Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH

NCT05140525 | Recruiting Phase 3 FDA Drug

• 1 other identifier: Pro00105903
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this study is to determine the effects of combination medical therapy (Riociguat and Macitentan) and balloon pulmonary angioplasty (BPA) on hemodynamics and right ventricular (RV) function (including advanced assessments of RV-pulmonary artery (PA) coupling from invasive hemodynamics) in participants with inoperable or post-PTE residual CTEPH.

Conditions

CTEPH

Keywords

Inoperable; Post-PTE

Outcome Measures

Primary Outcomes (1)

• Change in end-systolic elastance (Ees) divided by arterial elastance (Ea) (Ees/Ea) at three time points: Baseline, Timepoint 1 and Timepoint 2.

  Ees is a measure of right ventricular (RV) - pulmonary arterial (PA) coupling, with a normal value of Ees/Ea \> 0.8 (dimensionless - no units). For subjects with Ees/Ea \> 0.8 at the start of the study, we will evaluate the absolute change in Ees/Ea between timepoints. For those with an Ees/Ea \< 0.8, we will also determine whether participants have an improvement to \> 0.8.

  Baseline (before starting all treatments); Timepoint 1 (after starting medical therapy; up to 6 months after baseline); Timepoint 2 (after balloon pulmonary angioplasty (BPA); up to 12 months after baseline)

Secondary Outcomes (5)

• Change in six-minute walk distance (6MWD) in meters.

  Baseline (before starting all treatments); Timepoint 1 (after starting medical therapy; up to 6 months after baseline); Timepoint 2 (after balloon pulmonary angioplasty (BPA); up to 12 months after baseline)

• Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) in picogram/milliliters.

  Baseline (before starting all treatments); Timepoint 1 (after starting medical therapy; up to 6 months after baseline); Timepoint 2 (after balloon pulmonary angioplasty (BPA); up to 12 months after baseline)

• Change in Cardiac index as measured by liters per minute per meters squared at right heart catheterization.

  Baseline (before starting all treatments); Timepoint 1 (after starting medical therapy; up to 6 months after baseline); Timepoint 2 (after balloon pulmonary angioplasty (BPA); up to 12 months after baseline)

• Change in pulmonary vascular resistance as measured by Wood units at right heart catheterization.

  Baseline (before starting all treatments); Timepoint 1 (after starting medical therapy; up to 6 months after baseline); Timepoint 2 (after balloon pulmonary angioplasty (BPA); up to 12 months after baseline)

• Change in right atrial pressure as measured by millimeters of mercury at right heart catheterization.

  Baseline (before starting all treatments); Timepoint 1 (after starting medical therapy; up to 6 months after baseline); Timepoint 2 (after balloon pulmonary angioplasty (BPA); up to 12 months after baseline)

Study Arms (2)

participants with inoperable CTEPH

ACTIVE COMPARATOR

subject with inoperable Chronic thromboembolic Pulmonary Hypertension

Drug: Macitentan Tablets; Drug: Riociguat; Device: balloon pulmonary angioplasty

post PTE residual CTEPH

ACTIVE COMPARATOR

Subject with post pulmonary endarterectomy (PTE) residual Chronic Thromboembolic Pulmonary Hypertension

Drug: Macitentan Tablets; Drug: Riociguat; Device: balloon pulmonary angioplasty

Interventions

Macitentan Tablets DRUG

10 mg oral once daily

Also known as: OPSUMIT

participants with inoperable CTEPH; post PTE residual CTEPH

Riociguat DRUG

1 mg to 2.5mg oral three times daily

Also known as: Adempas

participants with inoperable CTEPH; post PTE residual CTEPH

balloon pulmonary angioplasty DEVICE

on hemodynamics and RV function (including advanced assessments of RV-PA coupling

participants with inoperable CTEPH; post PTE residual CTEPH

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years' old
• Diagnosis of CTEPH
• Not a candidate for PTE
• Candidate for BPA based on suitable anatomy and disease burden
• Treatment-naïve (no CTEPH or pulmonary arterial hypertension (PAH)-specific medical therapies) with plans for initiation of CTEPH/PAH-specific medical therapy and treatment with BPA.
• Willing and able to give informed consent and adhere to visit/protocol schedules (Consent must be given before any study procedures are performed).

You may not qualify if:

• Subjects presenting with any of the following will not be included in the trials:
• Moderate to severe heart disease (LVEF \< 45% or severe LV Hypertrophy)
• Sarcoidosis
• Active cancer
• Sickle cell anemia
• Liver disease (Childs-Pugh class C)
• Prisoners
• Pregnant, planning pregnancy or lactating
• Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
• Contraindication to riociguat or macitentan
• Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements

Sponsors & Collaborators

• Dr Sudarshan Rajagopal: lead
• Janssen Pharmaceutica N.V., Belgium: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Interventions

macitentan; riociguat

Study Officials

• Sudarshan Rajagopal, MD, PhD

  Duke Health System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudia Salazar

CONTACT

+1 919 660 2026; claudia.salazar@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: December 1, 2021
• Study Start: January 27, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 21, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)