Safety and Effectiveness of Intra-coronary Nitrite in Acute Myocardial Infarction (NITRITE-AMI)
|ClinicalTrials.gov Identifier: NCT01584453|
Recruitment Status : Completed
First Posted : April 25, 2012
Last Update Posted : November 29, 2017
|Condition or disease||Intervention/treatment||Phase|
|Myocardial Infarction Reperfusion Injury Myocardial Ischemia Cardiovascular Diseases||Drug: Sodium Nitrite Drug: Sodium Chloride Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomised, Double-blind, Placebo-controlled Trial Assessing the Safety and Efficacy of Intracoronary Nitrite Infusion During Acute Myocardial Infarction|
|Actual Study Start Date :||April 2012|
|Actual Primary Completion Date :||November 2013|
|Actual Study Completion Date :||January 2016|
|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).
- Infarct size measured by CK area under the curve [ Time Frame: 1st 48 hours after AMI ]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 ]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. ]Infarct size, assessed by CMR at 6 months ± 2 weeks.
- Infarct size as a proportion of area at risk measured at 48 hours by CMR. [ Time Frame: 48 hours ]Infarct size as a proportion of area at risk measured at 48 hours by CMR.
- The acute safety and tolerability of intra-coronary nitrite in STEMI [ Time Frame: 1st 48 hours ]Safety profile of IC nitrate (death, MI, CVA, arrhythmia, hypotension, methaemoglobinaemia)
- Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation) [ Time Frame: 12 months ]
- Markers of inflammation measured at baseline, 30 minutes, 4 and 24 hours post PCI [ Time Frame: 24 hours ]hs-CRP, MCP-1
- Assessment of platelet reactivity at baseline, 30 minutes, 4 and 24 hours post PCI [ Time Frame: 24 hours ]ADP, collagen, PBS
- 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 ]
- Cost-utility of Nitrite over at 3 years [ Time Frame: 3 years ]ICER based on outcome and QoL (EQ5D)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01584453
|London Chest Hospital|
|Bethnal Green, London, United Kingdom, E2 9JX|
|Principal Investigator:||Anthony Mathur, FRCP, PhD||Barts and the London NHS Trust/QMUL|