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
Overview
- Phase
- Phase 2
- Intervention
- Riociguat
- Conditions
- Chronic Thromboembolic Pulmonary Hypertension
- Sponsor
- International CTEPH Association
- Enrollment
- 14
- Locations
- 4
- Primary Endpoint
- Change From Baseline in Pulmonary Vascular Resistance (PVR) to Immediately Before Pulmonary Endarterectomy (Pre-PEA)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief 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.
Investigators
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
Arms & Interventions
Riociguat
Patients will receive riociguat for 3 months followed by pulmonary endarterectomy.
Intervention: Riociguat
Riociguat
Patients will receive riociguat for 3 months followed by pulmonary endarterectomy.
Intervention: Pulmonary endarterectomy
Placebo
Patients will receive placebo for 3 months followed by pulmonary endarterectomy.
Intervention: Placebo
Placebo
Patients will receive placebo for 3 months followed by pulmonary endarterectomy.
Intervention: Pulmonary endarterectomy
Outcomes
Primary Outcomes
Change From Baseline in Pulmonary Vascular Resistance (PVR) to Immediately Before Pulmonary Endarterectomy (Pre-PEA)
Time Frame: 90 days
Pulmonary vascular resistance (PVR) will be assessed at baseline and immediately before pulmonary endarterectomy. The change in PVR will be assessed as percentage.
Secondary Outcomes
- Number of Patients With Either All-cause Death, PH-related Hospitalization, Need for PAH-targeted Therapy or WHO Functional Class Unchanged or Worse Between Randomization and 6 Months Post Pulmonary Endarterectomy (Composite Endpoint)(270 days)
- Surgical Evaluation of Specimen: Stratification of Patients According to Ease of Dissection Plane(intraoperative)
- Surgical Evaluation of Specimen: Stratification of Patients According to Completeness of Disease Clearance(intraoperative)
- Change From Baseline in Pulmonary Vascular Resistance (PVR) to 6 Months Post Pulmonary Endarterectomy (PEA)(270 days)
- Intraoperative Circulatory Arrest Time(intraoperative)
- Number of Patients With Intraoperative Surgery-related Complications (Composite Endpoint)(intraoperative)
- Surgical Evaluation of Specimen: Stratification of Patients According to Appearance of Clot and Vessel Wall(intraoperative)
- Number of Patients Who Died During the Course of the Study(270 days)
- Patients Who Withdraw During the Randomized Treatment Phase(90 days)