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Anakinra Versus Placebo for the Treatment of Acute MyocarditIS (ARAMIS)

This study is currently recruiting participants.
Verified June 2017 by Assistance Publique - Hôpitaux de Paris
Sponsor:
ClinicalTrials.gov Identifier:
NCT03018834
First Posted: January 12, 2017
Last Update Posted: June 15, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose

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 Intervention Phase
Acute Myocarditis Drug: ANAKINRA 100 mg/daily subcutaneously Drug: Placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Number of days alive free of any myocarditis complications [ Time Frame: 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:
  • Total cost [ Time Frame: on average 14 days ]
    Total cost

  • Total Quality Adjusted Life Year (QALYs), [ Time Frame: on average 14 days ]
    measure of the perceived utility by patients of a medication (Anakinra) that corresponds to a year of life gained

  • Incremental cost effectiveness [ Time Frame: on average 14 days ]
    cost-effectiveness of ANAKINRA in the setting of acute myocarditis

  • Cost utility ratios [ Time Frame: on average 14 days ]
    Cost utility ratios

  • Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI) [ Time Frame: at 6 month ]
    Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI)

  • Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE) [ Time Frame: at 6 month ]
    Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE)

  • LVEF assessed by cardiac MRI [ Time Frame: at 1 year ]
    LVEF assessed by cardiac MRI

  • LVEF assessed by cardiac TTE [ Time Frame: at 1 year ]
    LVEF assessed by cardiac TTE

  • All cause of death rate [ Time Frame: during the 12 months follow-up ]
    All cause of death rate

  • Cardiovascular death [ Time Frame: at 12 months ]
    Cardiovascular death

  • Heart Failure [ Time Frame: at 12 months ]
    Heart Failure

  • Ventricular tachycardia [ Time Frame: during the 12 months follow-up ]
    Ventricular tachycardia

  • NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) 50% decrease of the troponin level at discharge compared to admission [ Time Frame: at Day0 ]
    NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) 50% decrease of the troponin level at discharge compared to admission

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


Estimated Enrollment: 120
Actual Study Start Date: May 30, 2017
Estimated Study Completion Date: June 15, 2021
Estimated Primary Completion Date: June 15, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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.

  Eligibility

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.


Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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%)

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, chronic inflammatory disease, tuberculosis, HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection Latex allergy
  • Pregnancy, breastfeeding
  • Contra-indication to ANAKINRA (known hypersensitivity to the active substance or to any of the excipients,
  • neutropenia < 1,5.109/L)
  • Renal failure, Creatine Clearance (CrCl) < 30 ml/min (MDRD)
  • Asthma
  • 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
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 ClinicalTrials.gov identifier (NCT number): NCT03018834


Contacts
Contact: Mathieu KERNEIS, MD 33 142 16 29 40 mathieu.kerneis@aphp.fr
Contact: Fleur COHEN AUBART, MD 33 1 4217 82 42 fleur.cohen@aphp.fr

Locations
France
ACTION Study Group - Department of Cardiology - Pitié Salpétrière Hospital, 47 Bd de l'Hopital Recruiting
Paris, France, 75013
Contact: Mathieu KERNEIS, MD    33 1 42 16 29 40    mathieu.kerneis@aphp.fr   
Department of internal medicine - Pitié Salpétrière Hospital, 47 Bd de l'Hopital Not yet recruiting
Paris, France, 75013
Contact: Fleur COHEN AUBART, MD    33 1 42 17 82 42    fleur.cohen@aphp.fr   
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
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03018834     History of Changes
Other Study ID Numbers: P150921
2016-003433-20 ( EudraCT Number )
First Submitted: December 12, 2016
First Posted: January 12, 2017
Last Update Posted: June 15, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
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:
Acute Myocarditis
ANAKINRA

Additional relevant MeSH terms:
Myocarditis
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Adrenergic beta-Antagonists
Interleukin 1 Receptor Antagonist Protein
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antirheumatic Agents