Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial
| Autor: | Katerina M. Antoniou, Julien Guiot, Mordechai R. Kramer, Athol U. Wells, Jürgen Behr, Klaus Uwe Kirchgaessler, Steven D. Nathan, Monica Bengus, Andras Perjesi, Sergio Harari, Demosthenes Bouros, Nesrin Mogulkoc Bishop, Wim A. Wuyts, Frank Gilberg |
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| Přispěvatelé: | Ege Üniversitesi |
| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male medicine.medical_specialty Sildenafil Pyridones Nintedanib Hypertension Pulmonary Population Placebo Sildenafil Citrate 03 medical and health sciences chemistry.chemical_compound Idiopathic pulmonary fibrosis 0302 clinical medicine Double-Blind Method Internal medicine medicine Humans 030212 general & internal medicine education Pulmonary wedge pressure Adverse effect Aged education.field_of_study Capacity business.industry Bosentan Pirfenidone medicine.disease Pulmonary hypertension Idiopathic Pulmonary Fibrosis respiratory tract diseases 030228 respiratory system chemistry Drug Therapy Combination Female Therapy business medicine.drug |
| Zdroj: | Lancet Resp. Med. 9, 85-95 (2021) |
| ISSN: | 2213-2619 |
| Popis: | Background: The benefit of sildenafil in patients with advanced idiopathic pulmonary fibrosis (IPF) at risk of poor outcomes from pulmonary hypertension, whether already present or likely to develop, is uncertain. We aimed to assess the efficacy and safety of sildenafil added to pirfenidone versus placebo added to pirfenidone for 52 weeks in patients with advanced IPF and at risk of group 3 pulmonary hypertension. Methods: We did a multicentre, international, double-blind, randomised, placebo-controlled, phase 2b study at 56 university clinics, research hospitals, and tertiary sites in Canada, Europe (Belgium, Czech Republic, Germany, Greece, Hungary, Italy, the Netherlands, Spain, and Turkey), Israel, and Africa (Egypt and South Africa). Eligible patients (aged 40–80 years) had advanced IPF (carbon monoxide diffusing capacity ?40% predicted at screening), and were at risk of group 3 pulmonary hypertension (mean pulmonary artery pressure of ?20 mm Hg with pulmonary artery wedge pressure of ?15 mm Hg on previous right-heart catheterisation, or intermediate or high probability of group 3 pulmonary hypertension on echocardiography as defined by the 2015 European Society of Cardiology and European Respiratory Society guidelines). Patients were randomly assigned 1:1 to oral sildenafil tablets (20 mg three times daily) or placebo, both in addition to oral pirfenidone capsules (801 mg three times daily), using a validated interactive voice-based or web-based response system with permuted block randomisation, stratified by previous right-heart catheterisation (yes or no) and forced expiratory volume in 1 s to forced vital capacity ratio ( Actelion Pharmaceuticals Boehringer Ingelheim GlaxoSmithKline, GSK Fondazione Internazionale Menarini F. Hoffmann-La Roche CMC Microsystems, CMC F. Hoffmann-La Roche JB has received personal fees for lectures and consulting services from Actelion, Boehringer Ingelheim, F Hoffmann-La Roche, Pliant, Promedior (acquired by F Hoffmann-La Roche in February 2020), MSD, Bristol-Myers Squibb, Novartis, AstraZeneca, and Galapagos, outside of the submitted work; and is a member of national and international guideline committees for idiopathic pulmonary fibrosis (IPF). SDN is a consultant and is on the speakers' bureau for Boehringer Ingelheim and F Hoffmann-La Roche; is also a consultant for Bellerophon, and United Therapeutics; and his institution has received research funding from Boehringer Ingelheim and F Hoffmann-La Roche, all outside of the submitted work. WAW has received consulting fees and lecture fees from Boehringer Ingelheim and F Hoffmann-La Roche, paid to his institution, outside of the submitted work. NMB has received lecture fees from Actelion, Boehringer Ingelheim, and F Hoffmann-La Roche, outside of the submitted work. DEB has received personal fees for lectures and consulting services from Boehringer Ingelheim and F Hoffmann-La Roche; his institution has received research funding from Boehringer Ingelheim and F Hoffmann-La Roche, all outside of the submitted work; and he is a member of international guideline committees for IPF. KA has received consulting and lecture fees from Boehringer Ingelheim, F Hoffmann-La Roche, GlaxoSmithKline, and Menarini; her institution has received sponsorship and research funding from Boehringer Ingelheim and F Hoffmann-La Roche, all outside of the submitted work. JG has received consulting and lecture fees from Actelion, Boehringer Ingelheim, F Hoffmann-La Roche, and GlaxoSmithKline; his institution has received research fees from Actelion, Boehringer Ingelheim, and F Hoffmann-La Roche, all outside of the submitted work. K-UK and MB are employees and shareholders of F Hoffmann-La Roche. FG and AP are employees of F Hoffmann-La Roche. SH has served as a consultant for, received speakers' bureau fees from, and received research funding from Actelion, Boehringer Ingelheim, and F Hoffmann-La Roche, outside of the submitted work. AUW has received consulting and lecture fees from Boehringer Ingelheim, F Hoffmann-La Roche, and Blade Therapeutics, outside of the submitted work. MRK declares no competing interests. We thank Jean-Marc Haeusler of F Hoffmann-La Roche for his support, feedback, and insights during the study, and Anna Wollenberg of F Hoffmann-La Roche for her ongoing support with this study. We also thank the independent data monitoring committee members: Marc Humbert (Chair), Carlo Albera, and Diethelm Messinger. We thank the patients, their family members, and participating staff at all of the study centres. Medical writing support was provided by Ceilidh McConnachie and Catherine Stanton of CMC AFFINITY, McCann Health Medical Communications, funded by F Hoffmann-La Roche. |
| Databáze: | OpenAIRE |
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