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

This study is currently recruiting participants.
Verified April 2012 by Barts & The London NHS Trust
Sponsor:
Collaborator:
Queen Mary University of London
Information provided by (Responsible Party):
Barts & The London NHS Trust
ClinicalTrials.gov Identifier:
NCT01584453
First received: April 23, 2012
Last updated: April 24, 2012
Last verified: April 2012
History of Changes
  Purpose

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 Intervention Phase
Myocardial Infarction
Reperfusion Injury
Myocardial Ischemia
Cardiovascular Diseases
 Drug: Sodium Nitrite
Drug: Sodium Chloride Placebo
 Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Barts & The London NHS Trust:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 80
Study Start Date: April 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01584453

Contacts
Contact: Anthony Mathur, PhD, FRCP 02089832216 a.mathur@qmul.ac.uk
Contact: Daniel Jones, MRCP, BSc 02089832213 dan.jones@bartshealth.nhs.uk

Locations
United Kingdom
London Chest Hospital Recruiting
Bethnal Green, London, United Kingdom, E2 9JX
Principal Investigator: Anthony Mathur, FRCP, PhD            
Sub-Investigator: Daniel Jones, MRCP, BSc            
Sub-Investigator: Amrita Ahluwalia, PhD, BSc            
Sponsors and Collaborators
Barts & The London NHS Trust
Queen Mary University of London
Investigators
Principal Investigator: Anthony Mathur, FRCP, PhD Barts and the London NHS Trust/QMUL
  More Information

No publications provided

Responsible Party: Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT01584453     History of Changes
Other Study ID Numbers: 11/LO/1500
Study First Received: April 23, 2012
Last Updated: April 24, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Cardiovascular Diseases
Myocardial Ischemia
Coronary Artery Disease
Infarction
Ischemia
Myocardial Infarction
Reperfusion Injury
Heart Diseases
 Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Necrosis
Postoperative Complications

ClinicalTrials.gov processed this record on May 23, 2013