Status:
RECRUITING
CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
Lead Sponsor:
Niguarda Hospital
Collaborating Sponsors:
European Union
Ministry of Health, Italy
Conditions:
Cardiomyopathies
Myocarditis
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
Two-parallel groups randomized, single-blinded, multi-center phase III controlled trial in patients with chronic inflammatory cardiomyopathy to assess the efficacy of colchicine and associated prospec...
Detailed Description
In a proportion of patients, myocarditis, an inflammatory injury of cardiomyocytes (CMs), can lead to chronic inflammatory cardiomyopathy (Infl-CMP) characterized by an increased risk of life-threaten...
Eligibility Criteria
Inclusion
- Inclusion Criteria Trial and Registry:
- Males and females with Infl-CMP associated with VA (including high PVC burden), reduced LVEF, or significantly increased levels of natriuretic peptides.
- Patients of 18 years or older
- Evidence of myocardial inflammation on CMRI (using 2018 Lake Louis criteria) or FDG-PET performed in the 3 months before randomization to be included in the trial OR in the last 12 months before for the registry.
- Presence of any of the following characteristics and if symptoms have been present for more than 1 month:
- Mono-morphic or polymorphic PVC burden of ≥3000 in 24 hours, or NSVTs (defined as \>3 more consecutive beat lasting \<30 seconds) or evidence of sustained ventricular tachycardias (SVT).
- Reduced LVEF on echocardiogram (\<50%) or on CMRI (\<60%)-. Increased N-terminal pro-B-type natriuretic peptide (NT- proBNP) concentration of 1000 pg/mL or more, or a B-type natriuretic peptide (BNP) concentration of 200 pg/mL or more
- Persistence of increased high-sensitivity troponin levels above the upper reference limit (URL) after at least 2 months from the first assessment and at least a mono-morphic or polymorphic PVC burden of ≥1000 in 24 hours.
- Exclusion Criteria Registry:
- Proven history of myocardial infarction with evidence of ischemic scar on echocardiogram or CMRI,
- Significant flow-limiting coronary artery disease (stenosis above 50%) on invasive coronary angiography or computed tomography (CT) coronary angiography,
- Cardiomyopathy attributed to toxins such as alcohol and illicit drugs, or to specific causes (i.e. amyloidosis or hypertrophic cardiomyopathy)
- Known systemic autoimmune disorder (the exception will be for patients with systemic autoimmune disease or isolated cardiac sarcoidosis with a family history of cardiomyopathy, myocarditis, or arrhythmias, where overlap between an autoimmune event and a genetic background can occur). These patients will undergo genetic tests. Patients with autoimmune systemic disorders and isolated cardiac sarcoidosis with positive genetic tests for MCVG will be included in the registry.
- Previous history of cardiac surgery for instance correction of congenital heart disease or a valve repair/replacement
- Known chronic infective disease, such as HIV infection or tuberculosis
- Participants involved in another clinical trial, defined by the participation in a clinical trial in which an investigational drug was administered in the 30 days prior to screening, or 5 half-lives of the study drug, whichever is longer;
- Any other significant disease or disorder which (expected life expectancy \<12 months), in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial or the participant's ability to participate in the trial.
- Exclusion Criteria Trial :
- Proven history of myocardial infarction with evidence of ischemic scar on echocardiogram or CMRI,
- Significant flow-limiting coronary artery disease (stenosis above 50%) on invasive coronary angiography or computed tomography (CT) coronary angiography,
- Cardiomyopathy attributed to toxins such as alcohol and illicit drugs, or to specific causes (i.e. amyloidosis or hypertrophic cardiomyopathy)
- Known systemic autoimmune disorder (the exception will be for patients with systemic autoimmune disease or isolated cardiac sarcoidosis with a family history of cardiomyopathy, myocarditis, or arrhythmias, where overlap between an autoimmune event and a genetic background can occur). These patients will undergo genetic tests. Patients with autoimmune systemic disorders and isolated cardiac sarcoidosis with positive genetic tests for MCVG will be included in the registry.
- Previous history of cardiac surgery for instance correction of congenital heart disease or a valve repair/replacement
- Known chronic infective disease, such as HIV infection or tuberculosis
- Participants involved in another clinical trial, defined by the participation in a clinical trial in which an investigational drug was administered in the 30 days prior to screening, or 5 half-lives of the study drug, whichever is longer;
- Any other significant disease or disorder which (expected life expectancy \<12 months), in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial or the participant's ability to participate in the trial.
- Women with childbearing potential (this exclusion criterion is due to insufficient human information regarding the embryofoetal risk with colchicine)
- Current symptomatic atrial arrhythmias (including persistent atrial fibrillation) associated with LV dysfunction,
- Advance heart failure (NYHA III or need for inotropes including levosimendan), or recurrent VA despite previous catheter ablation,
- Known systemic autoimmune disorder or other conditions at the time of randomization where immunosuppression is assumed useful (i.e. cardiac sarcoidosis),
- Patients already on chronic immunosuppressive therapies (including colchicine) or in whom immunosuppressive therapy is deemed necessary
- Contraindication to colchicine, including allergies to this medication and its excipients (i.e., lactose and sucrose),
- Impaired renal function (eGFR\<30 ml/min/1.73m2),
- Known history of hepatic cirrhosis or transaminase levels at baseline \> x3-fold the URL
- Patients with peripheral eosinophilia (eosinophil count \>10% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization.
- Severe gastrointestinal insufficiency (for instance, malabsorption syndrome, severe chronic diarrhea)
- Women during breastfeeding
Exclusion
Key Trial Info
Start Date :
November 14 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
May 2 2028
Estimated Enrollment :
80 Patients enrolled
Trial Details
Trial ID
NCT06158698
Start Date
November 14 2023
End Date
May 2 2028
Last Update
December 13 2024
Active Locations (10)
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1
Università degli studi della Campania L.Vanvitelli e Azienda Ospedaliera Specialistica dei Colli - Ospedale Monaldi
Napoli, Campania, Italy, 80131
2
Policlinico S.Orsola-Malpighi
Bologna, Emilia-Romagna, Italy, 40138
3
Azienda Sanitaria Universitaria Integrata Giuliano Isontina, Trieste
Trieste, Friuli Venezia Giulia, Italy, 34128
4
Presidio Ospedaliero Universitario "Santa Maria della Misericordia"
Udine, Friuli Venezia Giulia, Italy, 33100