- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05855746
Colchicine Versus Placebo in Acute Myocarditis Patients (ARGO)
Colchicine Versus Placebo in Acute Myocarditis Patients to Reduce Late Gadolinium Enhancement Mass on Cardiac Magnetic Resonance and the Risk of Clinical Outcomes: The ARGO Trial
Myocarditis is an inflammatory disease of the heart, mostly caused by viruses. Patients with acute myocarditis are exposed to several complications: recurrence, ventricular arrhythmias (from 5 to 30%), heart failure (5-10%), death or heart transplantation (< 4%). To date, there is no specific treatment for myocarditis. Patient management only focuses upon empirical optimal care of arrhythmia and heart failure.
There is a strong rationale for using colchicine in acute myocarditis:
- the IL1 (Interleukin1) pathway plays a detrimental role in acute myocarditis. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome assembly, and subsequent IL-1beta production, are profoundly inhibited by colchicine.
- colchicine has been shown to improve cardiac outcomes in inflammatory cardiac disorders, including pericarditis, coronary artery disease, and post pericardiotomy syndrome.
- In murine model of CVB3-induced myocarditis (coxsackievirus B3), colchicine improved myocarditis through reduction of NLRP3 activity.
- Small case series with improvement of left ejection fraction in myocarditis following low-dose colchicine in addition to conventional heart failure therapy have been reported.
With its pleiotropic anti-inflammatory effect in the pro-inflammatory cascade, reducing the myocardial damage and cell death induced during myocarditis, colchicine has the potential to reduce the risk of heart failure and ventricular arrhythmias. Finally, colchicine is a drug widely available, at low cost, and has a long and well-known safety record.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is a prospective, randomized, multicenter, double blind, controlled versus placebo, phase III study in which two groups of participants are compared: a group treated with the experimental treatment Colchicine (in addition to standard of care therapy) compared to a control group that receive the corresponding placebo (in addition to standard of care therapy).
The inclusion visit takes place during the hospitalization stay. The study is presented to all patients presenting with acute myocarditis symptoms and inclusion criteria, hospitalized in participating centers.
Once eligible participants have been informed and signed their informed consent, they are randomized (1:1) by a centralized web system (IWRS) in the experimental group (Colchicine) or the control group (Placebo).
Participants receive then a numbered box with three months' treatment of Colchicine or placebo. The treatment must start at least within 72h after randomization. Another dispensing is performed during the three months' follow-up visit.
All randomized participants are followed during six months after the end of the treatment.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Thomas BOCHATON
- Phone Number: +33472357549
- Email: thomas.bochaton@chu-lyon.fr
Study Contact Backup
- Name: Julia CANTERINI
- Phone Number: +33427856628
- Email: julia.canterini@chu-lyon.fr
Study Locations
-
-
-
Bron, France, 69029
- Unité de Soins Intensifs Cardiologiques - Hôpital Cardiovasculaire Louis Pradel
-
Contact:
- Thomas BOCHATON
- Phone Number: +33472357549
- Email: thomas.bochaton@chu-lyon.fr
-
Contact:
- Julia CANTERINI
- Phone Number: +33427856628
- Email: julia.canterini@chu-lyon.fr
-
Paris, France, 75013
- Institut de Cardiologie - APHP Pitié Salpêtrière
-
Contact:
- Mathieu KERNEIS
- Phone Number: +33142163074
- Email: mathieu.kerneis@aphp.fr
-
Contact:
- Karine BROCHARD
- Phone Number: +3142162959
- Email: karine.brochard-ext@aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Symptom onset of 21 days or less,
- Chest pain and/or Heart failure symptoms and/or palpitations
- Troponins superior to 99 percentile of reference value,
- Myocarditis diagnostic confirmation (by Contrast-Enhanced Cardiac Magnetic Resonance (CMR), according to the Lake Louise criteria with the presence of myocardial damage),
- No evidence for ischemic heart disease on coronary angiography or coronary computed tomography angiography for patients with age superior to 40-year-old with one or more cardiovascular risk factor (hypertension, smoking, hypercholesterolemia, diabetes, personal or family history of coronary artery disease),
- Woman of child-bearing age with an effective contraception method according to the investigator for the duration of treatment and one month after,
- Man accepting effective contraception for the duration of treatment and one month after,
- Participant with affiliation to the French Health Care System "sécurité sociale",
- Written informed consent of the patient obtained.
Exclusion Criteria:
- Cardiogenic shock requiring inotropes or vasopressors (patients with inotropes discontinued for more than 24 hours can be enrolled)
- Giant cell myocarditis or eosinophilic myocarditis
- Acute coronary syndrome or known coronary stenosis superior to 50%
- Toxic cardiomyopathy
- Active chronic inflammatory disease, chronic active infection, evolving cancer
- A recent severe sepsis (7 days) or all recent acute illness
- Hypersensitivity to Investgational Medical Product's active substances (colchicine) or to any of the excipients (including lactose, sucrose, microcrystalline cellulose, colloidal silica, magnesium stearate, colourants : E127, Dual Red 40 )
- Any known contra-indication to CMR or associated contract products (claustrophobia, pace maker, defibrillator, history of hypersensitivity to gadoteric acid or to gadolinium contrast agents or to meglumine),
- Chronic treatment with corticosteroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or immunosuppressant.
