Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy (PEA Bridging Study)

A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Prospective Study to Assess Efficacy of Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy With High Preoperative Pulmonary Vascular Resistance

This is a randomised, double-blind, placebo-controlled, multicentre, multinational, prospective study in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) prior to pulmonary endarterectomy (PEA) with high preoperative pulmonary vascular resistance (PVR). Patients will be randomised in a 1:1 ratio to receive riociguat or matching placebo for 3 months before undergoing PEA. The primary objective of this study is to assess the efficacy of riociguat on preoperative PVR compared to placebo in patients with operable CTEPH.

Inclusion Criteria:

• Is a male or nonpregnant and nonlactating female patient aged from 18 to 80 years, both inclusive
• Is diagnosed with operable CTEPH and anticipating symptomatic and/or prognostic benefit from PEA
• Has pulmonary vascular resistance (PVR) >800 dyn·s·cm-5
• Has undergone right heart catheterisation not more than 180 days before randomisation visit
• Has been treated with anticoagulants for at least 90 days before randomisation visit
• Has ability to swallow oral medication
• Has ability and willingness to participate and access the health facility
• Is capable of understanding the written informed consent and provides signed and witnessed written informed consent
• Female patient must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or male partner with vasectomy or complete abstinence)

Exclusion Criteria:

• Has unstable disease in need of urgent PEA surgery as determined by the treating physician
• Has known hypersensitivity, allergic, or adverse reactions to riociguat or any of the excipients comprising riociguat tablets.
• Has known active hepatitis A IgM (HAV-IgM), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV Ab)
• Is human immunodeficiency virus positive
• Has pulmonary veno-occlusive disease
• Has symptomatic hypotension
• Has symptomatic carotid disease
• Has significant coronary atherosclerotic disease in need of intervention
• Has severe left heart disease in need of intervention
• Has redo sternotomy
• Has received any background therapy for pulmonary arterial hypertension (PAH) in the preceding 30 days before randomisation visit including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, or prostanoids
• Is receiving nitrates, nitric oxide donors (e.g. amyl nitrite), ERAs, prostanoids, specific PDE5 inhibitors, nonspecific phosphodiesterase inhibitors (e.g. dipyridamole, theophylline)
• Is receiving strong cytochrome P450 (CYP) and P-glycoprotein/breast cancer resistance protein inhibitors
• Is receiving strong CYP3A inducers
• Has creatinine clearance <15 mL/min or on any form of dialysis
• Has severe hepatic impairment classified as Child-Pugh C
• Has received an investigational drug within the past 4 weeks before randomisation visit
• Is a lactating or pregnant (as demonstrated by a serum pregnancy test) woman, and not willing to take measures for not to become pregnant during the 3 months treatment study period and one month after the last dose of study drug administered
• Has smoked or used tobacco in any form, including snuff or chewing within 3 months prior to randomisation visit
• Has idiopathic interstitial pneumonitis