TerminatedInterventionalPhase 2Updated Jun 22, 2021
Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon... | NCT07644377 | Trialant
Not yet recruitingInterventionalPhase 3Updated Jun 12, 2026
Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty
Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty
ClinicalTrials.gov ID
NCT07644377
Lead Sponsor
Assistance Publique - Hôpitaux de ParisOTHER
Overall Status
Not yet recruiting
Study Type
Interventional
Phase
Phase 3
Enrollment
150Estimated
Last Update Posted
Jun 12, 2026Actual
Start Date
Oct 1, 2026Estimated
Primary Completion Date
Jan 31, 2031Estimated
Completion Date
Jan 31, 2031Estimated
Official Title
Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty
Brief Summary
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe complication of acute pulmonary embolism, characterized by persistent obstruction of the pulmonary arteries by organized thrombi and secondary microvasculopathy. International guidelines recommend a multimodal approach combining pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and medical treatment with riociguat, to address the full spectrum of CTEPH lesions. BPA and riociguat are recommended for symptomatic patients with inoperable CTEPH or persistent pulmonary hypertension after PEA. Riociguat is administered before BPA to reduce periprocedural complications by improving pulmonary hemodynamics. While this pre-BPA strategy is well established, post-BPA management is poorly studied, especially in patients achieving therapeutic goals, defined as WHO functional class I or II and near-normal resting pulmonary hemodynamics (70 to 80% of cases). In such cases, riociguat monotherapy is often continued long-term, despite its cost, burden, and potential side effects, which may negatively impact patients' quality of life. Retrospective single-center studies suggest that discontinuation of medical treatment does not lead to significant clinical deterioration. Therefore, we propose conducting a multicenter trial using a PROBE (prospective, randomized, open-label, blinded endpoint) design and a Bayesian approach to test if stopping riociguat monotherapy after successful BPA is associated with an acceptably low risk of clinical worsening over a follow-up period of at least one year compared to continuation. The trial will also assess the cost-effectiveness of riociguat discontinuation.
CTEPH
Discontinuation of riociguat
Ages Eligible for Study
Adult (18-64)Older Adult (65+)
Sexes Eligible for Study
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Signed informed consent and willingness to accept either discontinuation or continuation of riociguat monotherapy
2. Age ≥18 years
3. Diagnosis of inoperable CTEPH or persistent PH after PEA, with achievement of therapeutic goals following BPA, defined as:
WHO FC I or II
Pulmonary vascular resistance (PVR) < 3 Wood units
Mean pulmonary artery pressure (mPAP) < 30 mmHg
4. Treatment with riociguat monotherapy for ≥6 months, with stable dose for ≥3 months prior to enrollment
5. Last BPA session performed ≥6 months prior to enrollment
6. 6-minute walk distance (6MWD) ≥ 150 meters
7. For women of childbearing potential: highly effective contraception
Exclusion Criteria:
1. Background treatment with any PH-targeted therapy other than riociguat, (e.g., any endothelin receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE-5i), parenteral prostanoids, prostacyclin receptor agonist)
2. Post-capillary pulmonary hypertension, defined as pulmonary artery wedge pressure (PAWP) > 15 mmHg
3. Significant obstructive or restrictive lung disease, defined as:
FEV₁ < 60% predicted, with FEV₁/FVC < 65%
and/or total lung capacity (TLC) < 60% predicted
or known significant chronic lung disease on imaging (e.g., interstitial lung disease, emphysema)
4. Severe hepatic impairment, defined as:
Child-Pugh class B or C
and/or liver aminotransferase levels > 3× upper limit of normal (ULN)
6. Left heart failure with left ventricular ejection fraction (LVEF) < 40%
7. Ongoing or planned treatment with organic nitrates.
8. Concomitant treatment with strong cytochrome P450 3A4 (CYP3A4) inducers (e.g., rifabutin, rifampicin, carbamazepine, phenobarbital, phenytoin, St. John's wort)
9. Concomitant treatment with strong multi pathway P-glycoprotein (P-gp)/ breast cancer resistance protein (BCRP) inhibitors (e.g., lopinavir/ritonavir).
10. Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) or a moderate dual CYP3A4/CYP2C9 inhibitor (e.g., fluconazole, amiodarone) or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors.
11. History of life-threatening hemoptysis (>100 mL within 24 hours) or prior bronchial artery embolization for hemoptysis
12. Pregnancy, breastfeeding, or intention to become pregnant during the study period
13. Severe comorbidities or underlying conditions with an anticipated life expectancy < 12 months, including active malignancy with localized or metastatic disease
14. Lack of coverage by national health or social security systems
15. Alcohol abuse, as determined by the investigator
16. Any condition or factor likely to interfere with protocol compliance, in the opinion of the investigator
17. Patient under guardianship or curatorship
18. Participation in another interventional trial or being in the exclusion period following a previous research involving the human person