- Sarcoidosis
- Severe liver (Child Pugh C) or known renal dysfunction (known Glomerular Filtration Rate (GFR) less or equal to 30 ml/min according Cockroft),
- Cytopenia : hemoglobin less than 100 grams/L, white blood cell count less than 3.0 G/L, platelet count less than 100 G/L
- Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)
- Immunosuppression, spinal cord aplasia
- Hemopathy
- Hypereosinophilia more than 0.5 G/L
- Pregnant 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,
- Administration of any investigational drug or participation in another interventional trial, within 30 days before randomization,
- Participant 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,
- Participant under legal protection: under guardianship (trusteeship or curatorship)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Colchicine
Participant receive in addition to standard of care therapy, six months of Colchicine
|
Participant receive, in addition to standard of care therapy, six months of colchicine (at a dose of 0.5 mg twice daily, morning and evening) beginning maximum 72 hours post-randomization. The standard of care is defined according to the European consensus paper as follow: All participants without contraindication receive a betablockers, and heart failure ESC (European Society of Cardiology) guidelines directed medical therapies if LVEF < 50% (Left Ventricular Ejection Fraction), including ACE (Angiotensin-Converting Enzyme) inhibitors, diuretics if indicated. The choice of the dosage and the drug is left at the investigator decision. During the six months of the treatment administration, in case of severe adverse reaction (such as nausea and/or diarrhea during five days), a dose reduction could be considered by the investigator: half of the study protocol dose could be accepted (0.5 mg per day in the morning). In case of remaining adverse reactions, the study drug should be stopped.
Other Names:
|
Placebo Comparator: Placebo
Participant receive in addition to standard of care therapy, six months of placebo
|
Participant receive, in addition to standard of care therapy, six months of placebo (at a dose of 0.5 mg twice daily, morning and evening) beginning maximum 72 hours post-randomization. The standard of care is defined according to the European consensus paper as follow: All participants without contraindication receive a betablockers, and heart failure ESC (European Society of Cardiology) guidelines directed medical therapies if LVEF < 50% (Left Ventricular Ejection Fraction), including ACE (Angiotensin-Converting Enzyme) inhibitors, diuretics if indicated. The choice of the dosage and the drug is left at the investigator decision. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Extent of Late Gadolinium Enhancement (LGE) evaluated on Cardiac Magnetic Resonance (CMR)
Time Frame: Six months post-inclusion
|
Extent of LGE (pourcentage of left ventricle mass) is evaluated (centralized reading by the Corelab) on CMR performed at six months and compared to baseline CMR (performed at the hospital admision or inclusion). The inclusion visit takes place during the initial hospitalization. |
Six months post-inclusion
|
Composite Clinical primary outcome
Time Frame: Six months post-inclusion
|
Composite Clinical primary outcome is assessed during the study period at six months on:
|
Six months post-inclusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of colchicine
Time Frame: Six months post-inclusion
|
Safety of colchicine is defined as :
|
Six months post-inclusion
|
Composite clinical secondary outcome
Time Frame: one year post-inclusion
|
Composite Clinical secondary outcome is assessed during the study period at one year on:
|
one year post-inclusion
|
Left ventricular volume on Cardiac Magnetic Resonance (CMR)
Time Frame: Six months post-inclusion
|
Left Ventricular Ejection Fraction (LVEF), left ventricular end-diastolic and left ventricular end-systolic volumes are evaluated (centralized reading by the Corelab) on CMR performed at six months and compared to baseline CMR (performed at the hospital admision or inclusion).
|
Six months post-inclusion
|
Left ventricular volume on transthoracic echocardiography (TTE)
Time Frame: 6 months post-inclusion
|
Relative variation in Left ventricular ejection fraction (LVEF), end-diastolic volume and end-systolic volume between baseline and 6-months as determined by TTE.
|
6 months post-inclusion
|
Relative variation in Extent of late gadolinium enhancement (LGE) and edema
Time Frame: Six months post-inclusion
|
Relative variation in LGE and edema between baseline and six months determined centrally by the Corelab on the CMR
|
Six months post-inclusion
|
Tissue properties evaluated on Cardiac Magnetic Resonance (CMR)
Time Frame: Six months post-inclusion
|
Cardiac magnetic resonance criteria: value of native T1 and T2 mapping (ms), pourcentage of extracellular volume
|
Six months post-inclusion
|
Serum biomarkers
Time Frame: Six months post-inclusion
|
Serum biomarkers at hospital admission, 24h and 48h (after admission) and at six months: Troponin (I or T according to investigator), N-terminal pro-brain natriuretic peptide (NT-pro BNP), C-Reactiv Protein (CRP) and Creatin Kinase (CK)
|
Six months post-inclusion
|
Specific Inflammatory markers
Time Frame: Inclusion visit and 24 hours and 48 hours post-inclusion visit
|
A biocollection, only for participating centers, is performed for specific Inflammatory markers : interleukin 6 (IL-6), interleukin 1 beta (IL-1bβ) and ST2 (or soluble interleukin 1 receptor-like 1).
