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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03273257
Other study ID # PEA Bridging Study
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date August 17, 2018
Est. completion date May 5, 2020

Study information

Verified date May 2021
Source International CTEPH Association
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 14
Est. completion date May 5, 2020
Est. primary completion date May 5, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Riociguat
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
Placebo will be given analogue to riociguat with matching tablets.
Procedure:
Pulmonary endarterectomy
PEA will be performed at the end of medical treatment (Day 90)

Locations

Country Name City State
France Hopital de Bicêtre Paris
Germany Kerckhoff-Klinik GmbH Bad Nauheim
United Kingdom Papworth Hospital Cambridge
United States UC San Diego La Jolla California

Sponsors (1)

Lead Sponsor Collaborator
International CTEPH Association

Countries where clinical trial is conducted

United States,  France,  Germany,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in NT-proBNP From Baseline Until the End of Medical Treatment Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 90 days
Other Change in NT-proBNP From Baseline Until 6 Months Post-surgery Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Other Change in Cardiac Index From Baseline Until the End of Medical Treatment Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 90 days
Other Change in Cardiac Index From Baseline Until 6 Months Post-surgery Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Other Change in Mean Right Atrial Pressure From Baseline Until the End of Medical Treatment Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 90 days
Other Change in Mean Right Atrial Pressure From Baseline Until 6 Months Post-surgery Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Other Change in Mean Pulmonary Atrial Pressure From Baseline Until the End of Medical Treatment Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 90 days
Other Change in Mean Pulmonary Atrial Pressure From Baseline Until 6 Months Post-surgery Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Other Change in Pulmonary Artery Wedge Pressure From Baseline Until the End of Medical Treatment Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 90 days
Other Change in Pulmonary Artery Wedge Pressure From Baseline Until 6 Months Post-surgery Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Other Length of Hospital Stay for Pulmonary Endarterectomy Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study intraoperative
Other Length of Intensive Care Unit Stay for Pulmonary Endarterectomy Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study intraoperative
Other WHO Functional Class at the End of Medical Treatment Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 90 days
Other WHO Functional Class 6 Months Post Pulmonary Endarterectomy Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Other Need for PAH-targeted Therapy 6 Months Post-surgery Data are not reported for this exploratory endpoint because of limited sample size due to early termination of the study 270 days
Primary Change From Baseline in Pulmonary Vascular Resistance (PVR) to Immediately Before Pulmonary Endarterectomy (Pre-PEA) Pulmonary vascular resistance (PVR) will be assessed at baseline and immediately before pulmonary endarterectomy. The change in PVR will be assessed as percentage. 90 days
Secondary Change From Baseline in Pulmonary Vascular Resistance (PVR) to 6 Months Post Pulmonary Endarterectomy (PEA) Pulmonary vascular resistance (PVR) will be assessed at baseline and 6 months post pulmonary endarterectomy (PEA). The change in PVR will be assessed as percentage. 270 days
Secondary 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) All deaths occurring post-randomization until the last visit will be included. All PH-related hospitalizations except the in-hospital care during and after pulmonary endarterectomy (PEA) from randomization until 6 months after PEA will be included.
The worst value for World Health Organization (WHO) functional class after treatment will be used.
270 days
Secondary Intraoperative Circulatory Arrest Time Circulatory arrest time will be measured in minutes intraoperative
Secondary Number of Patients With Intraoperative Surgery-related Complications (Composite Endpoint) The occurrence of any of the following complications will be assessed:
Bleeding and/or blood loss >1 L in 12 hours
Airway bleed with need for extracorporeal membrane oxygenation
Any use of extracorporeal membrane oxygenation for respiratory or hemodynamic support, specified as veno-venous or veno-arterial
Prolonged ventilation >96 hours
Need for tracheostomy
Need for drainage of pericardial effusion
Neurological complications, ie, stroke, cerebral, subdural bleeding
Reintubation or noninvasive ventilation for reperfusion response
Hemoptysis requiring any intervention
Renal failure requiring dialysis
Wound infections
Pneumonia
Prolonged need for inotropic support (= 5 days)
intraoperative
Secondary Surgical Evaluation of Specimen: Stratification of Patients According to Ease of Dissection Plane Classed as easier than normal (1); normal (2); more difficult than normal (3) intraoperative
Secondary Surgical Evaluation of Specimen: Stratification of Patients According to Completeness of Disease Clearance Classed as better than expected (1); as expected (2); worse than expected (3) intraoperative
Secondary Surgical Evaluation of Specimen: Stratification of Patients According to Appearance of Clot and Vessel Wall Classed as more solid than usual (1); normal (2); more friable than usual (3) intraoperative
Secondary Number of Patients Who Died During the Course of the Study All deaths occurring during the whole course of the study 270 days
Secondary Patients Who Withdraw During the Randomized Treatment Phase Only withdrawals after randomization but before PEA will be included 90 days
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