CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine

NCT06158698 | Recruiting Phase 3 DMC

• 2 other identifiers: CMP-MYTHiCPNRR-MAD-2022-12376225
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 10

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 prospective registry to assess the prognostic value of positive genetic testing in this population.

Conditions

Cardiomyopathies; Myocarditis; Inflammatory Cardiomyopathy; Heart Failure; Ventricular Arrythmia

Keywords

treatment; trial; colchicine; registry; inflammation; outcome; genetic testing

Outcome Measures

Primary Outcomes (2)

• Patients alive and free of any worsening features (clinical, arrhythmic burden and imaging outcome) AND that show at least one of the signs of improvements (IMAGING or ARRHYTMIC improvements).

  Clinical worsening (at least one of the following): 1. cardiac death 2. hospitalization for worsening HF or arrhythmic events, 3. Sustained ventricular tachycardia (SVT). Worsening arrhythmic burden: 1. PVC burden increase of 50% on ECG ambulatory monitoring 2. Increase in NSVT of 30% compared with baseline 3. Any SVT.

  6 months from randomization

• Worsening imaging outcomes

  1. Proportion of patients with LVEF reduction \>10%on echo/CMRI, 2. Proportion of patients with new areas of edema on CMRI or FDG-PET associated with an increase in the edema in the inflammatory lesion identified on baseline CMRI or FDG-PET. Improvement of imaging outcome: 1. Proportion of patients with a reduction in edema on CMRI or FDG without new areas of edema AND normal high sensitivity troponin. 2. Proportion of patients with disappearance of edema on CMRI OR NO FDG uptake on PET Improvement of arrhythmic outcome: 1\. Improvement of ARRHYTHMIC burden. Proportion of patients with a PVC burden reduction of 70% on the ECG ambulatory monitoring and no NSVT/SVT.

  6 months from randomization

Secondary Outcomes (9)

• LVEF change on echocardiogram.

  6 months from randomization

• LVEF change on CMRI

  6 months from randomization

• Evidence of dysfunction and/or dilation on CMRI

  6 months from randomization

• Clinical secondary endpoints

  6 months from randomization

• Mortality

  6 months from randomization

Other Outcomes (2)

• The primary aim of the REGISTRY is the proportion of patients with MCGV(+) Infl-CMP versus MCGV(-) Infl-CMP with more primary endpoints

  Minimum follow up at 6 months

• Differences in the results of in-vitro experiments between MCGV(+) vs. MCGV(-) Infl-CMP patients and between MCGV(+) Infl-CMP patients and family members of the probands with the negative cardiac phenotype (FMPNCP)

  Minimum follow up at 6 months

Study Arms (2)

Colchicine

EXPERIMENTAL

Patients treated with colchicine 0.5-1 mg (1 mg if tolerated) for 6 months.

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

Patients treated with placebo tablets.

Other: Placebo

Interventions

Colchicine DRUG

Colchicine 1 mg daily (or 0.5 mg daily il weight \<70 kg) from randomization for 180 days (6 months)

Also known as: Treatment

Colchicine

Placebo OTHER

Placebo 1 mg daily (or 0.5 mg daily il weight \<70 kg) from randomization for 180 days (6 months)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• European Union: collaborator
• Ministry of Health, Italy: collaborator
• University of Milano Bicocca: collaborator
• Niguarda Hospital: lead
• Mario Negri Institute for Pharmacological Research: collaborator

Study Sites (10)

Università degli studi della Campania L.Vanvitelli e Azienda Ospedaliera Specialistica dei Colli - Ospedale Monaldi

Naples, Campania, 80131, Italy

RECRUITING

Policlinico S.Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

Azienda Sanitaria Universitaria Integrata Giuliano Isontina, Trieste

Trieste, Friuli Venezia Giulia, 34128, Italy

RECRUITING

Presidio Ospedaliero Universitario "Santa Maria della Misericordia"

Udine, Friuli Venezia Giulia, 33100, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 800168, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20169, Italy

RECRUITING

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

RECRUITING

Università Politecnica delle Marche e AOU Ospedali Riuniti Umberto I°-Lancisi-Salesi , Ancona

Ancona, The Marches, 60126, Italy

RECRUITING

ASL8 Arezzo San Donato Hospital

Arezzo, Tuscany, 52100, Italy

RECRUITING

Related Publications (11)

• Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, Friedrich MG, Klingel K, Lehtonen J, Moslehi JJ, Pedrotti P, Rimoldi OE, Schultheiss HP, Tschope C, Cooper LT Jr, Camici PG. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ Heart Fail. 2020 Nov;13(11):e007405. doi: 10.1161/CIRCHEARTFAILURE.120.007405. Epub 2020 Nov 12.

  PMID: 33176455 BACKGROUND

• Ammirati E, Raimondi F, Piriou N, Sardo Infirri L, Mohiddin SA, Mazzanti A, Shenoy C, Cavallari UA, Imazio M, Aquaro GD, Olivotto I, Pedrotti P, Sekhri N, Van de Heyning CM, Broeckx G, Peretto G, Guttmann O, Dellegrottaglie S, Scatteia A, Gentile P, Merlo M, Goldberg RI, Reyentovich A, Sciamanna C, Klaassen S, Poller W, Trankle CR, Abbate A, Keren A, Horowitz-Cederboim S, Cadrin-Tourigny J, Tadros R, Annoni GA, Bonoldi E, Toquet C, Marteau L, Probst V, Trochu JN, Kissopoulou A, Grosu A, Kukavica D, Trancuccio A, Gil C, Tini G, Pedrazzini M, Torchio M, Sinagra G, Gimeno JR, Bernasconi D, Valsecchi MG, Klingel K, Adler ED, Camici PG, Cooper LT Jr. Acute Myocarditis Associated With Desmosomal Gene Variants. JACC Heart Fail. 2022 Oct;10(10):714-727. doi: 10.1016/j.jchf.2022.06.013. Epub 2022 Sep 7.

