Using spironolactone to treat pulmonary arterial hypertension

A Pilot Study of the Effect of Spironolactone Therapy on Exercise Capacity and Endothelial Dysfunction in Pulmonary Arterial Hypertension

This study is testing if the medication spironolactone can help adults with pulmonary arterial hypertension by improving their blood vessel function and reducing inflammation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: prednisone
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT01712620 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of spironolactone, a medication known for its anti-inflammatory properties, in treating pulmonary arterial hypertension (PAH). The study will involve participants who are at least 18 years old and have been diagnosed with PAH, and it will last for 24 weeks. Participants will be randomly assigned to receive either spironolactone or a placebo, and their health will be monitored through physical exams and medical history assessments. The goal is to determine if early treatment with spironolactone can improve blood vessel function and reduce inflammation in patients with PAH.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older diagnosed with pulmonary arterial hypertension who are either not on any medical therapy or have been on stable therapy for at least four weeks.

Not a fit: Patients with severe pulmonary arterial hypertension who are already experiencing right heart failure may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of pulmonary arterial hypertension and enhance patient outcomes.

How similar studies have performed: While the use of spironolactone in PAH is not widely tested, its known benefits in improving endothelial function and reducing inflammation suggest potential for success.

Eligibility criteria

* INCLUSION CRITERIA:

  1. 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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  1. mean pulmonary artery pressure of \> 25 mmHg at rest,
  2. 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
  3. 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:

1. Patients with WHO Group 1 PH and evidence of right heart failure as defined by:

   1. NYHA/WHO class IV symptoms and
   2. Echocardiographic evidence of severe RV dysfunction and
   3. Clinical evidence of right heart failure which may include, but is not limited to elevated jugular venous pressure, ascites, and lower extremity edema
2. 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
3. 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)
4. Patients with WHO Group 1 pulmonary hypertension who have taken spironolactone or eplerenone within the last 30 days
5. Known or suspected allergy to spironolactone
6. Pregnant or breastfeeding women (all women of childbearing potential will be required to have a screening urine or blood pregnancy test)
7. Age \<18 years
8. Inability to provide informed written consent for participation in the study
9. Chronic kidney disease (an estimated glomerular filtration rate of \< 35 mL/min/1.73m\^2 of body surface area)
10. Serum potassium at the time of enrollment of \> 5 mEq/L
11. 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 \[For patients taking one of these medicines (ACE-Inhibitors or ARBs), the investigators agree to do due diligence by consulting a clinical center pharmacist and/or a standard pharmacy reference (i.e. Micromedex) to certify whether or not the patient is on a maximum dose of the drug.\]
12. 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:

1. Implanted cardiac pacemaker or defibrillator
2. Cochlear Implants
3. Ocular foreign body (e.g. metal shavings)
4. Embedded shrapnel fragments
5. Central nervous system aneurysm clips
6. Implanted neural stimulator
7. Any implanted device that is incompatible with MRI
8. 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
9. Subjects requiring monitored sedation for MRI studies
10. Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.)
11. 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:

1. History of severe allergic reaction to gadolinium contrast agents despite pre- medication with diphenhydramine and prednisone
2. Chronic kidney disease (an estimated glomerular filtration rate of \< 60 mL/min/1.73m\^2 of body surface area)

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Michael A Solomon, M.D. — National Institutes of Health Clinical Center (CC)
• Study coordinator: Grace M Graninger, R.N.

Conditions Pulmonary Arterial Hypertension; Magnetic Resonance Imaging