RT Journal Article
SR Electronic
T1 Effect of macitentan on morbidity and mortality in pulmonary arterial hypertension: A randomised controlled trial (SERAPHIN)
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1786
VO 42
IS Suppl 57
A1 Hossein-Ardeschir Ghofrani
A1 Richard Channick
A1 Marion Delcroix
A1 Nazzareno Galiè
A1 Pavel Jansa
A1 Franck-Olivier Le Brun
A1 Sanjay Mehta
A1 Camilla Mittelholzer
A1 Tomás Pulido
A1 B.K.S. Sastry
A1 Olivier Sitbon
A1 Rogério Souza
A1 Adam Torbicki
A1 Lewis Rubin
A1 Gérald Simonneau
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/1786.abstract
AB The effect of macitentan, a novel dual endothelin receptor antagonist, on morbidity and mortality was assessed in patients with pulmonary arterial hypertension (PAH). In this double-blind, placebo-controlled, Phase III, event-driven study (SERAPHIN; NCT00660179), 742 PAH patients (≥12 years) were randomised to placebo (n=250), macitentan 3mg (n=250) or 10mg (n=242) once daily. 64% received PAH-specific drugs at baseline. Mean treatment duration was 85.3, 99.5 and 103.9 weeks, respectively. The primary endpoint was time from treatment initiation to first morbidity or mortality event (death, atrial septostomy, lung transplantation, initiation of i.v./s.c. prostanoids or PAH worsening – blindly and independently adjudicated). Macitentan reduced the risk of such an event vs placebo by 30% (97.5%CI: 4–48%; P=0.0108) in the 3mg group and 45% (97.5%CI: 24–61%; P<0.0001) in the 10mg group. This effect was established early, sustained over the entire study duration and, for the 10mg dose, was preserved across WHO functional class (FC), as well as in combination with other PAH-specific drugs. Macitentan 3mg and 10mg reduced the risk of PAH-related death or hospitalisation (a composite secondary endpoint) by 33% (97.5%CI: 3–54%; P=0.0146) and 50% (97.5%CI: 25–67%; P<0.0001). Macitentan was well tolerated; incidences of elevated liver aminotransferases and peripheral oedema were similar across groups. Headache, nasopharyngitis and anaemia occurred more frequently with macitentan than placebo. In conclusion, macitentan significantly reduced morbidity and mortality in patients with PAH, with a favourable safety profile.