Back to results

The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

Primary Purpose

Pulmonary Arterial Hypertension

Status

Terminated

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Ambrisentan plus Spironolactone

Ambrisentan plus Placebo

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Arterial Hypertension (PAH), Ambrisentan, Spironolactone, Selective Endothelin A (ETA) inhibition, Aldosterone antagonism, Cardiac output (CO), Right ventricular (RV) function, Heart failure, Quality of life, Pro-inflammatory cytokine, Interleukin-6 (IL-6), Troponin-I, N-terminal pro-brain natriuretic peptide (NT-BNP), Collagen metabolism, N-terminal procollagen type I, Collagen III, Echocardiography, WHO Functional Class, Cardiopulmonary Exercise Test with Innocor, Peak oxygen consumption (pVO2), Liver function markers (AST/ALT), Renal function markers (creatinine and potassium)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Voluntarily gives informed consent to participate in the study.
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
Subject is 18 years of age or older at Screening.
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.
New York Heart Association Functional Class II or III
Stable therapy with ambrisentan 5 or 10 mg every day for > 90 days.
Baseline 6-Minute Walk Distance 50-450m

Exclusion Criteria:

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
Left ventricular ejection fraction < 50%
Pulmonary capillary wedge pressure > 16 mm Hg
Aortic valve disease
Ischemic heart disease
Systemic hypotension (SBP <90 mm Hg)
Co-existing treatment with other endothelin receptor antagonists or prostacyclin analogues
New York Heart Association Functional Class IV
Chronic thromboembolic pulmonary hypertension
Known or suspected pulmonary veno-occlusive disease
Serum creatinine >2.0 mg/dL in women, Serum creatinine >2.5 mg/dL in men
Baseline serum potassium >5.0 milliequivalent (mEq)/L
Participation in ongoing drug/intervention-based clinical trial
Pregnancy
Unable to provide consent

Sites / Locations

Brigham & Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

AMB + Spiro, Cardiopulmonary fitness

Placebo Cardiopulmonary fitness

Arm Description

Ambrisentan 5 or 10 mg every day (QD) Spironolactone 50 mg QD

Placebo mimics spironolactone 50 mg and will be taken QD

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02253394

First Posted

September 17, 2014

Last Updated

November 13, 2019

Sponsor

Brigham and Women's Hospital

Collaborators

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT02253394

Brief Title

The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Terminated

Why Stopped

Low enrollment

Study Start Date

September 2015 (Actual)

Primary Completion Date

February 2018 (Actual)

Study Completion Date

February 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

Gilead Sciences

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension (PAH), Ambrisentan, Spironolactone, Selective Endothelin A (ETA) inhibition, Aldosterone antagonism, Cardiac output (CO), Right ventricular (RV) function, Heart failure, Quality of life, Pro-inflammatory cytokine, Interleukin-6 (IL-6), Troponin-I, N-terminal pro-brain natriuretic peptide (NT-BNP), Collagen metabolism, N-terminal procollagen type I, Collagen III, Echocardiography, WHO Functional Class, Cardiopulmonary Exercise Test with Innocor, Peak oxygen consumption (pVO2), Liver function markers (AST/ALT), Renal function markers (creatinine and potassium)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AMB + Spiro, Cardiopulmonary fitness

Arm Type

Active Comparator

Arm Description

Ambrisentan 5 or 10 mg every day (QD) Spironolactone 50 mg QD

Arm Title

Placebo Cardiopulmonary fitness

Arm Type

Placebo Comparator

Arm Description

Placebo mimics spironolactone 50 mg and will be taken QD

Intervention Type

Drug

Intervention Name(s)

Ambrisentan plus Spironolactone

Other Intervention Name(s)

Letairis plus Aldactone

Intervention Description

Cardiopulmonary fitness

Intervention Type

Drug

Intervention Name(s)

Ambrisentan plus Placebo

Other Intervention Name(s)

Letairis

Intervention Description

Placebo is a sugar pill manufactured to resemble spironolactone 50 mg Cardiopulmonary fitness

Primary Outcome Measure Information:

Title

Effect of Combination Ambrisentan + Spironolactone on Peak Volume of Oxygen Consumption (pVO2) and Cardiac Output

Description

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.

Time Frame

Up to average of 20 min

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Voluntarily gives informed consent to participate in the study. 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 Subject is 18 years of age or older at Screening. 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. New York Heart Association Functional Class II or III Stable therapy with ambrisentan 5 or 10 mg every day for > 90 days. Baseline 6-Minute Walk Distance 50-450m Exclusion Criteria: 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 Left ventricular ejection fraction < 50% Pulmonary capillary wedge pressure > 16 mm Hg Aortic valve disease Ischemic heart disease Systemic hypotension (SBP <90 mm Hg) Co-existing treatment with other endothelin receptor antagonists or prostacyclin analogues New York Heart Association Functional Class IV Chronic thromboembolic pulmonary hypertension Known or suspected pulmonary veno-occlusive disease Serum creatinine >2.0 mg/dL in women, Serum creatinine >2.5 mg/dL in men Baseline serum potassium >5.0 milliequivalent (mEq)/L Participation in ongoing drug/intervention-based clinical trial Pregnancy Unable to provide consent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bradley Maron, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham & Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Learn more about this trial

The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

We'll reach out to this number within 24 hrs