CTEPHPhase 3EPIPHANYNCT05140525
Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
A Phase 3 study testing Macitentan Tablets, Riociguat and balloon pulmonary angioplasty in people with CTEPH, run by Dr Sudarshan Rajagopal at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CTEPH
- What is being tested?
- Macitentan Tablets, Riociguat and balloon pulmonary angioplasty
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2025to 1 May 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
- 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).
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: 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.
Read the 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.
- Conditions
- CTEPH
- Being tested
- Macitentan Tablets, Riociguat, balloon pulmonary angioplasty
- Keywords
- Inoperable, Post-PTE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan TabletsDrug
Also called OPSUMIT
10 mg oral once daily
RiociguatDrug
Also called Adempas
1 mg to 2.5mg oral three times daily
balloon pulmonary angioplastyDevice
on hemodynamics and RV function (including advanced assessments of RV-PA coupling
| Study group | Role | What they receive |
|---|---|---|
| participants with inoperable CTEPH | Active comparator | subject with inoperable Chronic thromboembolic Pulmonary Hypertension Receives: 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 Receives: Drug: Macitentan Tablets; Drug: Riociguat; Device: balloon pulmonary angioplasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
6MWD will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.
Measured: 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.
NT-proBNP will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.
Measured: 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.
Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.
Measured: 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.
Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.
Measured: 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.
Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start27 Jan 2025
- Primary completion26 Mar 2026
- Study completion1 May 2026
Why it stopped: Sponsor Requested
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CTEPHStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr Sudarshan Rajagopal
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Pharmaceutica N.V., Belgium
- Responsible party
- Sponsor-investigator, Dr Sudarshan Rajagopal, Duke University
- Investigators
- Sudarshan Rajagopal, MD, PhD, Principal investigator, Duke Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05140525
- Sponsor's protocol ID
- Pro00105903
- Acronym
- EPIPHANY
- Status last verified
- Aug 2026
- First submitted
- 28 Oct 2021
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT05140525
- Acronym / sponsor ID
- EPIPHANY / Pro00105903
- Conditions
- CTEPH
- Keywords
- Inoperable, Post-PTE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Requested
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Dr Sudarshan RajagopalUniversity, hospital or other
- Collaborators
- Janssen Pharmaceutica N.V., Belgium
- Study start
- 27 Jan 2025 (actual)
- Primary completion
- 26 Mar 2026 (actual)
- Study completion
- 1 May 2026 (actual)
- First posted
- 1 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| participants with inoperable CTEPH | Active comparator | Drug: Macitentan Tablets, Drug: Riociguat, Device: balloon pulmonary angioplastysubject with inoperable Chronic thromboembolic Pulmonary Hypertension |
| post PTE residual CTEPH | Active comparator | Drug: Macitentan Tablets, Drug: Riociguat, Device: balloon pulmonary angioplastySubject with post pulmonary endarterectomy (PTE) residual Chronic Thromboembolic Pulmonary Hypertension |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
- Age ≥ 18 years' old
- Diagnosis of CTEPH
- Not a candidate for PTE
- Candidate for BPA based on suitable anatomy and disease burden
Key exclusion criteria (11 listed)
- Subjects presenting with any of the following will not be included in the trials:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Macitentan TabletsAlso: OPSUMIT10 mg oral once daily | Drug | participants with inoperable CTEPH, post PTE residual CTEPH |
| RiociguatAlso: Adempas1 mg to 2.5mg oral three times daily | Drug | participants with inoperable CTEPH, post PTE residual CTEPH |
| balloon pulmonary angioplastyon hemodynamics and RV function (including advanced assessments of RV-PA coupling | Device | participants with inoperable CTEPH, post PTE residual CTEPH |
Primary outcome
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.
5 secondary outcomes
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)
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)
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)
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)
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)
Results and safety
The study was stopped early (reason given: Sponsor Requested). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudarshan Rajagopal, MD, PhD principal investigator
Duke Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Macitentan Tablets, Riociguat and balloon pulmonary angioplasty in people with CTEPH, run by Dr Sudarshan Rajagopal at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Requested). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026; AzTrials last refreshed its copy on 8 Nov 2026.