title: New trial designs and potential therapies for pulmonary artery hypertension.
abstract: A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH.
authors.affiliation: Section of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois. Electronic address: mgomberg@bsd.uchicago.edu.
authors.forename: Mardi
authors.initials: M
authors.lastname: Gomberg-Maitland
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Bull
authors.affiliation: Heart and Lung Institute, Phoenix, Arizona.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Saggar
authors.affiliation: Columbia University, New York, New York.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.affiliation: European Medicine Agency, London, England.
authors.forename: Amany
authors.initials: A
authors.lastname: Elgazayerly
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.affiliation: Section of Pulmonary, Department of Medicine, Department of Medical Oncology, University Hospital Giessen, Giessen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: AbaNovus, San Remo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rainisio
authors.affiliation: Section of Cardiology, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.affiliation: Food and Drug Administration, White Oak, Maryland.
authors.forename: Norman
authors.initials: N
authors.lastname: Stockbridge
authors.affiliation: Section of Cardiology, Department of Medicine, University of Bologna, Bologna, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ventura
authors.affiliation: Section of Pulmonary, Department of Medicine, Department of Medical Oncology, University Hospital Giessen, Giessen, Germany.
authors.forename: Ardeschir H
authors.initials: AH
authors.lastname: Ghofrani
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of California San Diego, San Diego, California.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends*; D055808:Drug Discovery / Q000639:trends*; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000628:therapy*; D012107:Research Design / Q000639:trends*
keywords: 6-min walk distance; 6MWD; ECMO; EPC; FAO; LV; MSC; NO; PAH; PDGF; PH; PRO; PVR; RAAS; RV; TTCW; VEGF; eNOS; endothelial nitric oxide synthase; endothelial progenitor cell; ethics; extracorporeal membrane oxygenation; fatty acid oxygenation; left ventricle/ventricular; mesenchymal stem cell; nitric oxide; patient-reported outcome; platelet-derived growth factor; pulmonary arterial hypertension; pulmonary hypertension; pulmonary vascular resistance; renin-angiotensin-aldosterone system; right ventricle/ventricular; therapeutics; time to clinical worsening; trial designs; vascular endothelial growth factor