• Vallerie V McLaughlin, Pavel Jansa, Jens E Nielsen-Kudsk, Michael Halank, Gérald Simonneau, Ekkehard Grünig, Silvia Ulrich, Stephan Rosenkranz, Miguel A Gómez Sánchez, Tomás Pulido, Joanna Pepke-Zaba, Joan Albert Barberá, Marius M Hoeper, Jean-Luc Vachiéry, Irene Lang, Francine Carvalho, Christian Meier, Katharina Mueller, Sylvia Nikkho, and Andrea M D'Armini.
• University of Michigan Health System, 1011 Cornwell Pl, Ann Arbor, 48104, USA. vmclaugh@med.umich.edu.
• BMC Pulm Med. 2017 Dec 28; 17 (1): 216.

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.

30 keywords...

hide…