BACKGROUND: Following 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Riociguat 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 REGISTRATION: ClinicalTrials.org NCT01784562 . Registered February 4, 2013.

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

Département de Cardiologie Hôpital Erasme Université Libre de Bruxelles Brussels Belgium

Department 3 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

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 1 Cardiaca e Hipertensión Pulmonar Hospital Universitario 12 de Octubre Madrid Spain

University Hospital Dresden Dresden Germany

University of Michigan Health System 1011 Cornwell Pl Ann Arbor 48104 USA

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NCT01784562