Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003433-20 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A: ANAKINRA | Experimental | 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. |
|
| B: Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ANAKINRA 100 mg/daily subcutaneously | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Total cost | Total cost | on average 14 days |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mathieu KERNEIS, MD | ACTION Study Group - Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Fleur COHEN AUBART, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Gilles MONTALESCOT, MD, PhD | ACTION Study Group - Assistance Publique - Hôpitaux de Paris | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ACTION Study Group - Department of Cardiology - Pitié Salpétrière Hospital, 47 Bd de l'Hopital | Paris | 75013 | France | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39705605 | Derived | Werner B, Roznowska-Wojtowicz A, Puchalski M. Diagnosis and Management of Pediatric Myocarditis. Pediatr Infect Dis J. 2025 Mar 1;44(3):e95-e98. doi: 10.1097/INF.0000000000004678. Epub 2024 Dec 17. No abstract available. | |
| 37640625 | Derived | Kerneis M, Cohen F, Combes A, Amoura Z, Pare C, Brugier D, Puymirat E, Abtan J, Lattuca B, Dillinger JG, Hauguel-Moreau M, Silvain J, Salem JE, Gandjbakhch E, Hekimian G, Redheuil A, Vicaut E, Montalescot G; ACTION Study Group. Rationale and design of the ARAMIS trial: Anakinra versus placebo, a double blind randomized controlled trial for the treatment of acute myocarditis. Arch Cardiovasc Dis. 2023 Oct;116(10):460-466. doi: 10.1016/j.acvd.2023.07.004. Epub 2023 Aug 12. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D053590 | Interleukin 1 Receptor Antagonist Protein |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | 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. |
|
| on average 14 days |
| Incremental cost effectiveness | cost-effectiveness of ANAKINRA in the setting of acute myocarditis | on average 14 days |
| Cost utility ratios | Cost utility ratios | on average 14 days |
| 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 |
| 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 |
| LVEF assessed by cardiac MRI | LVEF assessed by cardiac MRI | at 1 year |
| LVEF assessed by cardiac TTE | LVEF assessed by cardiac TTE | at 1 year |
| All cause of death rate | All cause of death rate | during the 12 months follow-up |
| Cardiovascular death | Cardiovascular death | at 12 months |
| Heart Failure | Heart Failure | at 12 months |
| Ventricular tachycardia | Ventricular tachycardia | 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) 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 |
| 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 |
| Department of internal medicine - Pitié Salpétrière Hospital, 47 Bd de l'Hopital |
| Paris |
| 75013 |
| France |
| D011506 | Proteins |
| D001685 | Biological Factors |