ARAMIS: Anakinra Versus Placebo for the Treatment of Acute MyocarditIS

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03018834
Collaborator
(none)
120
Enrollment
2
Locations
2
Arms
60
Anticipated Duration (Months)
60
Patients Per Site
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is no specific treatment of acute myocarditis, especially during the inflammatory period. Interleukin (IL) is specifically involved during this period and play a role in myocardial oedema. ANAKINRA, an IL-1β Blocker, is a new treatment that has never been evaluated in myocarditis. The benefit for the patient could be important with a reduction of heart failure and ventricular arrhythmias.

Hypothesis : ANAKINRA in addition to standard therapy for treatment of Acute Myocarditis is superior to standard therapy based on an association of beta-blockers and Angiotensin-Converting-Enzyme inhibitor (ACE).

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: ANAKINRA 100 mg/daily subcutaneously
  • Drug: Placebo
Phase 2/Phase 3

Detailed Description

It is a Double Blind Randomized clinical trial Phase IIb of superiority, enrolling two groups: one group treated with the standard of care, defined as the maximum tolerated dosage of any beta blockers and ACE, and placebo versus ANAKINRA in addition to the standard of care in patients treated for an acute Myocarditis.

Patients will be randomized to receive ANAKINRA 100 mg/daily or placebo subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months. Randomization 1:1 will be conducted centrally using the electronic Case Report Form (eCRF).

As an exploratory analysis, a second randomization for ACE discontinuation in patients without left ventricular dysfunction (LVEF > 50%) at one month post discharge will be performed.

One group will stopped the treatment at one month and the second group will continued the ACE for 6 months. This second randomization is in open label.

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Anakinra Versus Placebo Double Blind Randomized Controlled Trial for the Treatment of Acute MyocarditIS
Actual Study Start Date :
May 30, 2017
Actual Primary Completion Date :
Jun 15, 2021
Anticipated Study Completion Date :
May 30, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: A: ANAKINRA

ANAKINRA 100 mg/daily subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months.

Drug: ANAKINRA 100 mg/daily subcutaneously
ANAKINRA 100 mg/daily subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months.
Other Names:
  • Kineret
  • Placebo Comparator: B: Placebo

    PLACEBO 100 mg/daily subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months.

    Drug: Placebo
    PLACEBO 100 mg/daily subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months.

    Outcome Measures

    Primary Outcome Measures

    1. Number of days alive free of any myocarditis complications [within 28 days post hospitalization]

      Number of days alive free of any myocarditis complications defined as ventricular arrhythmias, heart failure, chest pain, ventricular dysfunction defined as LVEF<50%, within 28 days post hospitalization

    Secondary Outcome Measures

    1. Total cost [on average 14 days]

      Total cost

    2. Total Quality Adjusted Life Year (QALYs), [on average 14 days]

      measure of the perceived utility by patients of a medication (Anakinra) that corresponds to a year of life gained

    3. Incremental cost effectiveness [on average 14 days]

      cost-effectiveness of ANAKINRA in the setting of acute myocarditis

    4. Cost utility ratios [on average 14 days]

      Cost utility ratios

    5. Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI) [at 6 month]

      Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI)

    6. Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE) [at 6 month]

      Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE)

    7. LVEF assessed by cardiac MRI [at 1 year]

      LVEF assessed by cardiac MRI

    8. LVEF assessed by cardiac TTE [at 1 year]

      LVEF assessed by cardiac TTE

    9. All cause of death rate [during the 12 months follow-up]

      All cause of death rate

    10. Cardiovascular death [at 12 months]

      Cardiovascular death

    11. Heart Failure [at 12 months]

      Heart Failure

    12. Ventricular tachycardia [during the 12 months follow-up]

      Ventricular tachycardia

    13. NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or BNP ≤ 400pg/mL 50% decrease of the troponin level at discharge compared to admission [at Day0]

      NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or BNP ≤ 400pg/mL 50% decrease of the troponin level at discharge compared to admission

    14. NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or BNP ≤ 400pg/mL 50% decrease of the troponin level at discharge compared to admission [an average of 14 days]

      NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or BNP ≤ 400pg/mL

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 64 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients hospitalized for Acute myocarditis defined as:

    • Chest Pain (or modification of the ECG) AND Troponin Rise (*1.5 Normal range) AND Myocarditis proven by MRI in the first 72h after admission

    • Age > 18 and <65 years old

    • Accepting effective contraception during treatment duration (men and women childbearing potential)

    • Signed informed consent Normal Coronary angiography or coronary CT Scan (made during the previous year is acceptable) (normal is defined as stenosis < 50%) (In the case of patients under 40 with typical MRI of myocarditis, coronary angiography is not mandatory and left to the doctor's discretion)

    Exclusion Criteria:
    • Active coronary disease

    • Clinical Suspicion or proven underlying disease: systemic lupus, antiphospholipid antibodies, Lyme disease, trypanosomiase disease, myositis, signs of sarcoidosis, giant cell myocarditis, treated chronic inflammatory disease, tuberculosis, HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV), Hepatitis B virus (HBV) infection,

    • Latex allergy

    • Pregnancy, breastfeeding

    • Contra-indication to ANAKINRA (known hypersensitivity to the active substance or to any of the excipients, neutropenia < 1,5.10^9/L)

    • Renal failure, Creatine Clearance (CrCl) < 30 ml/min (MDRD)

    • Malignancy or any comorbidity limiting survival or conditions predicting inability to complete the study

    • History of malignancy

    • Non Steroidian Anti Inflammatory drug within the past 14 days

    • Anti Tumor Necrosis Factor (TNF) within the past 14 days

    • No affiliation to the French Health Care System "sécurité sociale"

    • Hepatic impairment = Child-Pugh Class C

    • Mechanical ventilation

    • Circulatory assistance

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1ACTION Study Group - Department of Cardiology - Pitié Salpétrière Hospital, 47 Bd de l'HopitalParisFrance75013
    2Department of internal medicine - Pitié Salpétrière Hospital, 47 Bd de l'HopitalParisFrance75013

    Sponsors and Collaborators

    • Assistance Publique - Hôpitaux de Paris

    Investigators

    • Principal Investigator: Mathieu KERNEIS, MD, ACTION Study Group - Assistance Publique - Hôpitaux de Paris
    • Principal Investigator: Fleur COHEN AUBART, MD, Assistance Publique - Hôpitaux de Paris
    • Study Director: Gilles MONTALESCOT, MD, PhD, ACTION Study Group - Assistance Publique - Hôpitaux de Paris

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Assistance Publique - Hôpitaux de Paris
    ClinicalTrials.gov Identifier:
    NCT03018834
    Other Study ID Numbers:
    • P150921
    • 2016-003433-20
    First Posted:
    Jan 12, 2017
    Last Update Posted:
    Aug 30, 2021
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Assistance Publique - Hôpitaux de Paris
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 30, 2021