STOP-RIO: A randomized controlled non-inferiority trial to test the safety of discontinuation of riociguat after balloon pulmonary angioplasty in Chronic Thrombo-embolic Pulmonary Hypertension

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

28 Oct 2025 → ongoing

Decision date (initial)

2025-09-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Therapy

To assess the safety and feasibility of stopping riociguat in CTEPH patients who reach an mPAP < 30 mmHg at least 6 months after the last BPA.

Secondary objectives 2

1. To perform a prospective economic evaluation of riociguat discontinuation.
2. To assess the societal and patient-related benefits of riociguat discontinuation.

Conditions and MedDRA coding

Chronic thromboembolic pulmonary hypertension (CTEPH)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18 years
2. CTEPH diagnosis in accordance with European guidelines applicable at the time of diagnosis
3. 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
4. Riociguat monotherapy initiated prior to or within 2 weeks after the first BPA treatment
5. The capacity to adhere to the study visit schedule and to comprehend and comply with all protocol requirements
6. Ability to understand and provide written informed consent in the Dutch language

Exclusion criteria 8

1. WHO functional class IV
2. Cardiac index <2.2l/min/m2
3. A post-BPA follow-up RHC within 3 months indicating an mPAP ≥ 30 mmHg
4. 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
5. A history of PEA prior to BPA
6. Presence of any other disease with a life expectancy of <1 year in the investigator’s opinion
7. History or suspicion of inability to cooperate adequately
8. Any condition that makes participation in this study inappropriate or unlikely to complete the trial period in the investigators opinion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in mPAP between the riociguat discontinuation group and continuation group at the end of study follow-up (16 weeks)

Secondary endpoints 6

1. 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
2. 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
3. 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
4. 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.
5. 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.
6. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Jurjan Aman

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Jurjan Aman

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications