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

September 1, 2026 updated by: Dr Sudarshan Rajagopal

Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than medical therapy. The investigators hypothesize that participants who are treated with upfront combination medical therapy followed by BPA will have significant improvements in their hemodynamics and RV-PA coupling that can be monitored over time.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

  1. Age ≥ 18 years' old
  2. Diagnosis of CTEPH
  3. Not a candidate for PTE
  4. Candidate for BPA based on suitable anatomy and disease burden
  5. 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.
  6. Willing and able to give informed consent and adhere to visit/protocol schedules (Consent must be given before any study procedures are performed).

Exclusion Criteria:

  • Subjects presenting with any of the following will not be included in the trials:

    1. Moderate to severe heart disease (LVEF < 45% or severe LV Hypertrophy)
    2. Sarcoidosis
    3. Active cancer
    4. Sickle cell anemia
    5. Liver disease (Childs-Pugh class C)
    6. Prisoners
    7. Pregnant, planning pregnancy or lactating
    8. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
    9. Contraindication to riociguat or macitentan
    10. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: participants with inoperable CTEPH
subject with inoperable Chronic thromboembolic Pulmonary Hypertension
Drug: Macitentan Tablets
10 mg oral once daily
Other Names:
  • OPSUMIT
Drug: Riociguat
1 mg to 2.5mg oral three times daily
Other Names:
  • Adempas
Device: balloon pulmonary angioplasty
on hemodynamics and RV function (including advanced assessments of RV-PA coupling
Active Comparator: post PTE residual CTEPH
Subject with post pulmonary endarterectomy (PTE) residual Chronic Thromboembolic Pulmonary Hypertension
Drug: Macitentan Tablets
10 mg oral once daily
Other Names:
  • OPSUMIT
Drug: Riociguat
1 mg to 2.5mg oral three times daily
Other Names:
  • Adempas
Device: balloon pulmonary angioplasty
on hemodynamics and RV function (including advanced assessments of RV-PA coupling

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in end-systolic elastance (Ees) divided by arterial elastance (Ea) (Ees/Ea) at three time points: Baseline, Timepoint 1 and Timepoint 2.
Time Frame: 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)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in six-minute walk distance (6MWD) in meters.
Time Frame: 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)
6MWD will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.
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.
Time Frame: 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)
NT-proBNP will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.
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.
Time Frame: 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)
Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.
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.
Time Frame: 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)
Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.
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.
Time Frame: 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)
Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr Sudarshan Rajagopal

Collaborators

Janssen Pharmaceutica N.V., Belgium

Investigators

  • Principal Investigator: Sudarshan Rajagopal, MD, PhD, Duke Health System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 27, 2025

Primary Completion (Actual)

March 26, 2026

Study Completion (Actual)

May 1, 2026

Study Registration Dates

First Submitted

October 28, 2021

First Submitted That Met QC Criteria

November 17, 2021

First Posted (Actual)

December 1, 2021

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00105903

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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