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

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-wor...

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Detalles Bibliográficos
Autores: McLaughlin, Vallerie V., Jansa, Pavel, Nielsen-Kudsk, Jens E., Halank, Michael, Simonneau, Gérald, Grünig, Ekkehard, Ulrich, Silvia, Rosenkranz, Stephan, Gómez Sánchez, Miguel A., Pulido, Tomás, Pepke-Zaba, Joanna, Barberà i Mir, Joan Albert, Hoeper, Marius M, Vachiéry, Jean-Luc, Lang, Irene, Carvalho, Francine, Meier, Christian, Mueller, Katharina, Nikkho, Sylvia, D'Armini, Andrea M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/123223
Acceso en línea:https://hdl.handle.net/2445/123223
Access Level:acceso abierto
Palabra clave:Hipertensió pulmonar
Malalties de l'aparell respiratori
Assaigs clínics
Pulmonary hypertension
Respiratory organs diseases
Clinical trials
Descripción
Sumario: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.