Contributors: Pablo, Garcia-Pavia; Jose Fernando Rodriguez, Palomare; Gianfranco, Sinagra; Roberto, Barriales-Villa; Neal K, Lakdawala; Robert L, Gottlieb; Randal I, Goldberg; Perry, Elliott; Patrice, Lee; Huihua, Li; Franca S, Angeli; Daniel P, Judge; Calum A, Macrae; Ripoll Vera, REALM-DCM Investigators REALM-DCM Investigators Tomas V.; Universitario Son Llatzer, Hospital; de Mallorca, Palma; Spain; Mcdonald, Thomas V.; of South Florida, University; Fl, Tampa; Carlos Castillo Dominguez, Juan; Regional Reina Sofia, C. H.; Spain, Córdoba; Katz and Ste phen Pan, Stuart D.; Langone Health, Nyu; York, New; Ny; Gimeno Blanes, Juan R.; Universitario Virgen de la Arrixaca, Hospital; Spain, Murcia; Gupta, Dinesh K.; Center for Clinical Trials, Tennessee; Tn, Tullahoma; Taylor, Matthew R. G.; of Colo rado, University; Co, Aurora; Forleo, Cinzia; Ospedaliero Universitaria Consorziale Policlinico di Bari, Azienda; Italy, Bari; Afshar, Kia; Medical Center, Intermountain; Ut, Murray; Wheeler, Matthew T.; University School of Medicine, Stanford; Ca, Stanford; Priori, Silvia G.; Istituti Clinici Scientifici Maugeri Spa Società Benefit, Ircc; Via, Pa; Italy; Vanderheyden, Marc; Aalst, Onze-Lieve-Vrouwziekenhui; Belgium; copo Olivotto, Ia; Ospedaliera Universitaria Careggi, Azienda; Italy, Florence; Tallaj, Jose A.; Kirklin Clinic of University of Alabama at Birmingham, The; Al, Birmingham; Van Cleemput, Johan; Leuven, Uz; Belgium, Leuven; Garcia Alvarez, Ana; pital Clinic de Barcelona, Ho; Spain, Barcelona; Stempien-Otero, April C.; of Washington Medical Center, University; Wa, Seattle; Alfonso Jimenez Diaz, Victor; Alvaro Cunqueiro, Com plejo Hospitalario Universitario de Vigo - H.; Spain, Vigo; Beatrice Musumeci, Maria; Ospedaliera Sant’Andrea, Azienda; Italy, Rome; Ware, Jame; Brompton Hospital, Royal; London; Kingdom, United; Owens, Anjali T.; of Pennsylvania Heart and Vascular Center, University; Pa, Philadelphia; Cadrin-Tourigny, Julia; Laboratories of Montreal Heart Institute, Clinical; Canada, Montreal; Wilson Tang, W. H.; Cleveland Clinic Foundation, The; Oh, Cleveland; Ewald, Gregory A.; ington University Center for Advanced Medicine, Wash; Louis, Saint; Mo; Maurizio Parato, Vito; Ospedaliero Madonna del Soccorso, Presidio; Benedetto del Tronto, San; Jones, Alonzo E.; Regional Research Institute, Columbu; Ga, Columbu; Ambrosio, Giuseppe; Santa Maria Della Misericordia, Ospedale; Italy, Perugia
نبذة مختصرة : BACKGROUND LMNA (lamin A/C)-related dilated cardiomyopathy is a rare genetic cause of heart failure. In a phase 2 trial and long-term extension, the selective p38 alpha MAPK (mitogen-activated protein kinase) inhibitor, ARRY-371797 (PF-07265803), was associated with an improved 6-minute walk test at 12 weeks, which was preserved over 144 weeks. METHODS REALM-DCM (NCT03439514) was a phase 3, randomized, double-blind, placebo-controlled trial in patients with symptomatic LMNA-related dilated cardiomyopathy. Patients with confirmed LMNA variants, New York Heart Association class II/III symptoms, left ventricular ejection fraction <= 50%, implanted cardioverter-defibrillator, and reduced 6-minute walk test distance were randomized to ARRY-371797 400 mg twice daily or placebo. The primary outcome was a change from baseline at week 24 in the 6-minute walk test distance using stratified Hodges-Lehmann estimation and the van Elteren test. Secondary outcomes using similar methodology included change from baseline at week 24 in the Kansas City Cardiomyopathy Questionnaire-physical limitation and total symptom scores, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration. Time to a composite outcome of worsening heart failure or all-cause mortality and overall survival were evaluated using Kaplan-Meier and Cox proportional hazards analyses. RESULTS REALM-DCM was terminated after a planned interim analysis suggested futility. Between April 2018 and October 2022, 77 patients (aged 23-72 years) received ARRY-371797 (n=40) or placebo (n=37). No significant differences (P>0.05) between groups were observed in the change from baseline at week 24 for all outcomes: 6-minute walk test distance (median difference, 4.9 m [95% CI, -24.2 to 34.1]; P=0.82); Kansas City Cardiomyopathy Questionnaire-physical limitation score (2.4 [95% CI, -6.4 to 11.2]; P=0.54); Kansas City Cardiomyopathy Questionnaire-total symptom score (5.3 [95% CI, -4.3 to 14.9]; P=0.48); and NT-proBNP concentration (-339.4 pg/mL [95% CI, ...
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