Patients undergo two blood samples of 4 mL at inclusion ; 24 hours and 48 hours after the inclusion visit, if the patient is still in hospital.
|
Inclusion visit and 24 hours and 48 hours post-inclusion visit
|
Ventricular premature complex (VPC) evaluated on Holter ElectroCardiogramm (ECG)
Time Frame: three months post-inclusion
|
VPC burden on Holter ECG performed during the hopsital consultation at three months
|
three months post-inclusion
|
Collaborators and Investigators
Investigators
- Study Chair: Thomas BOCHATON, Cardiovascular hospital Louis Pradel
- Study Director: Mathieu KERNEIS, Department of Cardiology - Pitié Salpêtrière Hospital
Publications and helpful links
General Publications
- Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Ciro A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319.
- Peretto G, Sala S, Rizzo S, Palmisano A, Esposito A, De Cobelli F, Campochiaro C, De Luca G, Foppoli L, Dagna L, Thiene G, Basso C, Della Bella P. Ventricular Arrhythmias in Myocarditis: Characterization and Relationships With Myocardial Inflammation. J Am Coll Cardiol. 2020 Mar 10;75(9):1046-1057. doi: 10.1016/j.jacc.2020.01.036.
- Tschope C, Cooper LT, Torre-Amione G, Van Linthout S. Management of Myocarditis-Related Cardiomyopathy in Adults. Circ Res. 2019 May 24;124(11):1568-1583. doi: 10.1161/CIRCRESAHA.118.313578.
- Imazio M, Brucato A, Cemin R, Ferrua S, Maggiolini S, Beqaraj F, Demarie D, Forno D, Ferro S, Maestroni S, Belli R, Trinchero R, Spodick DH, Adler Y; ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013 Oct 17;369(16):1522-8. doi: 10.1056/NEJMoa1208536. Epub 2013 Aug 31.
- Kyto V, Sipila J, Rautava P. Rate and patient features associated with recurrence of acute myocarditis. Eur J Intern Med. 2014 Dec;25(10):946-50. doi: 10.1016/j.ejim.2014.11.001. Epub 2014 Nov 7.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP211429
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myocarditis
-
University Hospital, AntwerpNiguarda HospitalNot yet recruiting
-
Massachusetts General HospitalBristol-Myers SquibbRecruitingCancer | Myocarditis AcuteUnited States, Canada
-
Cardiol Therapeutics Inc.RecruitingAcute MyocarditisUnited States, Israel, Brazil, France, Canada
-
M.D. Anderson Cancer CenterCompletedMyocarditis AcuteUnited States
-
Niguarda HospitalIstituto Di Ricerche Farmacologiche Mario Negri; Ministry of Health, Italy; University... and other collaboratorsRecruitingMyocarditis AcuteItaly, United States, Spain, Belgium, Slovenia, Finland, France, Sweden, Czechia, Denmark, Germany, Greece
-
Assistance Publique - Hôpitaux de ParisCompleted
-
Samsung Medical CenterAsan Medical Center; Chonnam National University Hospital; Korea University Anam... and other collaboratorsCompletedMyocarditis AcuteKorea, Republic of
-
University Hospital, BonnCompleted
-
Cardiology Research UBCRecruitingMyocarditis | Pericarditis | Myocarditis Acute | Pericarditis AcuteCanada
-
Assistance Publique - Hôpitaux de ParisRecruitingPatients With Suspected Acute MyocarditisFrance
Clinical Trials on Colchicine Pill
-
Sohag UniversityNot yet recruitingPeriprocedural Myocardial Injury | Periprocedural Myocardial Infarction
-
Beijing Anzhen HospitalNot yet recruitingST Elevation Myocardial Infarction | Acute Coronary Syndrome | Unstable Angina | Non ST Segment Elevation Myocardial Infarction | ColchicineChina
-
NYU Langone HealthNational Heart, Lung, and Blood Institute (NHLBI); Population Health Research...Active, not recruitingSTEMI - ST Elevation Myocardial Infarction | Neutrophils.Hypersegmented | Bld-Ser-PlasUnited States
-
Population Health Research InstituteActive, not recruitingIntracranial HemorrhagesCanada
-
Bakulev Scientific Center of Cardiovascular SurgeryCompletedAtrial Fibrillation New Onset | Colchicine Adverse ReactionRussian Federation
-
Population Health Research InstituteCanadian Institutes of Health Research (CIHR)CompletedAtrial Fibrillation | Thoracic SurgeryCanada
-
Population Health Research InstituteRecruitingInflammation | Peripheral Arterial Disease | Atherosclerosis of ExtremitiesCanada
-
Wuhan Union Hospital, ChinaCompletedCoronary Artery Disease | Percutaneous Coronary InterventionChina
-
Eunice Kennedy Shriver National Institute of Child...National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...CompletedObesity | Metabolic DiseaseUnited States
-
Montreal Heart InstituteCompletedMyocardial Infarction | Coronary Artery DiseaseCanada