Evaluation of Riociguat Discontinuation Post-Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension: A Randomized Controlled Non-Inferiority Trial

The primary objective is to evaluate the safety and feasibility of discontinuing riociguat in patients diagnosed with chronic thromboembolic pulmonary hypertension who have achieved a mean pulmonary arterial pressure of less than 30 mmHg at least 6 months following balloon pulmonary angioplasty. Secondary objectives include:

• A prospective economic evaluation of riociguat discontinuation.
• Assessment of societal and patient-related benefits following the cessation of therapy.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) according to established European guidelines. Eligible participants are within specific age ranges identified by codes 3 and 4. Inclusion requirements necessitate that riociguat monotherapy was initiated either prior to or within two weeks following the initial balloon pulmonary angioplasty (BPA). Furthermore, participants must have achieved a mean pulmonary arterial pressure (mPAP) of less than 30 mmHg, as confirmed via right heart catheterization (RHC) performed within the last three months or anticipated via clinical judgment. The population must demonstrate the ability to adhere to the study schedule and provide informed consent in the Dutch language.

This Phase IV, randomized, controlled, non-inferiority trial evaluates the safety and feasibility of discontinuing riociguat in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) who have undergone balloon pulmonary angioplasty (BPA). The study design compares a discontinuation group against a continuation group. Participants must have achieved a mean pulmonary arterial pressure (mPAP) of less than 30 mmHg at least 6 months after the final BPA procedure. The research methodology involves a screening visit to confirm eligibility based on clinical guidelines and prior right heart catheterization (RHC) results. Following enrollment, the study includes a follow-up period of 16 weeks. The primary endpoint is the difference in mPAP between the two groups at the end-of-study visit. Secondary endpoints include assessments of NT-proBNP, 6-minute walk distance (6MWD), pulmonary vascular resistance (PVR), cardiac index, and various cardiopulmonary exercise testing (CPET) variables. Safety is monitored through the incidence of adverse events (AEs) and serious adverse events (SAEs). Clinical worsening criteria and transthoracic echocardiography (TTE) correlations are also evaluated to determine the feasibility of the discontinuation strategy.

The experimental medication consists of riociguat administered as Adempas 2.5 mg film-coated tablets. The prescribed dosage is 7.5 mg via the oral route.

The assessment of efficacy in patients with chronic thromboembolic pulmonary hypertension (CTEPH) focuses on the comparative analysis between the discontinuation and continuation of riociguat. The primary endpoint is the difference in mean pulmonary arterial pressure (mPAP) between the intervention and control groups at the 16-week follow-up. Secondary efficacy parameters, evaluated in hierarchical order at the end of the study follow-up, include N-terminal pro-brain natriuretic peptide (NT-proBNP), six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), and cardiac index.

Post hoc analyses at 16 weeks will examine differences in exercise capacity through cardiopulmonary exercise testing (CPET) variables, including peak VO₂, load max, HR max, RER max, VE max, SpO₂ rest/max, O₂ pulse max, and EqCO₂ at AT/max, alongside changes in the modified Borg dyspnoea scale. Additional patient-related outcomes assessed at the end of the study follow-up include WHO functional class and quality of life scores measured via the Living with Pulmonary Hypertension Questionnaire (LPHQ) and EQ-5D-5L.