Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy (PEA Bridging Study)
Condition: Chronic Thromboembolic Pulmonary Hypertension; CTEPH
MeSH terms: Hypertension, Pulmonary
Intervention: Riociguat; Placebo; Pulmonary endarterectomy
Intervention description: Riociguat will be initiated at 1 mg tid. The dosage will be increased by 0.5 mg at 2 week intervals based on tolerability as assessed by systolic blood pressure up to a maximum dose of 2.5 mg tid.
Downtitration to 0.5 mg tid is foreseen for patients with low optimal tolerability.; Placebo will be given analogue to riociguat with matching tablets.; PEA will be performed at the end of medical treatment (Day 90)
Intervention MeSH terms: Riociguat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Double-blind
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Pulmonary endarterectomy; PEA; Medical therapy

Summary:

      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.
    

Eligibility criteria:

        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