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

NCT03273257 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PEA Bridging Study
• Study Type: interventional
• Target: 14
• Locations: 4 countries
• Sites: 4

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.

Conditions

Chronic Thromboembolic Pulmonary Hypertension; CTEPH

Keywords

Pulmonary endarterectomy; PEA; Medical therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Change From Baseline in Pulmonary Vascular Resistance (PVR) to 6 Months Post Pulmonary Endarterectomy (PEA)

  270 days

• 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

• 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 Ease of Dissection Plane

  intraoperative

Other Outcomes (15)

• Change in NT-proBNP From Baseline Until the End of Medical Treatment

  90 days

• Change in NT-proBNP From Baseline Until 6 Months Post-surgery

  270 days

• Change in Cardiac Index From Baseline Until the End of Medical Treatment

  90 days

Study Arms (2)

Riociguat

ACTIVE COMPARATOR

Patients will receive riociguat for 3 months followed by pulmonary endarterectomy.

Drug: Riociguat; Procedure: Pulmonary endarterectomy

Placebo

PLACEBO COMPARATOR

Patients will receive placebo for 3 months followed by pulmonary endarterectomy.

Drug: Placebo; Procedure: Pulmonary endarterectomy

Interventions

Riociguat DRUG

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.

Also known as: Adempas, BAY 63-2521

Riociguat

Placebo DRUG

Placebo will be given analogue to riociguat with matching tablets.

Placebo

Pulmonary endarterectomy PROCEDURE

PEA will be performed at the end of medical treatment (Day 90)

Also known as: PEA

Placebo; Riociguat

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• International CTEPH Association: lead

Study Sites (4)

UC San Diego

La Jolla, California, 92037-7892, United States

Location

Hopital de Bicêtre

Paris, France

Location

Kerckhoff-Klinik GmbH

Bad Nauheim, 61231, Germany

Location

Papworth Hospital

Cambridge, CB3 8RE, United Kingdom

Location

Related Links

• Website of the International CTEPH Association

MeSH Terms

Interventions

riociguat

Limitations and Caveats

The study was terminated after enrolling only 14 out of 88 planned patients, due to slower than expected recruitment and the additional limitations on clinical research imposed by the COVID-19 pandemic. No firm conclusions can be drawn based on the study data due to the limited sample size.

Results Point of Contact

• Title: David Jenkins, MD; Principal Investigator and ICA Board member
• Organization: Papworth Hospital NHS Foundation Trust

david.jenkins1@nhs.net

+44 1223 638000

Study Officials

• David Jenkins, MD

  Papworth Hospital NHS Foundation Trust, Cambridge, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2017
• First Posted: September 6, 2017
• Study Start: August 17, 2018
• Primary Completion: May 5, 2020
• Study Completion: May 5, 2020
• Last Updated: June 22, 2021
• Results First Posted: June 22, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); GB (1); US (1); FR (1)