Clinical Trial: Anakinra Versus Placebo for the Treatment of Acute MyocarditIS

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

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).

Detailed Summary:

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.

Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Number of days alive free of any myocarditis complications [ Time Frame: within 28 days post hospitalization ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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)

Original Secondary Outcome:

• Total cost [ Time Frame: on average 14 days ]
• 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 ]
• Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI) [ Time Frame: at 6 month ]
• Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE) [ Time Frame: at 6 month ]
• LVEF assessed by cardiac MRI [ Time Frame: at 1 year ]
• LVEF assessed by cardiac TTE [ Time Frame: at 1 year ]
• All cause of death rate [ Time Frame: during the 12 months follow-up ]
• Cardiovascular death [ Time Frame: at 12 months ]
• Heart Failure [ Time Frame: at 12 months ]
• Ventricular tachycardia [ Time Frame: during the 12 months follow-up ]
• 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 [ Time Frame: an average of 14 days ]

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: December 12, 2016
Date Started: May 15, 2017
Date Completion: June 15, 2021
Last Updated: May 14, 2017
Last Verified: May 2017