Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study

BMC Pulmonary Medicine

Research Article

Irene Lang¹  Katharina Mueller²  Pavel Jansa³  Marius M. Hoeper⁴  Silvia Ulrich⁵  Stephan Rosenkranz⁶  Jens E. Nielsen-Kudsk⁷  Joan Albert Barberá⁸  Andrea M. D’Armini⁹  Jean-Luc Vachiéry^1,10  Sylvia Nikkho^1,11  Francine Carvalho^1,12  Christian Meier^1,13  Gérald Simonneau^1,14  Tomás Pulido^1,15  Joanna Pepke-Zaba^1,16  Ekkehard Grünig^1,17  Miguel A. Gómez Sánchez^1,18  Michael Halank^1,19  Vallerie V. McLaughlin^2,20 

[1] Allgemeines Krankenhaus der Stadt Wien, Medizinische Universität Wien, Wien, Austria;Bayer AG, Wuppertal, Germany;Cardiology and Angiology Department, General University Hospital, Prague, Czech Republic;Clinic for Respiratory Medicine, Hannover Medical School, Hannover, Germany;Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland;Department III of Internal Medicine, Cologne University Heart Center, Cologne, Germany;Department of Cardiological Medicine, Aarhus University, Aarhus, Denmark;Department of Pulmonary Medicine, Hospital Clínic-IDIBAPS, University of Barcelona, and Biomedical Research Networking Center on Respiratory Diseases, Madrid, Spain;Division of Cardiothoracic Surgery, Foundation “IRCCS Policlinico San Matteo”, University of Pavia School of Medicine, Pavia, Italy;Département de Cardiologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium;Global Clinical Development, Bayer AG, Berlin, Germany;Global Development, Bayer SA, São Paulo, Brazil;Global Medical Affairs, Bayer AG, Berlin, Germany;Hôpital Bicêtre, Université Paris-Sud, Laboratoire d’Excellence en Recherche sur le Médicament et Innovation Thérapeutique, and INSERM Unité 999, Paris, France;Instituto Nacional de Cardiología, Mexico City, Mexico;National Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridge, UK;Thoraxclinic, University Hospital Heidelberg, Heidelberg, Germany;Unidad de I. Cardiaca e Hipertensión Pulmonar, Hospital Universitario 12 de Octubre, Madrid, Spain;University Hospital Dresden, Dresden, Germany;University of Michigan Health System, 1011 Cornwell Pl, 48104, Ann Arbor, USA;

关键词: Riociguat;    Chronic thromboembolic pulmonary hypertension;    Early access study;   

DOI  :  10.1186/s12890-017-0563-7

 received in 2017-07-04, accepted in 2017-12-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundFollowing positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH.MethodsWe performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints.ResultsIn total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups.ConclusionsRiociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed.Trial registrationClinicalTrials.org NCT01784562. Registered February 4, 2013.

【 授权许可】

CC BY   
© The Author(s). 2017