Anakinra Versus Placebo for the Treatment of Acute MyocarditIS

Acute Myocarditis Clinical Trial

— ARAMIS  

Official title:

Anakinra Versus Placebo Double Blind Randomized Controlled Trial for the Treatment of Acute MyocarditIS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03018834
• Other study ID #: P150921
• Secondary ID: 2016-003433-20
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 30, 2017
• Est. completion date: May 30, 2022

Study information

• Verified date: March 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 30, 2022
• Est. primary completion date: June 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myocarditis
• Myocarditis

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	ACTION Study Group - Department of Cardiology - Pitié Salpétrière Hospital, 47 Bd de l'Hopital	Paris
France	Department of internal medicine - Pitié Salpétrière Hospital, 47 Bd de l'Hopital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of days alive free of any myocarditis complications	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	within 28 days post hospitalization
Secondary	Total cost	Total cost	on average 14 days
Secondary	Total Quality Adjusted Life Year (QALYs),	measure of the perceived utility by patients of a medication (Anakinra) that corresponds to a year of life gained	on average 14 days
Secondary	Incremental cost effectiveness	cost-effectiveness of ANAKINRA in the setting of acute myocarditis	on average 14 days
Secondary	Cost utility ratios	Cost utility ratios	on average 14 days
Secondary	Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI)	Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI)	at 6 month
Secondary	Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE)	Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE)	at 6 month
Secondary	LVEF assessed by cardiac MRI	LVEF assessed by cardiac MRI	at 1 year
Secondary	LVEF assessed by cardiac TTE	LVEF assessed by cardiac TTE	at 1 year
Secondary	All cause of death rate	All cause of death rate	during the 12 months follow-up
Secondary	Cardiovascular death	Cardiovascular death	at 12 months
Secondary	Heart Failure	Heart Failure	at 12 months
Secondary	Ventricular tachycardia	Ventricular tachycardia	during the 12 months follow-up
Secondary	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	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
Secondary	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	NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or BNP = 400pg/mL	an average of 14 days