NCT01712620 · National Institutes of Health Clinical Center (CC)
Spironolactone for Pulmonary Arterial Hypertension
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Spironolactone
Initial dose, 25 mg (pink capsule) orally, daily. If well tolerated at 7-9 wks then increased to 50 mg (brown capsule) daily.
DRUG
Placebo
Initial dose, pink sugar capsule, daily. If well tolerated at 7-9 wks then changed to brown sugar capsule, daily.
Primary outcome measures
Change in placebo corrected 6-minute walk distance
Time frame: 6 months
Change in placebo corrected 6-minute walk distance.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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: <!-- -->
- 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. 2\) 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.
Exclusion criteria
- 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 OR Patients currently taking the maximum recommended dose of an ACE inhibitor or an angiotensin II receptor blocker \[For patients taking one of these medicines (ACE-Inhibitors or ARBs), the investigators agree to do due diligence by consulting a clinical center pharmacist and/or a standard pharmacy reference (i.e. Micromedex) to certify whether or not the patient is on a maximum dose of the drug.\]
- Women currently taking drospirenone-containing oral contraceptives The estimated glomerular filtration rate (eGFR) will be calculated using the IDMS-traceable Modification of Diet in Renal Disease (MDRD) equation and corrected for body surface area. eGFR = 175 x (serum creatinine in mg/dL)\^-1.154 x (age in years)\^-0.203 x \[1.212 if African-American\] x \[0.742 if female\] (http://www.nkdep.nih.gov/professionals/gfr\_calculators/idms\_con.htm) Exclusion Criteria for MRI These contraindications include but are not limited to the following devices or conditions:
- Implanted cardiac pacemaker or defibrillator
- Cochlear Implants
- Ocular foreign body (e.g. metal shavings)
- Embedded shrapnel fragments
- Central nervous system aneurysm clips
- Implanted neural stimulator
- Any implanted device that is incompatible with MRI
- Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and severe dyspnea at rest
- Subjects requiring monitored sedation for MRI studies
- Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.)
- Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination. EXCLUSION CRITERIA FOR GADOLINIUM BASED MRI STUDIES ONLY:
- History of severe allergic reaction to gadolinium contrast agents despite pre- medication with diphenhydramine and prednisone
- Chronic kidney disease (an estimated glomerular filtration rate of \< 60 mL/min/1.73m\^2 of body surface area)
Where
- Bethesda, Maryland
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Pennsylvania, University of Maryland, Baltimore, Medstar Health Research Institute, New England Medical Center, Tufts University School of Medicine
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 17, 2026 · Source of record for eligibility and locations