The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

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

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Ambrisentan plus Spironolactone; Drug: Ambrisentan plus Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AMB + Spiro, Cardiopulmonary fitness; Ambrisentan 5 or 10 mg every day (QD) Spironolactone 50 mg QD	Drug: Ambrisentan plus Spironolactone; Cardiopulmonary fitness; Other Names: Letairis plus Aldactone
Placebo Comparator: Placebo Cardiopulmonary fitness; Placebo mimics spironolactone 50 mg and will be taken QD	Drug: Ambrisentan plus Placebo; Placebo is a sugar pill manufactured to resemble spironolactone 50 mg Cardiopulmonary fitness; Other Names: Letairis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Bradley Maron, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: September 27, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Quality of life; Heart failure; Echocardiography; Spironolactone; Pulmonary Arterial Hypertension (PAH); Interleukin-6 (IL-6); Collagen metabolism; Ambrisentan; Selective Endothelin A (ETA) inhibition; Aldosterone antagonism; Cardiac output (CO); Right ventricular (RV) function; Pro-inflammatory cytokine; Troponin-I; N-terminal pro-brain natriuretic peptide (NT-BNP); N-terminal procollagen type I; Collagen III; WHO Functional Class; Cardiopulmonary Exercise Test with Innocor; Peak oxygen consumption (pVO2); Liver function markers (AST/ALT); Renal function markers (creatinine and potassium)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone; Ambrisentan
• Other Study ID Numbers: CAPS_PAH