Duke University Medical Center
Durham, North Carolina, 27710, United States
Location status: Recruiting
Location contact
David Ptashnik, MS
CONTACT
Sudarshan Rajagopal, MD, PhD
PRINCIPAL_INVESTIGATOR
Recruiting
NCT Number: NCT05140525
Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
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.
Recruiting
Interested in participating?
Request InfoKey information
Conditions
Age range
18 year and older
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 3
Primary location
About this study
Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than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.
Who can participate
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
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).
Exclusion criteria
- 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
Treatment and study plan
Macitentan Tablets
Drug10 mg oral once daily
Other names: OPSUMIT
Riociguat
Drug1 mg to 2.5mg oral three times daily
Other names: Adempas
balloon pulmonary angioplasty
Deviceon hemodynamics and RV function (including advanced assessments of RV-PA coupling
Primary outcomes
-
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.
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)
6MWD will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.
-
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.
-
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.
-
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.
-
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.
Study contacts
Contact information is provided by the study sponsor or research team.
Sponsors and collaborators
Lead sponsor
Dr Sudarshan Rajagopal
Other
Collaborators
- Janssen Pharmaceutica N.V., Belgium
Registry information
Official study title
Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension
Acronym: EPIPHANY
Important dates
- Study start
- 2025
- Primary completion
- 2026
- Study completion
- 2026
- First posted
- Dec 1, 2021
- Registry last updated
- Oct 21, 2025
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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