  PMID: 36175056 BACKGROUND

• Artico J, Merlo M, Delcaro G, Cannata A, Gentile P, De Angelis G, Paldino A, Bussani R, Ferro MD, Sinagra G. Lymphocytic Myocarditis: A Genetically Predisposed Disease? J Am Coll Cardiol. 2020 Jun 23;75(24):3098-3100. doi: 10.1016/j.jacc.2020.04.048. No abstract available.

  PMID: 32553263 BACKGROUND

• Ammirati E, Moslehi JJ. Diagnosis and Treatment of Acute Myocarditis: A Review. JAMA. 2023 Apr 4;329(13):1098-1113. doi: 10.1001/jama.2023.3371.

  PMID: 37014337 BACKGROUND

• Kontorovich AR, Patel N, Moscati A, Richter F, Peter I, Purevjav E, Selejan SR, Kindermann I, Towbin JA, Bohm M, Klingel K, Gelb BD. Myopathic Cardiac Genotypes Increase Risk for Myocarditis. JACC Basic Transl Sci. 2021 Jul 26;6(7):584-592. doi: 10.1016/j.jacbts.2021.06.001. eCollection 2021 Jul.

  PMID: 34368507 BACKGROUND

• Lota AS, Hazebroek MR, Theotokis P, Wassall R, Salmi S, Halliday BP, Tayal U, Verdonschot J, Meena D, Owen R, de Marvao A, Iacob A, Yazdani M, Hammersley DJ, Jones RE, Wage R, Buchan R, Vivian F, Hafouda Y, Noseda M, Gregson J, Mittal T, Wong J, Robertus JL, Baksi AJ, Vassiliou V, Tzoulaki I, Pantazis A, Cleland JGF, Barton PJR, Cook SA, Pennell DJ, Garcia-Pavia P, Cooper LT Jr, Heymans S, Ware JS, Prasad SK. Genetic Architecture of Acute Myocarditis and the Overlap With Inherited Cardiomyopathy. Circulation. 2022 Oct 11;146(15):1123-1134. doi: 10.1161/CIRCULATIONAHA.121.058457. Epub 2022 Sep 26.

  PMID: 36154167 BACKGROUND

• Lakkireddy D, Turagam MK, Yarlagadda B, Dar T, Hamblin M, Krause M, Parikh V, Bommana S, Atkins D, Di Biase L, Mohanty S, Rosamond T, Carroll H, Nydegger C, Wetzel L, Gopinathannair R, Natale A. Myocarditis Causing Premature Ventricular Contractions: Insights From the MAVERIC Registry. Circ Arrhythm Electrophysiol. 2019 Dec;12(12):e007520. doi: 10.1161/CIRCEP.119.007520. Epub 2019 Dec 16.

  PMID: 31838913 BACKGROUND

• Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L'Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16.

  PMID: 31733140 BACKGROUND

• Vandenburgh H, Shansky J, Benesch-Lee F, Barbata V, Reid J, Thorrez L, Valentini R, Crawford G. Drug-screening platform based on the contractility of tissue-engineered muscle. Muscle Nerve. 2008 Apr;37(4):438-47. doi: 10.1002/mus.20931.

  PMID: 18236465 BACKGROUND

• Stoehr A, Neuber C, Baldauf C, Vollert I, Friedrich FW, Flenner F, Carrier L, Eder A, Schaaf S, Hirt MN, Aksehirlioglu B, Tong CW, Moretti A, Eschenhagen T, Hansen A. Automated analysis of contractile force and Ca2+ transients in engineered heart tissue. Am J Physiol Heart Circ Physiol. 2014 May;306(9):H1353-63. doi: 10.1152/ajpheart.00705.2013. Epub 2014 Feb 28.

  PMID: 24585781 BACKGROUND

• Ammirati E, Cartella I, Ciabatti M, Colombo G, Masetti M, Pieroni M, Gallone G, Peretto G, Potena L, Scacciavillani R, Raineri C, Caputo A, Pedrotti P, Sormani P, Conti N, Merlo M, Imazio M, Pani A, Ciliberti ML, Gentile P, Pontone G, Villatore A, Pezzullo E, Palazzini M, Casella M, Valsecchi MG, Burzotta F, Carmina V, Garascia A, Scarale AF, Bernasconi DP, Loffredo FS, Narducci ML. Colchicine in patients with chronic inflammatory cardiomyopathy: rationale and design of the CMP-MYTHiC. ESC Heart Fail. 2026 Mar 3;13(2):xvag058. doi: 10.1093/eschf/xvag058.

  PMID: 41730291 DERIVED

MeSH Terms

Conditions

Cardiomyopathies; Myocarditis; Heart Failure; Inflammation

Interventions

Colchicine; Therapeutics

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Enrico Ammirati, MD, PhD

  ASST Grande Ospedale Metropolitano Niguarda

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Enrico Ammirati, MD, PhD

CONTACT

0264447791; enrico.ammirati@ospedaleniguarda.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-parallel groups randomized, single-blinded, multi-center phase III-controlled trial

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: December 6, 2023
• Study Start: November 14, 2023
• Primary Completion: May 2, 2026
• Study Completion (Estimated): May 2, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (10)