EPIPHANY: Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than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
Arms and Interventions
| 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:
Drug: Riociguat
1 mg to 2.5mg oral three times daily
Other Names:
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:
Drug: Riociguat
1 mg to 2.5mg oral three times daily
Other Names:
Device: balloon pulmonary angioplasty
on hemodynamics and RV function (including advanced assessments of RV-PA coupling
|
Outcome Measures
Primary Outcome Measures
- Change in end-systolic elastance (Ees) divided by arterial elastance (Ea) (Ees/Ea) at three time points: Baseline, Timepoint 1 and Timepoint 2. [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 Outcome Measures
- 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)]
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. [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. [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. [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. [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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Dr Sudarshan Rajagopal
- Actelion
Investigators
- Principal Investigator: Sudarshan Rajagopal, MD, PhD, Duke Health System
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00105903