Spironolactone for Pulmonary Arterial Hypertension

NCT01712620 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 12021112-CC-0211
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- High blood pressure in the lungs, known as pulmonary arterial hypertension (PAH), is a rare disorder. In spite of recent advances in treatment, the death rate remains unacceptably high. Lung blood vessel function can be harmed by progressive injuries, such as inflammation, leading to worsening of the disease. A drug called spironolactone has been known to improve blood vessel function and reduce inflammation. Some people with PAH take spironolactone to help treat fluid retention. However, its effect on inflammation and blood vessel function in patients with PAH is not known. Researchers want to see if spironolactone can help these conditions in people with PAH. Objectives: \- To test the effectiveness of spironolactone in treating pulmonary arterial hypertension. Eligibility: \- Individuals at least 18 years of age with pulmonary arterial hypertension. Design:

• This study will last for 24 weeks. Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
• Participants will take either spironolactone or a placebo. They will take their study drug or placebo for 7 weeks. Treatment will be monitored with regular blood tests.
• In Week 8, participants who have had no reaction to the treatment will receive a higher dose of the drug or placebo.
• In Week 12, participants will have a study visit with heart and lung function tests. They will also have a 6-minute walk test, and provide blood and urine samples.
• After additional study visits for blood samples, participants will have a final visit in Week 24. The tests from Week 12 will be repeated at this visit.

Conditions

Pulmonary Arterial Hypertension

Keywords

Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Change in placebo corrected 6-minute walk distance

  Change in placebo corrected 6-minute walk distance.

  6 months

Secondary Outcomes (4)

• Change in placebo corrected VO2 max

  6 months

• Change in right ventricular function

  6 months

• Biomarkers of vascular inflammation

  6 months

• Rate of study drug discontinuation due to hyperkalemia, renal insufficiency, or other side effects such as breast pain and gynecomastia

  6 months

Study Arms (2)

Group A

EXPERIMENTAL

Spironolactone

Drug: Spironolactone

Group B

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Initial dose, pink sugar capsule, daily. If well tolerated at 7-9 wks then changed to brown sugar capsule, daily.

Group B

Spironolactone DRUG

Initial dose, 25 mg (pink capsule) orally, daily. If well tolerated at 7-9 wks then increased to 50 mg (brown capsule) daily.

Group A

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• WHO Group 1 PH patients on either no medical therapy or stable medical therapy for at least the past 4 weeks (defined as no new PAH-specific therapy, no change in the dose of current PAH-specific therapy and no change in NYHA/WHO functional classification within the past 4 weeks) are eligible. The following parameters on RHC are required to meet the hemodynamic definition of PAH:
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• mean pulmonary artery pressure of \> 25 mmHg at rest,
• pulmonary capillary wedge pressure of less than or equal to 15 mmHg (or a left ventricular end-diastolic pressure of less than or equal to 12 mmHg) and
• pulmonary vascular resistance of \> 3 Wood units (240 dyn.s.cm\^-5).
• If clinically indicated at the time of enrollment, then a RHC will be performed at the NIH Clinical Center upon study entry under a procedural consent.
• \) Females who are able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to and for the duration of study participation.

You may not qualify if:

• Patients with WHO Group 1 PH and evidence of right heart failure as defined by:
• NYHA/WHO class IV symptoms and
• Echocardiographic evidence of severe RV dysfunction and
• Clinical evidence of right heart failure which may include, but is not limited to elevated jugular venous pressure, ascites, and lower extremity edema
• Patients with WHO Group 1 pulmonary hypertension and a prior diagnosis of cirrhosis with portal hypertension as evidenced by a history of ascites, hepatic encephalopathy and/or varices prior to enrollment
• Patients with WHO Group 1 pulmonary hypertension and evidence of active infection, (HIV patients with two consecutive viral loads of \< 500 on their most recent determinations within the past 12 months will be considered to have inactive infection)
• Patients with WHO Group 1 pulmonary hypertension who have taken spironolactone or eplerenone within the last 30 days
• Known or suspected allergy to spironolactone
• Pregnant or breastfeeding women (all women of childbearing potential will be required to have a screening urine or blood pregnancy test)
• Age \<18 years
• Inability to provide informed written consent for participation in the study
• Chronic kidney disease (an estimated glomerular filtration rate of \< 35 mL/min/1.73m\^2 of body surface area)
• Serum potassium at the time of enrollment of \> 5 mEq/L
• Concurrent use of an ACE inhibitor and angiotensin II receptor blocker
• Patients currently taking the maximum recommended dose of an ACE inhibitor or an angiotensin II receptor blocker \[For patients taking one of these medicines (ACE-Inhibitors or ARBs), the investigators agree to do due diligence by consulting a clinical center pharmacist and/or a standard pharmacy reference (i.e. Micromedex) to certify whether or not the patient is on a maximum dose of the drug.\]

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Pennsylvania: collaborator
• University of Maryland, Baltimore: collaborator
• Medstar Health Research Institute: collaborator
• New England Medical Center, Tufts University School of Medicine: collaborator
• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Elinoff JM, Rame JE, Forfia PR, Hall MK, Sun J, Gharib AM, Abd-Elmoniem K, Graninger G, Harper B, Danner RL, Solomon MA. A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial. Trials. 2013 Apr 2;14:91. doi: 10.1186/1745-6215-14-91.

  PMID: 23547564 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael A Solomon, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Grace M Graninger, R.N.

CONTACT

(301) 496-9320; ggraninger@cc.nih.gov

Michael A Solomon, M.D.

CONTACT

(301) 496-9320; msolomon@cc.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2012
• First Posted: October 23, 2012
• Study Start: January 10, 2014
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04-02

Locations

US (1)