Clinical trial design and new therapies for pulmonary arterial hypertension
Open Access
- 10 January 2019
- journal article
- research article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 53 (1), 1801908
- https://doi.org/10.1183/13993003.01908-2018
Abstract
Until 20 years ago the treatment of pulmonary arterial hypertension (PAH) was based on case reports and small series, and was largely ineffectual. As a deeper understanding of the pathogenesis and pathophysiology of PAH evolved over the subsequent two decades, coupled with epidemiological studies defining the clinical and demographic characteristics of the condition, a renewed interest in treatment development emerged through collaborations between international experts, industry and regulatory agencies. These efforts led to the performance of robust, high-quality clinical trials of novel therapies that targeted putative pathogenic pathways, leading to the approval of more than 10 novel therapies that have beneficially impacted both the quality and duration of life. However, our understanding of PAH remains incomplete and there is no cure. Accordingly, efforts are now focused on identifying novel pathogenic pathways that may be targeted, and applying more rigorous clinical trial designs to better define the efficacy of these new potential treatments and their role in the management scheme. This article, prepared by a Task Force comprised of expert clinicians, trialists and regulators, summarises the current state of the art, and provides insight into the opportunities and challenges for identifying and assessing the efficacy and safety of new treatments for this challenging condition.Keywords
This publication has 104 references indexed in Scilit:
- Design Issues in Randomized Phase II/III TrialsJournal of Clinical Oncology, 2012
- Neutrophil Elastase Is Produced by Pulmonary Artery Smooth Muscle Cells and Is Linked to Neointimal LesionsThe American Journal of Pathology, 2011
- Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle’s cycleJournal of Molecular Medicine, 2011
- Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial HypertensionCirculation, 2011
- The von Hippel–Lindau Chuvash mutation promotes pulmonary hypertension and fibrosis in miceJCI Insight, 2010
- A Dosing/Cross-Development Study of the Multikinase Inhibitor Sorafenib in Patients With Pulmonary Arterial HypertensionClinical Pharmacology & Therapeutics, 2009
- Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertensionBritish Journal of Pharmacology, 2009
- A meta-analysis of randomized controlled trials in pulmonary arterial hypertensionEuropean Heart Journal, 2008
- Insulin resistance in pulmonary arterial hypertensionEuropean Respiratory Journal, 2008
- An antiproliferative BMP-2/PPARγ/apoE axis in human and murine SMCs and its role in pulmonary hypertensionJCI Insight, 2008