title: Effect of macitentan on hospitalizations: results from the SERAPHIN trial.
abstract: OBJECTIVE
  This study sought to evaluate the effect of macitentan on hospitalization of patients with symptomatic pulmonary arterial hypertension (PAH).
  
  
  BACKGROUND
  PAH is a progressive, life-threatening disease often requiring hospitalization.
  
  
  METHODS
  In the multicenter, double-blind, randomized, event-driven, phase III SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial, patients with symptomatic PAH were randomized (1:1:1) to receive placebo or 3 mg or 10 mg of macitentan. Effects of macitentan on the risk, rate, and number of hospital days for all-cause and PAH-related hospitalizations were compared with those for placebo. Risk and causes of hospitalizations unrelated to PAH were investigated.
  
  
  RESULTS
  Of 742 randomized patients, 250 received placebo, 250 received 3 mg of macitentan, and 242 received 10 mg of macitentan; the overall median duration of treatment was 115 weeks. Risk of all-cause hospitalization was reduced by 18.9% (p = 0.1208) and 32.3% (p = 0.0051) in the macitentan 3-mg and 10-mg arm, respectively. Rates of all-cause hospitalizations and numbers of hospital days were reduced by 20.5% (p = 0.0378) and 30.6% (p = 0.0278), respectively, with 3 mg of macitentan and by 33.1% (p = 0.0005) and 31.0% (p = 0.0336), respectively, with 10 mg of macitentan. Risk of PAH-related hospitalizations were reduced by 42.7% (p = 0.0015) and 51.6% (p < 0.0001) in the macitentan 3-mg and 10-mg arms, respectively. Rate of PAH-related hospitalizations and numbers of hospital days were reduced by 44.5% (p = 0.0004) and 53.3% (p = 0.0001), respectively, with 3 mg of macitentan, and reduced by 49.8% (p < 0.0001) and 52.3% (p = 0.0003), respectively, with 10 mg of macitentan. Risk of non-PAH-related hospitalization was similar between treatment arms.
  
  
  CONCLUSIONS
  Macitentan 10 mg significantly reduced the risk and rate of all-cause hospitalization, which was driven by reductions in the risk and rate of PAH-related hospitalization. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension; NCT00660179).
authors.affiliation: Pulmonary and Critical Care, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: rchannick@mgh.harvard.edu.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Channick
authors.affiliation: Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium.
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Elke
authors.initials: E
authors.lastname: Hunsche
authors.affiliation: Clinical Department of Cardiology and Angiology, 1st Faculty of Medicine, 2nd Medical Department, Charles University, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Jansa
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Franck-Olivier
authors.initials: FO
authors.lastname: Le Brun
authors.affiliation: Division of Respirology, Department of Medicine, London Health Sciences Centre-Victoria Hospital, Western University, London, Ontario, Canada.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Cardiopulmonary Department, Ignacio Chávez National Heart Institute, Mexico City, Mexico.
authors.forename: Tomás
authors.initials: T
authors.lastname: Pulido
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California, San Diego Medical School, San Diego, California.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.affiliation: Department of Cardiology, CARE Hospitals, Hyderabad, India.
authors.forename: B K S
authors.initials: BKS
authors.lastname: Sastry
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Pulmonary Department, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: Souza
authors.affiliation: Department of Pulmonary Circulation and Thromboembolic Diseases, Medical Center of Postgraduate Education, ECZ-Otwock, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Torbicki
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists / Q000008:administration & dosage; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006760:Hospitalization / Q000639:trends*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D065130:Endothelin A Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan
keywords: hospitalization; macitentan; pulmonary arterial hypertension