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 naive. 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-naive subgroups. CONCLUSIONS: Riociguat was well tolerated in patients with CTEPH who were treatment naive, 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.
- McLaughlin, V. V.
- Jansa, P.
- Nielsen-Kudsk, J. E.
- Halank, M.
- Simonneau, G.
- Grunig, E.
- Ulrich, S.
- Rosenkranz, S.
- Gomez Sanchez, M. A.
- Pulido, T.
- Pepke-Zaba, J.
- Barbera, J. A.
- Hoeper, M. M.
- Vachiery, J. L.
- Lang, I.
- Carvalho, F.
- Meier, C.
- Mueller, K.
- Nikkho, S.
- D'Armini, A. M.
Keywords
- Chronic thromboembolic pulmonary hypertension
- Early access study
- Riociguat
