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)

• Published in: BMJ open 2023-07, Vol.13 (7), p.e072241-e072241
• Main Authors: Shimokawahara, Hiroto, Inami, Takumi, Kubota, Kayoko, Taniguchi, Yu, Hashimoto, Hiroya, Saito, Akiko M, Sekimizu, Masahiro, Matsubara, Hiromi
• Format: Article
• Language: English
• Subjects: Adult cardiology; Angioplasty; Angioplasty, Balloon; Blood pressure; Cardiac catheterization; Cardiac stress tests; Cardiovascular Medicine; Chronic Disease; Clinical trials; Double-blind studies; Dyspnea; Exercise; Heart; Hemodynamics; Humans; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Informed consent; Multicenter Studies as Topic; Nitric oxide; Oxygen saturation; Pulmonary arteries; Pulmonary Embolism - complications; Pulmonary Embolism - diagnosis; Pulmonary Embolism - therapy; Pulmonary hypertension; Randomized Controlled Trials as Topic; Thromboembolism; Vascular medicine; Veins & arteries
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-072241

ObjectivesBalloon 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.Methods and analysisThis 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 weeks 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 weeks 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.Ethics and disseminationNational 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.Registration detailsJapan Registry of Clinical Trials: jRCT no. 041200052. ClinicalTrials.gov by National Library of Medicine Registry ID: NCT04600492.Trial registration number NCT04600492.