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

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3; Phase 2

Conditions: Acute Myocarditis

Treatments: Drug: Placebo; Drug: ANAKINRA 100 mg/daily subcutaneously

Study type: Interventional

Funder types: Other

Identifiers

NCT03018834

P150921

2016-003433-20 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 120 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 2 patient groups, including a placebo group

A: ANAKINRA

Experimental group

Description:

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.

Treatment:

Drug: ANAKINRA 100 mg/daily subcutaneously

B: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo