Clinical trial NCT05140525: Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
Official title: Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: CTEPH
Keywords: Inoperable
Post-PTE
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceutica N.V., Belgium
First posted: 2021-12-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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Detailed description: Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in end-systolic elastance (Ees) divided by arterial elastance (Ea) (Ees/Ea) at three time points: Baseline, Timepoint 1 and Timepoint 2.
timeFrame: 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:
measure: Change in six-minute walk distance (6MWD) in meters.
timeFrame: 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)
measure: Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) in picogram/milliliters.
timeFrame: 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)
measure: Change in Cardiac index as measured by liters per minute per meters squared at right heart catheterization.
timeFrame: 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)
measure: Change in pulmonary vascular resistance as measured by Wood units at right heart catheterization.
timeFrame: 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)
measure: Change in right atrial pressure as measured by millimeters of mercury at right heart catheterization.
timeFrame: 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)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke Health System
name: Sudarshan Rajagopal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: