Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH

CTEPH Clinical Trial

— EPIPHANY  

Official title:

Effects of Combination Medical Therapy Followed by Balloon Pulmonary Angioplasty on Right Ventricular-PA Coupling and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05140525
• Other study ID #: Pro00105903
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 31, 2024
• Est. completion date: July 31, 2024

Study information

• Verified date: March 2024
• Source: Duke University
• Contact: David Ptashnik, MS
• Phone: 9196682642
• Email: david.ptashnik[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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Recent presented but unpublished results from trials of BPA vs riociguat for inoperable CTEPH (NCT02634203) have demonstrated that BPA provides a more significant hemodynamic benefit than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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• CTEPH

Intervention

Drug:
• Macitentan Tablets
10 mg oral once daily
• Riociguat
1 mg to 2.5mg oral three times daily

Device:
• balloon pulmonary angioplasty
on hemodynamics and RV function (including advanced assessments of RV-PA coupling

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Dr Sudarshan Rajagopal	Actelion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in end-systolic elastance (Ees) divided by arterial elastance (Ea) (Ees/Ea) at three time points: Baseline, Timepoint 1 and Timepoint 2.	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.	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	Change in six-minute walk distance (6MWD) in meters.	6MWD will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.	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	Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) in picogram/milliliters.	NT-proBNP will be determined at baseline, timepoint 1 and timepoint 2. Absolute change between these timepoints will be determined.	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	Change in Cardiac index as measured by liters per minute per meters squared at right heart catheterization.	Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.	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	Change in pulmonary vascular resistance as measured by Wood units at right heart catheterization.	Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.	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	Change in right atrial pressure as measured by millimeters of mercury at right heart catheterization.	Right heart catheterization will be performed at baseline, timepoint 1 and timepoint 2 and parameters determined. Absolute change between these timepoints will be determined.	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)