{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:21:31Z","timestamp":1771467691925,"version":"3.50.1"},"reference-count":12,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bayer Yakuhin Ltd, Bayer AG","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp & Dohme Corp.","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Merck & Co., Inc","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,6,21]]},"published-print":{"date-parts":[[2023,7]]},"abstract":"\n Objectives<\/jats:title>\n Balloon pulmonary angioplasty (BPA) and medical therapy, such as soluble guanylate cyclase stimulators, are recommended treatments for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA). However, monotherapy with BPA or medical therapy cannot always eliminate symptoms such as exertional dyspnoea. Thus, this study aims to clarify the efficacy of continuous treatment with riociguat in inoperable CTEPH patients with normalised haemodynamics after BPA.<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n This is a double-blind, multicentre, randomised, placebo-controlled trial. Participants with CTEPH who are ineligible for PEA will receive riociguat followed by BPA. Subsequently, participants will be randomised (1:1) into either riociguat continuing or discontinuing groups and will be observed for 16\u2009weeks after randomisation. The primary endpoint will be the change in peak cardiac index (CI) during the cardiopulmonary exercise test. In the primary analysis, the least square mean differences and 95% CIs for the change in peak CI at 16\u2009weeks between the groups will be estimated by a linear mixed-effects model with baseline value as a covariate, treatment group as a fixed effect and study institution as a random effect.<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n National Hospital Organisation Review Board for Clinical Trials (Nagoya) and each participating institution approved this study and its protocols. Written informed consent will be obtained from all participants. The results will be disseminated at medical conferences and in journal publications.<\/jats:p>\n <\/jats:sec>\n \n Registration details<\/jats:title>\n \n Japan Registry of Clinical Trials: jRCT no. 041200052. ClinicalTrials.gov by National Library of Medicine Registry ID:\n NCT04600492<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n NCT04600492<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-072241","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T16:43:42Z","timestamp":1688575422000},"page":"e072241","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Protocol for a multicentre, double-blind, randomised, placebo-controlled trial of riociguat on peak cardiac index during exercise in patients with chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty (THERAPY-HYBRID-BPA trial)"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04600492","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04600492","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04600492","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-9532","authenticated-orcid":false,"given":"Hiroto","family":"Shimokawahara","sequence":"first","affiliation":[{"name":"Department of Cardiology, NHO Okayama Medical Center, Okayama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Inami","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyorin University Hospital, Mitaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayoko","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate school of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroya","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Core Laboratory, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko M","family":"Saito","sequence":"additional","affiliation":[{"name":"Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Sekimizu","sequence":"additional","affiliation":[{"name":"Clinical Research Center, NHO Nagoya Medical Center, Nagoya, 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