Riociguat Versus Balloon Pulmonary Angioplasty in Non-operable Chronic thromboEmbolic Pulmonary Hypertension

Inclusion Criteria

• •18 to 80 years of age at Visit 1
• •CTEPH patients considered as non-operable but eligible for balloon pulmonary angioplasty and riociguat by the multidisciplinary meeting, with pulmonary vascular resistance \> 320 dyn.sec.cm-5 and mean PAP \> 25 mmHg and PWP (Pulmonary capillary Wedge Pressure) ≤ 15 mmHg measured at least 3 months after start of full anticoagulation. If the patient is treated with new oral anticoagulants drugs, NOAC's, (rivaroxaban, apixaban, dabigatran), the treatment should be switched to Vitamin K antagonist (VKA).
• •The diagnosis of CTEPH must have been established based on 2 of the 3 following methods before study entry: ventilation-perfusion scan, pulmonary angiography, spiral-CT scan.
• •The diagnosis of inoperability must have been established based on spiral-CT scan and/or pulmonary angiography before study entry.
• •Unspecific treatments which may also be used for the treatment of pulmonary hypertension (PH) such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However treatment with anticoagulants must have been started at least 3 months before Visit 1.
• •Specific PH treatments (bosentan, ambrisentan, macitentan, sildenafil, tadalafil, epoprostenol, treprostinil, iloprost) are not permitted at Visit 1.
• •Patients who fulfill criteria for a supplemental long-term oxygen therapy (PaO2 \< 55 mmHg at rest) need to be supplied sufficiently before study entry. The amount of supplemental oxygen and the delivery method need to be stable for at least one month before Visit 1.
• •Right-heart catheterization results for the definite diagnosis of PH must not be older than 6 weeks at Visit 1 (will be considered as baseline values), must have been measured after at least 3 months of full anticoagulation, and must have been measured in the participating center under standardized conditions.
• •Women without childbearing potential defined as postmenopausal women aged 55 years or older, women with bilateral tubal ligation, women with bilateral ovarectomy, and women with hysterectomy can be included in the study. Women with childbearing potential can be included in the study only if a serological pregnancy test is negative and a combination of condoms with a safe and highly effective contraception method is used.
• •Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
• •Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.
• •Patients with significant interstitial lung disease on High-resolution computed tomography (HRCT)
• •Patients with hypersensitivity to riociguat or any of the excipients.
• •Treatment with :
• •* PDE-5 Inhibitors (eg Sildenafil or Tadalafil)
• •* NO donors (eg Nitrates)
• •Strong multi pathway cytochrome P450 (CYP) and P-glycoprotein (P-gp) / breast cancer resistance protein (BCRP) inhibitors such as azole antimycotics (e.g. ketoconazole, itraconazole) or HIV protease inhibitors (e.g. ritonavir)
• •Systolic blood pressure \<95mmHg
• •Patients with a history of life-threatening hemoptysis (\>100 mL in 24 h) or who have previously undergone bronchial arterial embolization for hemoptysis
• •Patients who could not remain in a supine position for at least 120 min for any reason.
• •Very distal CTEPH disease without stenosis, webs, or slits on CT scan and CTEPH disease with predominant complete occlusions of segmental or sub- segmental arteries (defined by the multidisciplinary meeting)