The efficacy and safety of macitentan in Fontan-palliated patients: results of the 52-week randomised, placebo-controlled RUBATO trial

Abstract Background The clinical utility and long-term effects of endothelin receptor antagonists (ERAs) in Fontan-palliated patients remain unclear there are currently no approved therapies. A decline peak VO2 between consecutive cardiopulmonary exercise tests (CPETs) is highly prognostic for death or transplant adult Fontan patients, hence its use as a primary endpoint trials ERAs with circulation. Purpose RUBATO trial aimed to assess the efficacy safety macitentan, an antagonist, over 52 weeks. Methods In multicentre, double-blind, randomised, placebo-controlled, phase 3 trial, were randomised 1:1 macitentan 10 mg once-daily placebo Eligible aged ≥12 years, New York Heart Association functional class II III, had limitations CPET (including pacemakers), undergone lateral tunnel extracardiac conduit (total cavopulmonary connection) >1 year before screening showed signs failure deterioration within months screening. Primary was change from baseline week 16. Secondary endpoints weeks mean count per minute daily physical activity 16 measured by accelerometer. Adverse events also assessed. Results 137 (n=68) (n=69). 92.7% completed double-blind treatment: 7 prematurely discontinued study treatment arms, respectively. Patient characteristics shown Table 1. At 16, (SD) –0.16 (2.86) vs –0.67 (2.66) mL/kg/min (median unbiased estimate difference placebo: 0.62 [99% repeated confidence interval –0.62; 1.85], p=0.1930). No effect observed two secondary (Table 2): decreased 3.02 (92.44) 14.34 (117.56) (p=0.4512). most common AEs headache (10.3% 8.7% on placebo), nasopharyngitis (5.9% 4.3%), pyrexia 4.3%). leading discontinuation reported (4.4%) 1 (1.4%) patients. Conclusion 52-week provides important addition data not met endpoints. Macitentan well tolerated; findings consistent known profile mg. Funding Acknowledgement Type funding sources: Private company. Main source(s): Actelion Pharmaceuticals Ltd., Janssen pharmaceutical company Johnson & Johnson.