Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
- Conditions
- CTEPH
- Interventions
- Registration Number
- NCT05140525
- Lead Sponsor
- Dr Sudarshan Rajagopal
- 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.
- 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Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
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).
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description participants with inoperable CTEPH Macitentan Tablets subject with inoperable Chronic thromboembolic Pulmonary Hypertension participants with inoperable CTEPH Riociguat subject with inoperable Chronic thromboembolic Pulmonary Hypertension participants with inoperable CTEPH balloon pulmonary angioplasty subject with inoperable Chronic thromboembolic Pulmonary Hypertension post PTE residual CTEPH Macitentan Tablets Subject with post pulmonary endarterectomy (PTE) residual Chronic Thromboembolic Pulmonary Hypertension post PTE residual CTEPH Riociguat Subject with post pulmonary endarterectomy (PTE) residual Chronic Thromboembolic Pulmonary Hypertension post PTE residual CTEPH balloon pulmonary angioplasty Subject with post pulmonary endarterectomy (PTE) residual Chronic Thromboembolic Pulmonary Hypertension
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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 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.
Trial Locations
- Locations (1)
Duke University Medical Center
🇺🇸Durham, North Carolina, United States