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Safety and Effectiveness of Intra-coronary Nitrite in Acute Myocardial Infarction (NITRITE-AMI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01584453
Recruitment Status : Completed
First Posted : April 25, 2012
Last Update Posted : November 29, 2017
Queen Mary University of London
Information provided by (Responsible Party):
Barts & The London NHS Trust

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myocardial Infarction Reperfusion Injury Myocardial Ischemia Cardiovascular Diseases Drug: Sodium Nitrite Drug: Sodium Chloride Placebo Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : April 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
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).

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. 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)

  2. 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.

  3. 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.

  4. 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)

  5. Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation) [ Time Frame: 12 months ]
  6. Markers of inflammation measured at baseline, 30 minutes, 4 and 24 hours post PCI [ Time Frame: 24 hours ]
    hs-CRP, MCP-1

  7. Assessment of platelet reactivity at baseline, 30 minutes, 4 and 24 hours post PCI [ Time Frame: 24 hours ]
    ADP, collagen, PBS

  8. 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 ]
  9. Cost-utility of Nitrite over at 3 years [ Time Frame: 3 years ]
    ICER based on outcome and QoL (EQ5D)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients aged at least 18 years
  • Acute STEMI with ECG showing ST-segment elevation of 1mm or more in two adjacent limb leads or 2mm or more in at least two contiguous precordial leads or new left bundle branch block;
  • Haemodynamically stable
  • Estimated symptom to balloon or aspiration time < 6 hours
  • Angiographically i) PPCI indicated for revascularisation ii) Single epicardial artery to be treated iii) Expected ability to use over the wire balloon

Exclusion Criteria:

  • Patients on organic nitrate treatment (Nicorandil, isosorbide mononitrate)
  • Previous history of AMI, systolic dysfunction or CABG
  • Subjects presenting with cardiogenic shock (systolic blood pressure <80 mmHg for > 30 minutes, or requiring inotropes/emergency intra aortic balloon pump or cardiopulmonary resuscitation
  • Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
  • Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
  • Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
  • Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject's unwillingness to comply with all study-related procedures).
  • Severe acute infection, or significant trauma (burns, fractures).
  • Pregnancy.
  • Contra-indications to CMR scanning i) Pacemakers, intracranial clips or other metal implants ii) Claustrophobia iii) Renal failure (eGFR < 30mls/min)
  • History of alcohol or drug abuse within the past 6 months.
  • History of congenital methaemoglobinaemia.
  • Angiographically severe vessel tortuosity, diffuse disease or severe calcification which may impede successful delivery of the the over the wire balloon.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01584453

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United Kingdom
London Chest Hospital
Bethnal Green, London, United Kingdom, E2 9JX
Sponsors and Collaborators
Barts & The London NHS Trust
Queen Mary University of London
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Principal Investigator: Anthony Mathur, FRCP, PhD Barts and the London NHS Trust/QMUL

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Barts & The London NHS Trust Identifier: NCT01584453    
Other Study ID Numbers: 11/LO/1500
First Posted: April 25, 2012    Key Record Dates
Last Update Posted: November 29, 2017
Last Verified: July 2015
Additional relevant MeSH terms:
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Myocardial Infarction
Myocardial Ischemia
Reperfusion Injury
Cardiovascular Diseases
Pathologic Processes
Heart Diseases
Vascular Diseases
Postoperative Complications