An open-label, prospective, single centre study of the effects of Riociguat on RIght VEntricular size and function in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension

Prior treatment

• Systolic blood pressure <95 mmHg (permitted and monitored closely if due to the study drug side effects).
• Severe proven or suspected coronary artery disease according to investigators opinion (patients with Canadian Cardiovascular Society Angina Classification class 2-4, and/or requiring nitrates, and/or myocardial infarction within the last 3 months before Visit 1).

Other illness

• Patients unable to perform a valid 6MWD test (e.g. orthopaedic disease, peripheral artery occlusive disease, which affects the patient´s ability to walk).
• Clinical evidence of symptomatic atherosclerotic disease (e.g. peripheral artery disease with reduced walking distance, history of stroke with persistent neurological deficit etc).
• Renal insufficiency (glomerular filtration rate <30 ml/min/m2 e.g. calculated based on the Cockcroft formula).
• Moderate to severe bronchial asthma or COPD (Forced Expiratory Volume <60% predicted) or severe restrictive lung disease (Total Lung Capacity < 70% predicted) and/or defined as if high resolution computed tomography shows >20% parenchymal lung disease.
• Clinical or radiological evidence of Pulmonary-Veno-Occlusive Disease (PVOD) or Pulmonary Capillary Haemangiomatosis (PCH) or PH and idiopathic interstitial pneumonia (PH-IIP)
• Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg and /or diastolic blood pressure >110 mmHg).

Lab values

• Clinically relevant hepatic dysfunction indicated by: − bilirubin >2 times upper limit normal − and / or hepatic transaminases >3 times upper limit normal − and / or signs of severe hepatic insufficiency (e.g. impaired albumin synthesis with an albumin < 32 g/l, hepatic encephalopathy > grade 1a: West Haven Criteria of Altered Mental Status In Hepatic Encephalopathy)
• Left heart failure with an ejection fraction less than 40%.

Other

• Severe congenital abnormalities of the lungs, thorax, and diaphragm.
• Hypertrophic obstructive cardiomyopathy.

• Patients with symptomatic PAH with a mean pulmonary artery pressure (mPAP) >20 mmHg and pulmonary vascular resistance (PVR) ≥2 Wood Units (WU), pulmonary arterial wedge pressure (PAWP) ≤15 mmHg (Group I / Nice Clinical Classification of Pulmonary Hypertension) OR [see next criterion]
• CTEPH (Group IV / Nice Clinical Classification of Pulmonary Hypertension) defined as one of the following options: − inoperable measured at least 3 months after start of full anticoagulation and mPAP >20 mmHg and PVR ≥2 WU, PAWP ≤15 mmHg or − persisting or recurrent PH after pulmonary endarterectomy (mPAP >20 mmHg and PVR ≥2 WU, PAWP ≤15 mmHg measured at least 6 months after surgery (acc. to Simonneau et al. 2018).
• Patients who are either treatment naïve (with respect to PAH specific medication) OR pre-treated with an endothelin receptor antagonist and/or a prostacyclin and/or a prostacyclin analogue (according to upfront combination treatment) or [see next criterion]
• pre-treated with phosphodiesterase type 5 inhibitor (PDE-5) with or without combination treatment with an endothelin receptor antagonist and/or prostacyclin analogue. Pre-treated patients need to be stable on PDE5i for at least two months prior to Visit 1. “Stable” is defined as no change in the type of PDE5i and the respective daily dose. PDE5i has to be stopped (sildenafil 24h, tadalafil 48h) before switching to riociguat. The switch from PDE5i to riociguat is due to clinical indication, particularly when the patient´s risk-profile remained in intermediate risk group despite adequate initial treatment including PDE5i (defined as at least 3 of the following parameters: clinical signs of progression, persistent WHO-FC III, 6MWD between 165-440m, peak V02 11-15ml/min/kg (35-65% predicted), NTproBNP 300-1400 ng/l, RA-area 18-26cm2,RAP 8-14mmHg, CI 2,0-2,4 l/min) or in case of PDE5i intolerance.
• RHC results must not be older than 6 months at screening