The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

NCT02253394 | Terminated Phase 4 Results

• 1 other identifier: CAPS_PAH
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

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)

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

AMB + Spiro, Cardiopulmonary fitness

ACTIVE COMPARATOR

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

Drug: Ambrisentan plus Spironolactone

Placebo Cardiopulmonary fitness

PLACEBO COMPARATOR

Placebo mimics spironolactone 50 mg and will be taken QD

Drug: Ambrisentan plus Placebo

Interventions

Ambrisentan plus Spironolactone DRUG

Cardiopulmonary fitness

Also known as: Letairis plus Aldactone

AMB + Spiro, Cardiopulmonary fitness

Ambrisentan plus Placebo DRUG

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

Also known as: Letairis

Placebo Cardiopulmonary fitness

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Gilead Sciences: collaborator

Study Sites (1)

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Inhibition, Psychological; Heart Failure

Interventions

ambrisentan; Spironolactone

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Behavior; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Poor enrollment, study terminated early

Results Point of Contact

• Title: Dr. Bradley Maron
• Organization: Brigham and Women's Hospital

bmaron@bwh.harvard.edu

617-525-4857

Study Officials

• Bradley Maron, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in Medicine

Study Record Dates

• First Submitted: September 17, 2014
• First Posted: October 1, 2014
• Study Start: September 1, 2015
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: November 15, 2019
• Results First Posted: November 15, 2019

Record last verified: 2019-11

Locations

US (1)