Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH

Inclusion Criteria

• •1. ≥18 years of age at time of inclusion.
• •2. Male and female patients with early pulmonary vascular disease, defined as either a) mean pulmonary arterial pressure (mPAP) ≥25 mmHg with pulmonary vascular resistance (PVR) ≥2 to \<3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg or b) mPAP 21-\<25 mmHg with PVR ≥2 WU, and PAWP ≤15 mmHg associated with connective tissue disease (CTD) or as idiopathic/heritable form (see Group I / Nice Clinical Classification of Pulmonary Hypertension) (acc. to Simonneau et al. 2019). Patients with rheumatoid arthritis or connective tissue disease of any kind, except systemic lupus erythematosus, may also be included. Patients in group b will be mainly enrolled as long as patients in group a are not defined as having pulmonary arterial hypertension according to European pulmonary hypertension guidelines.
• •3. Treatment naïve patients (with respect to PAH specific medication)
• •4. Unspecific treatments which may also be used for the treatment of pulmonary hypertension such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. Permitted are also treatments of the rheumatologic disease. However, these drugs must have been started at least 1 month before right heart catheterization.
• •5. Right-heart catheterization results must not be older than 1 month at Visit 1 (will be considered as baseline values, the time frame can be prolonged up to 6 months, if the patient has had no signs of clinical changes defined as \>10% change of 6MWD, WHO FC, \> 30% change in NT-proBNP) and must have been measured in the participating center under standardized conditions (refer to the study specific Swan Ganz catheterization manual). If the respective measurements have not been performed in context with the patient's regular diagnostic work up, they have to be performed as a part of the study during the pre-study phase (after the patient signed the informed consent).
• •6. Women without childbearing potential defined as postmenopausal women aged 55 years or older, women with bilateral tubal ligation, women with bilateral ovariectomy, and women with hysterectomy can be included in the study.
• •7. Women of childbearing potential can only be included in the study if all of the following applies (listed below):
• •1. Negative serum pregnancy test at screening and at study start (visit 1).
• •2. Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation. These tests should be performed by the patient at home.
• •3. Agreement to use a highly effective contraception method as specified from screening until at least 30 days after last dose of study medication.
• •8. Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
• •9. 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.