Riociguat for Chronic thromboembolic pulmonary hypertension

Inclusion criteria

• {"criterion_text":"- Age ≥18 years\n- CTEPH diagnosis in accordance with European guidelines applicable at the time of diagnosis\n- The availability of a documented post-BPA follow-up RHC performed within the last 3 months OR an anticipated post-BPA follow-up RHC with an mPAP <30 mmHg as determined by the treating physician's judgement\n- Riociguat monotherapy initiated prior to or within 2 weeks after the first BPA treatment\n- The capacity to adhere to the study visit schedule and to comprehend and comply with all protocol requirements\n- Ability to understand and provide written informed consent in the Dutch language"}

Exclusion criteria

• {"criterion_text":"- WHO functional class IV\n- Cardiac index <2.2l/min/m2\n- A post-BPA follow-up RHC within 3 months indicating an mPAP ≥ 30 mmHg\n- Patients who received any investigational medication within 1 month prior to the start of this study or who are scheduled to receive another investigational drug during the course of this study\n- A history of PEA prior to BPA\n- Presence of any other disease with a life expectancy of <1 year in the investigator’s opinion\n- History or suspicion of inability to cooperate adequately\n- Any condition that makes participation in this study inappropriate or unlikely to complete the trial period in the investigators opinion"}

Primary endpoints

• {"endpoint_text":"- Difference in mPAP between the riociguat discontinuation group and continuation group at the end of study follow-up (16 weeks)","definition_or_measurement_approach":"mPAP assessed at the end of study follow-up (16 weeks). The protocol references RHC follow-up assessments elsewhere; the endpoint specifies difference in mPAP at 16 weeks."}

Secondary endpoints

• {"endpoint_text":"- Efficacy endpoints: Differences between the intervention (discontinuation of riociguat) and control group (continuation of riociguat) at the end of the study follow-up for the following parameters in hierarchical order: NT-proBNP, 6MWD, PVR, Cardiac index","definition_or_measurement_approach":"NT-proBNP (biomarker assay), 6MWD (6-minute walk distance test), PVR and cardiac index (hemodynamic measurements as per protocol, typically from RHC)."}
• {"endpoint_text":"- Post hoc analysis of group differences in exercise capacity at the end of study follow-up (16 weeks): CPET variables (peak VO₂, load max, HR max, RER max, VE max, SpO₂ rest/max, O₂ pulse max, EqCO₂ at AT/max) and change in modified Borg dyspnoea scale","definition_or_measurement_approach":"Cardiopulmonary exercise testing (CPET) variables measured per CPET procedures; change in modified Borg dyspnoea scale as recorded at follow-up."}
• {"endpoint_text":"- Safety endpoints: group differences at end of study follow-up (16 weeks) in number of AEs and SAEs, proportion of patients with mPAP ≥38 mmHg at RHC, and proportion meeting clinical worsening criteria at week 8","definition_or_measurement_approach":"Adverse events and serious adverse events counted and compared; mPAP ≥38 mmHg assessed by RHC; clinical worsening criteria assessed at week 8 per protocol definitions."}
• {"endpoint_text":"- Feasibility of the strategy: 1) Is TTE sufficient to replace RHC at end of study follow-up (16 weeks)? Assessed via correlation between TTE and RHC (RVSP, TAPSE) and proportion of subjects with mPAP ≥38 mmHg missed by TTE at the end of study follow-up. 2) Is the discontinuation strategy feasible in practice? Assessed via subjects missed by clinical worsening criteria with mPAP >38mmHg at end of study follow-up, and subject satisfaction with the protocol.","definition_or_measurement_approach":"Correlation analyses between TTE and RHC measures (RVSP, TAPSE); proportion metrics for missed cases; subject satisfaction captured via questionnaires per protocol."}
• {"endpoint_text":"- Economic outcomes: difference in costs related to PH therapy and overall healthcare consumption, including frequency of visits to expert centers vs. local hospitals, travel distance for medical care, and number of emergency department visits.","definition_or_measurement_approach":"Prospective economic evaluation collecting healthcare utilization data, visit frequency, travel distance and ED visits to calculate cost differences."}
• {"endpoint_text":"- Patient-related outcomes: differences between discontinuation and continuation groups at end of study follow-up in WHO functional class and QoL scores (LPHQ, EQ-5D-5L). Also, number of predefined graded AEs including hypotension, dizziness, and diarrhoea.","definition_or_measurement_approach":"WHO functional class assessment, validated QoL instruments (LPHQ, EQ-5D-5L), and AE grading per protocol definitions."}

Netherlands

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

29-09-2025

Processing Time Days

17

Number Of Sites

2

Number Of Participants

74

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands