The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

Pulmonary Arterial Hypertension Clinical Trial

Official title:

The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study (The CAPS-PAH Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02253394
• Other study ID #: CAPS_PAH
• Status: Terminated
• Phase: Phase 4
• Start date: September 2015
• Est. completion date: February 2018

Study information

• Verified date: November 2019
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out if spironolactone added to ambrisentan for Pulmonary Arterial Hypertension (PAH) will increase exercise capacity. We also want to find out if spironolactone and ambrisentan effect the cardiac output (amount of blood the heart pumps every minute), right ventricle function and quality of life.

Description:

A prospective, double blind, placebo-controlled clinical study involving 30 patients with World Health Organization (WHO) Group 1 pulmonary arterial hypertension being treated with ambrisentan randomized to receive placebo or spironolactone (50 mg/d) for 90 days using a cross-over trial design.

Eligible participants will be randomized to receive placebo or spironolactone (50 mg/d) for 90 days (Phase I). At the completion of Phase I, participants will undergo repeat end-point assessment followed by a 21-day drug washout period. Then, the 90 day crossover phase of the trial will occur (Phase II), in which participants randomized to placebo in Phase I will be treated with spironolactone (50 mg/d) in Phase II and vice versa. At the conclusion of Phase II, end-point measures are reassessed.

Spironolactone is a diuretic used in treatment of PAH patients. Spironolactone is usually added to medical treatment when doses of Lasix/Torsemide are increased and patients are at risk for hypokalemia.

Study procedures being done for this research study are the standard procedures performed on all PAH patients when they are in clinic for follow-up except for the Cardiopulmonary Exercise Test (CPET) with Innocor.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Voluntarily gives informed consent to participate in the study.

2. Right heart catheterization demonstrating conventional mean pulmonary artery pressure (mPAP) >25, pulmonary vascular resistance (PVR) >3.0 Wood Units, pulmonary capillary wedge pressure (PCWP) <16 mmHg within two years of enrollment

3. Subject is 18 years of age or older at Screening.

4. Diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with Connective Tissue Disease (CTD), PAH associated with repaired/unrepaired congenital systemic-to-pulmonary shunt, Portopulmonary hypertension or PAH associated with HIV infection.

5. New York Heart Association Functional Class II or III

6. Stable therapy with ambrisentan 5 or 10 mg every day for > 90 days.

7. Baseline 6-Minute Walk Distance 50-450m

Exclusion Criteria:

1. Substantial Primary Lung disease

• forced expiratory volume at one second (FEV-1)/forced vital capacity (FVC) <0.6 and FEV-1 <70% predicted

• diffusing capacity of lung for carbon monoxide (DLCO) <30% predicted

• Pulmonary fibrosis

2. Left ventricular ejection fraction < 50%

3. Pulmonary capillary wedge pressure > 16 mm Hg

4. Aortic valve disease

5. Ischemic heart disease

6. Systemic hypotension (SBP <90 mm Hg)

7. Co-existing treatment with other endothelin receptor antagonists or prostacyclin analogues

8. New York Heart Association Functional Class IV

9. Chronic thromboembolic pulmonary hypertension

10. Known or suspected pulmonary veno-occlusive disease

11. Serum creatinine >2.0 mg/dL in women, Serum creatinine >2.5 mg/dL in men

12. Baseline serum potassium >5.0 milliequivalent (mEq)/L

13. Participation in ongoing drug/intervention-based clinical trial

14. Pregnancy

15. Unable to provide consent

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Ambrisentan plus Spironolactone
Cardiopulmonary fitness
• Ambrisentan plus Placebo
Placebo is a sugar pill manufactured to resemble spironolactone 50 mg Cardiopulmonary fitness

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of Combination Ambrisentan + Spironolactone on Peak Volume of Oxygen Consumption (pVO2) and Cardiac Output	Study the effect of combination ambrisentan (5-10 mg/d) + spironolactone (50 mg/d) on pVO2 and cardiac output. The pVO2 refers to a measure of general physical fitness measured during exercise.	Up to average of 20 min