Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Queen Mary University of London | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Nitrite | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Nitrite | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Infarct size measured by CK area under the curve | AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours) | 1st 48 hours after AMI |
| Measure | Description | Time Frame |
|---|---|---|
| Infarct size measured by Troponin T Area under the curve | AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours) | 1st 48 hours post AMI |
| Infarct size, assessed by CMR at 6 months ± 2 weeks. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Anthony Mathur, FRCP, PhD | Barts and the London NHS Trust/QMUL | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| London Chest Hospital | Bethnal Green | London | E2 9JX | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27683405 | Derived | Jones DA, Khambata RS, Andiapen M, Rathod KS, Mathur A, Ahluwalia A. Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention. Heart. 2017 Apr;103(7):508-516. doi: 10.1136/heartjnl-2016-309748. Epub 2016 Sep 28. | |
| 25512434 | Derived | Jones DA, Pellaton C, Velmurugan S, Rathod KS, Andiapen M, Antoniou S, van Eijl S, Webb AJ, Westwood MA, Parmar MK, Mathur A, Ahluwalia A. Randomized phase 2 trial of intracoronary nitrite during acute myocardial infarction. Circ Res. 2015 Jan 30;116(3):437-47. doi: 10.1161/CIRCRESAHA.116.305082. Epub 2014 Dec 15. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D015427 | Reperfusion Injury |
| D017202 | Myocardial Ischemia |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
Not provided
Not provided
| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| ID | Term |
|---|---|
| D009573 | Nitrites |
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Sodium Chloride Placebo | Drug | The control intervention is a bolus of 0.9% sodium chloride solution (prepared with an identical appearance to the sodium nitrite). |
|
Infarct size, assessed by CMR at 6 months ± 2 weeks.
| 6 months ± 2 weeks. |
| Infarct size as a proportion of area at risk measured at 48 hours by CMR. | Infarct size as a proportion of area at risk measured at 48 hours by CMR. | 48 hours |
| The acute safety and tolerability of intra-coronary nitrite in STEMI | Safety profile of IC nitrate (death, MI, CVA, arrhythmia, hypotension, methaemoglobinaemia) | 1st 48 hours |
| Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation) | 12 months |
| Markers of inflammation measured at baseline, 30 minutes, 4 and 24 hours post PCI | hs-CRP, MCP-1 | 24 hours |
| Assessment of platelet reactivity at baseline, 30 minutes, 4 and 24 hours post PCI | ADP, collagen, PBS | 24 hours |
| Plasma nitrite and cyclic guanosine monophosphatase (cGMP) concentrations measured at baseline, post procedure, at 4 hours and 24 hours post-PCI | 24 hours |
| Cost-utility of Nitrite over at 3 years | ICER based on outcome and QoL (EQ5D) | 3 years |
| 23550096 | Derived | Jones DA, Andiapen M, Van-Eijl TJ, Webb AJ, Antoniou S, Schilling RJ, Ahluwalia A, Mathur A. The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial. BMJ Open. 2013 Apr 2;3(4):e002813. doi: 10.1136/bmjopen-2013-002813. Print 2013. |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D011183 | Postoperative Complications |
| D017670 |
| Sodium Compounds |