Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty
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:
1. WHO FC I or II
2. Pulmonary vascular resistance (PVR) \< 3 Wood units
3. 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
You may not be if
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
Clareo Health | Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty
