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    Summary
    EudraCT Number:2011-000721-77
    Sponsor's Protocol Code Number:NITRITE/AMI/4.1
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-10-21
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2011-000721-77
    A.3Full title of the trial
    A randomised, double-blind, placebo-controlled trial assessing the safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial investigating the use of sodium nitrite in the immediate treatment of heart attacks
    A.3.2Name or abbreviated title of the trial where available
    NITRITE-AMI
    A.4.1Sponsor's protocol code numberNITRITE/AMI/4.1
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01584453
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBarts Health NHS Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNational Institute of Health Research (NIHR): Clinical Research Fellowship
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBarts and the London NHS Trust
    B.5.2Functional name of contact pointProfessor Anthony Mathur
    B.5.3 Address:
    B.5.3.1Street AddressDepartment of Cardiology
    B.5.3.2Town/ cityLondon Chest Hospital
    B.5.3.3Post codee2 9JX
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number020 8983 2216
    B.5.5Fax number020 8983 2381
    B.5.6E-maila.mathur@qmul.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSodium Nitrite (435micromol/ml) in water for injection
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntracoronary use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSodium Nitrite 3% w/v (435umol/ml)
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/V) percent weight/volume
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.7% to 3.3%
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntracoronary use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Acute myocardial Infarction
    E.1.1.1Medical condition in easily understood language
    Heart Attack
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 15.1
    E.1.2Level PT
    E.1.2Classification code 10028596
    E.1.2Term Myocardial infarction
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine whether the intracoronary delivery of nitrite in patients undergoing primary percutaneous coronary angioplasty (PPCI) for acute myocardial infarction (heart attack) decreases the amount of damage caused by the heart attack (as measured by levels of damage detected in blood tests)
    E.2.2Secondary objectives of the trial
    Aims

    1. To demonstrate that the intracoronary delivery of nitrite is safe
    2. To show that nitrite reduces heart attack (myocardial infarct) size as assessed by enzyme biomarkers
    3. To demonstrate the effects of nitrite on left ventricular dimensions and function as assessed by cardiovascular magnetic resonance (CMR)
    4. To identify the mechanisms by which nitrite decreases infarct size.
    5. To show that over a 1 year follow-up nitrite decreases the rate of major adverse cardiac events (MACE)(including death, repeat heart attack, repeat unplanned balloon angioplasty and stent insertion, stroke).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1). Patients aged between 18 and 80 years
    2). Acute ST-elevation myocardial infarction with ECG showing at least 2 mm of ST
    segment elevation in 2 or more limb leads or 1mm in 2 or more contiguous chest
    leads, or new left bundle branch block
    3). Haemodynamically stable
    4). Estimated symptom to balloon or aspiration time < 6 hours
    5). A signed and dated written informed consent prior to admission to the study
    6). Angiographicallly
    i). PPCI indicated for revascularisation
    ii). Single epicardial artery to be treated
    iii). Expected ability to use the over the wire balloon for delivery of nitrite
    E.4Principal exclusion criteria
    1). Inability to consent (e.g. language)
    2). Patients already on nitrate Treatment (Nicorandil, ISMN)
    3). Previous history of myocardial infarction (MI) or systolic dysfunction
    4). Previous coronary artery bypass surgery (CABG)
    5). Subjects presenting with cardiogenic shock (SBP <80 mmHg for >30 minutes, or
    requiring inotropes or emergency Intra-Aortic Balloon Pump (IABP) for
    hypotension treatment) or cardiopulmonary resuscitation
    6). Current diagnosis of or treatment for malignancy, other than non-melanoma skin
    cancer.
    7). Current life-threatening condition other than vascular disease that may prevent
    a subject completing the study.
    8). 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.
    9). 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).
    10). Severe acute infection, or significant trauma (burns, fractures).
    11). Pregnancy.
    12). Contra-indications to CMR scanning
    i). Pacemakers, intracranial clips or other metal implants or foreign
    bodies,
    ii). claustrophobia
    iii). Renal Failure (eGFR<30mls/min)
    13). History of alcohol or drug abuse within the past 6 months.
    14). History of congenital methaemoglobinaemia.
    15). Angiographically
    i). Severe vessel tortuosity, diffuse disease or severe calcification is
    present which may impede successful delivery of the over the wire balloon
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint for the study is infarct size, measured by area under the creatine kinase curve over 48 hours. Blood samples will be taken at baseline, 4, 8, 12, 18, 24, 36, and 48 hours post Primary PCI. Area under the curve of serum creatine kinase release will be measured in each patient by computerized planimetry and used as measure of infarct size.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Blood samples will be taken at baseline, 4, 8, 12, 18, 24, 36, and 48 hours post Primary PCI.
    E.5.2Secondary end point(s)
    a) Infarct size, assessed by troponin T area under the curve (AUC) over 48
    hours
    b) Infarct size, assessed by CMR at 6 months ± 2 weeks.
    c) Infarct size as a proportion of area at risk measured at 48 hours by CMR.
    d) Microvascular obstruction measured on early post-gadolinium imaging at 48 hours by CMR
    e) Difference in left ventricular ejection fraction (LVEF), Left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by CMR at 6 months ± 2 weeks.
    f) Presence of myocardial haemorrhage on CMR at 48 hours and 6 months
    g) Plasma nitrite and cyclic guanosine monophosphatase (cGMP) concentrations measured at baseline, post procedure, at 8 hours, 24 hours and 48 hours post-PCI
    h) Markers of inflammation measured at baseline, 8 hours,
    24 hours and 48 hours post PCI
    i) Assessment of platelet reactivity at baseline, during procedure, 8 and 24
    hours post PCI
    i) To demonstrate acute safety and tolerability of intra-coronary nitrite in STEMI; haemodynamic effects and major adverse events within the first 48 hours (death, heart failure, myocardial infarction, stroke, recurrent ischaemia or revascularisation, renal/hepatic damage, vascular complications, bleeding).
    j) Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Troponin T at baseline, 4, 8, 12, 18, 24, 36, and 48 hours post Primary PCI
    CMR at day 2 and 6 months
    Markers of inflammation/platelet activity and nitrite at baseline, 8, and 24 hours
    MACE follow-up at 1 year
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The study will end when all patients recruited have completed their 3rd annual telephone call follow-up
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days28
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state80
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients will be followed up as part of their standard care by their GP or Consultant Cardiologist. They will be telephoned yearly for 3 years by the research department, however due to the nature of the intervention (one-off bolus during the acute setting) continued provision of the therapy is not applicable.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-12-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-11-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-09-29
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