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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03273257
• Date of registration: 25/08/2017
• Prospective Registration: Yes
• Primary sponsor: International CTEPH Association
• Public title: Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy (PEA Bridging Study)
• Scientific title: 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
• Date of first enrolment: August 17, 2018
• Target sample size: 14
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03273257
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

France, Germany, United Kingdom, United States

Contacts

• Name: David Jenkins, MD
• Affiliation: Papworth Hospital NHS Foundation Trust, Cambridge, UK

Key inclusion & exclusion 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 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



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Thromboembolic Pulmonary Hypertension

CTEPH

Intervention(s)

Drug: Placebo

Drug: Riociguat

Procedure: Pulmonary endarterectomy

Primary Outcome(s)

Change from baseline in pulmonary vascular resistance (PVR) to immediately before pulmonary endarterectomy (pre-PEA) [Time Frame: 90 days]

Secondary Outcome(s)

Change from baseline in pulmonary vascular resistance (PVR) to 6 months post pulmonary endarterectomy (PEA) [Time Frame: 270 days]

Frequency of withdrawal during randomised treatment phase [Time Frame: 90 days]

Surgical evaluation of specimen: completeness of disease clearance [Time Frame: intraoperative]

Frequency of intraoperative surgery-related complications (composite endpoint) [Time Frame: intraoperative]

Number of patients with either all-cause death, PH-related hospitalisation, need for PAH-targeted therapy or WHO functional class unchanged or worse between randomisation and 6 months post pulmonary endarterectomy (composite endpoint) [Time Frame: 270 days]

Surgical evaluation of specimen: appearance of clot and vessel wall [Time Frame: intraoperative]

Surgical evaluation of specimen: ease of dissection plane [Time Frame: intraoperative]

Frequency of all-cause death [Time Frame: 270 days]

Intraoperative circulatory arrest time [Time Frame: intraoperative]

Secondary ID(s)

PEA Bridging Study

Source(s) of Monetary Support

Please refer to primary and secondary sponsors