CTEPH
Conditions
Keywords
Inoperable, Post-PTE
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Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than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.
Interventions
DRUGMacitentan Tablets
10 mg oral once daily
DRUGRiociguat
1 mg to 2.5mg oral three times daily
on hemodynamics and RV function (including advanced assessments of RV-PA coupling
Sponsors
Janssen Pharmaceutica N.V., Belgium
Dr Sudarshan Rajagopal
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactClaudia Salazar
Outcome results
None listed