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The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02253394
Recruitment Status : Terminated (Low enrollment)
First Posted : October 1, 2014
Results First Posted : November 15, 2019
Last Update Posted : November 15, 2019
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Bradley Maron, MD, Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Ambrisentan plus Spironolactone Drug: Ambrisentan plus Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study (The CAPS-PAH Study)
Actual Study Start Date : September 2015
Actual Primary Completion Date : February 2018
Actual Study Completion Date : February 2018


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 Name: 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 Name: Letairis




Primary Outcome Measures :
  1. Effect of Combination Ambrisentan + Spironolactone on Peak Volume of Oxygen Consumption (pVO2) and Cardiac Output [ Time Frame: Up to average of 20 min ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02253394


Locations
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United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Gilead Sciences
Investigators
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Principal Investigator: Bradley Maron, MD Brigham and Women's Hospital
  Study Documents (Full-Text)

Documents provided by Bradley Maron, MD, Brigham and Women's Hospital:
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Responsible Party: Bradley Maron, MD, Instructor in Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02253394    
Other Study ID Numbers: CAPS_PAH
First Posted: October 1, 2014    Key Record Dates
Results First Posted: November 15, 2019
Last Update Posted: November 15, 2019
Last Verified: November 2019
Keywords provided by Bradley Maron, MD, Brigham and Women's Hospital:
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)
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Ambrisentan
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Antihypertensive Agents