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

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.

Timeline

Start

2023-11-14

Primary completion

2026-05-02

Completion

2028-05-02

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications