||November 2015|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
|Experimental: Sodium Nitrite||
Drug: Sodium Nitrite
A bolus of sodium nitrite solution (1.8 micromol in 10 ml PRe-diluted in 0.9% sodium chloride in a syringe) will be delivered over 30-60 seconds via intracoronary injection initiated during the re-establishment of antegrade epicardial flow with PPCI.
|Placebo Comparator: Placebo||
Drug: Sodium Chloride Placebo
The control intervention is a bolus of 0.9% sodium chloride solution (prepared with an identical appearance to the sodium nitrite).
Coronary heart disease is still the commonest cause of death in the UK (in the main as a consequence of acute myocardial infarction (AMI)). 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 the clinical outcomes in such patients. However, substantial mortality and morbidity rates still persist with respect to longer term outcome. One of the main determinants of prognosis after AMI is the size of the infarct. Thus, identification of additional strategies that might decrease infarct size is desirable.
Evidence from pre-clinical studies suggests that inorganic nitrite administration reduces infarct size in animal models of AMI. In this study we aim to translate these findings into man. We will test the hypothesis that in patients with STEMI undergoing PPCI, an intra-coronary injection of nitrite, initiated prior to establishment of full reperfusion reduces infarct size through prevention of ischemia-reperfusion injury.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01584453
|London Chest Hospital|
|Bethnal Green, London, United Kingdom, E2 9JX|
|Principal Investigator:||Anthony Mathur, FRCP, PhD||Barts and the London NHS Trust/QMUL|