COLCHICINE for Acute myocarditis

Inclusion criteria

• {"criterion_text":"-\tAge ≥ 18 years and < 65 years,\n-\tWritten informed consent of the patient obtained.\n-\tSymptom onset ≤ 28 days,\n-\tMyocarditis initially presenting with chest pain and/or heart failure symptoms and/or palpitations\n-\tTroponins > 99 percentile of reference value at any time between admission and inclusion,\n-\tMyocarditis diagnostic confirmed by CMR according to the Lake Louise criteria (2009 or later),\n-\tNo evidence for ischemic heart disease as assessed by coronary angiography or coronary computed tomography angiography for patients with age > 40-year-old with one or more cardiovascular risk factor (hypertension, smoking, hypercholesterolemia, diabetes, personal or family history of coronary artery disease)\n-\tWoman of child-bearing age with an effective contraception method according to the investigator for the duration of treatment and 1 month after\n-\tMan accepting effective contraception for the duration of treatment and 1 month after\n-\tPatients with affiliation to the French Health Care System “sécurité sociale”"}

Exclusion criteria

• {"criterion_text":"-\tCardiogenic shock requiring inotropes or vasopressors (patients with inotropes or vasopressors discontinued for >24h can be enrolled)\n-\tAdministration of any investigational drug or participation in another interventional trial, within 30 days before randomization.\n-\tPatient under treatment having an interaction with colchicine [macrolides (telithromycin, azithromycin, clarithromycin, dirithromycin, erythromycin, josamycin, midecamycin, roxithromycin), pristinamycin, cyclosporine, verapamil, all protease inhibitors, telaprevir, CYP3A4 powerful inhibitors, azole antifungals, vitamin K antagonists],\n-\tGiant cell myocarditis or eosinophilic myocarditis\n-\tPatients under legal protection: under guardianship (trusteeship or curatorship),\n-\tAcute coronary syndrome or known coronary stenosis > 50%\n-\tToxic cardiomyopathy\n-\tActive chronic inflammatory disease, chronic active infection, evolving cancer\n-\tA recent severe sepsis (7 days)\n-\tHypersensitivity to IMP’s active substances (colchicine) or to any of the excipients (including lactose, sucrose, microcrystalline cellulose, colloidal silica, magnesium stearate colorants: E127, Dual Red 40)\n-\tAny known contra-indication to CMR or associated contract products (claustrophobia, intra-ocular metal foreign bodies, clips such as cerebral, carotid, or aortic aneurysm, cochlear implants, any implant held in by magnet,history of hypersensitivity to gadoteric acid or to gadolinium contrast agents or to meglumine)\n-\tSarcoidosis\n-\tChronic treatment with corticosteroids or NSAIDs or high-dose aspirin or immunosuppressant.\n-\tPatients with an implantable cardioverter-defibrillator (ICD) or pacemaker (PM) are also excluded due to the risk of imaging artifacts, which may compromise the reliable quantification of late gadolinium enhancement (LGE),\n-\tSevere liver (Child Pugh C) or known renal dysfunction (known GFR < 30 ml/min according Cockroft),\n-\tCytopenia: hemoglobin less than 100 grams/L, white blood cell count less than 3.0 G/L, platelet count less than 100 G/L between admission and inclusion (within 7 days)\n-\tMajor digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)\n-\tImmunosuppression, spinal cord aplasia\n-\tHemopathy\n-\tHypereosinophilia > 0.5 G/L between admission and inclusion\n-\tPregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive local laboratory test"}

Primary endpoints

• {"endpoint_text":"- Extent of late gadolinium enhancement (% of left ventricle mass) evaluated on CMR at 6 months.","definition_or_measurement_approach":"Extent of late gadolinium enhancement measured as % of left ventricular mass on cardiac magnetic resonance (CMR) at 6 months."}
• {"endpoint_text":"- Composite clinical outcome at 6 months, defined as the occurrence of heart Failure or acute myocarditis recurrence; or a clinically relevant chest pain (defined as leading to an unplanned/urgent consultation or hospitalization or requiring an additional treatment); or a sustained ventricular arrhythmia; left ventricular assistance; or heart transplantation; or cardiovascular death during the s","definition_or_measurement_approach":"Composite clinical outcome at 6 months defined as occurrence of heart failure or acute myocarditis recurrence; clinically relevant chest pain (leading to unplanned/urgent consultation or hospitalization or requiring additional treatment); sustained ventricular arrhythmia; left ventricular assistance; heart transplantation; or cardiovascular death (as described in the primary endpoint text)."}

Secondary endpoints

• {"endpoint_text":"- Rate of Serious Adverse Events related to colchicine at 6 months, rate of permanent discontinuation on 6 months, rate of diarrhea, rate of nausea and/or vomiting and rate of myelotoxicity on 6 months, renal function during hospitalization and at 6 months.","definition_or_measurement_approach":"Safety endpoints measured as rates at 6 months: SAEs related to colchicine, permanent discontinuation rate at 6 months, rates of diarrhea, nausea/vomiting, myelotoxicity; renal function assessed during hospitalization and at 6 months."}
• {"endpoint_text":"- Efficacy of colchicine between the two groups : a- Composite clinical outcome at 1 year b- Each component of the composite clinical endpoint at 6 months and 1 year","definition_or_measurement_approach":"Efficacy measured by composite clinical outcome at 1 year and by each component of the composite at 6 months and 1 year (components defined as in primary endpoint)."}
• {"endpoint_text":"- Rate of heart failure or recurrence of acute myocarditis","definition_or_measurement_approach":"Rate of heart failure or recurrence of acute myocarditis measured during follow-up (timepoints include 6 months and 1 year as specified elsewhere)."}
• {"endpoint_text":"- Rates of clinically relevant chest pain (defined as requiring unscheduled/urgent consultation or hospitalisation or additional treatment)","definition_or_measurement_approach":"Rates of clinically relevant chest pain defined as events requiring unscheduled/urgent consultation, hospitalisation, or additional treatment."}
• {"endpoint_text":"- Rate of sustained ventricular arrhythmias","definition_or_measurement_approach":"Rate of sustained ventricular arrhythmias measured during follow-up."}
• {"endpoint_text":"- Rate of left ventricular assistance","definition_or_measurement_approach":"Rate of requirement for left ventricular assist device during follow-up."}
• {"endpoint_text":"- Rate of heart transplantation","definition_or_measurement_approach":"Rate of heart transplantation during follow-up."}
• {"endpoint_text":"- Cardiovascular mortality rate","definition_or_measurement_approach":"Cardiovascular mortality rate assessed during follow-up."}
• {"endpoint_text":"- LVEF (Left Ventricular Ejection Fraction), GEDV (TeleDiastolic Volume) and TSV (TeleSystolic Volume) volumes determined on a 6-month cardiac MRI using Corelab centralised reading.","definition_or_measurement_approach":"LVEF, end-diastolic and end-systolic volumes determined by 6-month cardiac MRI with centralised Corelab reading."}
• {"endpoint_text":"- Relative change in LVEF, LVOT and STV volumes, determined by follow-up transthoracic echocardiography at 6 months,","definition_or_measurement_approach":"Relative change in LVEF, LV volumes measured by transthoracic echocardiography at 6 months."}
• {"endpoint_text":"- The relative change in late gadolinium enhancement and oedema determined on a 6-month follow-up cardiac MRI scan using Corelab centralised reading.","definition_or_measurement_approach":"Relative change in late gadolinium enhancement and oedema measured on 6-month follow-up CMR with centralised Corelab reading."}
• {"endpoint_text":"- Cardiac magnetic resonance criteria at 6 months: value of native T1 and T2 mapping (ms), percentage of extracellular volume.","definition_or_measurement_approach":"Native T1 and T2 mapping values (ms) and percentage extracellular volume measured by cardiac MRI at 6 months."}
• {"endpoint_text":"- g/ Serum biomarkers during the hospitalization period (eg: admission, 24h, 48h (after admission), inclusion or discharge) and at 6 months: Troponin (I or T according to investigator), NT-pro BNP, CRP, CK","definition_or_measurement_approach":"Serum biomarkers (Troponin I/T, NT-proBNP, CRP, CK) measured at specified hospitalization timepoints (admission, 24h, 48h, inclusion/discharge) and at 6 months."}
• {"endpoint_text":"- For centres participating in the bio-collection: specific inflammatory markers IL-6, ST2 and IL-1β at inclusion; 24 and 48 hours after inclusion if possible; and at 6 months (after randomisation","definition_or_measurement_approach":"Specific inflammatory markers (IL-6, ST2, IL-1β) measured at inclusion, 24h, 48h if possible, and at 6 months for participating biocollection centers."}
• {"endpoint_text":"- Burden of VSE (Ventricular ExtraSystoles) measured at 3 months on Holter ECG","definition_or_measurement_approach":"Burden of ventricular extrasystoles measured at 3 months using Holter ECG."}

France

Earliest CTIS Part Ii Submission Date

02-10-2024

Latest Decision Or Authorization Date

03-03-2026

Processing Time Days

517

Number Of Sites

29

Number Of Participants

300

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"DGOS","duties_or_roles":"Source of monetary support","organisation_type":""}