Aldosterone activity during standard low-dose spironolactone

Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing

We will test whether taking 25 mg spironolactone blocks the effects of intravenous aldosterone on sodium handling in people with stable NYHA I–II heart failure.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Yale University (Academic / other)
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT07281014 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, double-dummy, placebo-controlled crossover trial where each participant receives four treatment periods: IV vehicle + oral placebo, IV vehicle + oral spironolactone 25 mg, IV aldosterone + oral placebo, and IV aldosterone + oral spironolactone 25 mg. Each period is separated by two weeks to allow spironolactone levels to reach steady state or wash out. The study measures changes in urine sodium-to-potassium ratio and sodium output after a standardized sodium chloride challenge as primary physiologic endpoints. Blood and urine biospecimens will also be collected to explore molecular and hormonal mechanisms underlying any observed effects.

Who should consider this trial

Good fit: Adults with chronic stable NYHA class I–II heart failure who have eGFR > 30 mL/min/1.73 m2, serum potassium 3.5–5.0 mEq/L, and are on stable heart-failure medications are the ideal candidates.

Not a fit: Patients with advanced or unstable heart failure, severe kidney dysfunction, a history of severe hyperkalemia, or those already on high-dose MRAs or other potassium-sparing diuretics are unlikely to benefit and are excluded.

Why it matters

Potential benefit: If successful, the results could reveal whether standard low-dose spironolactone leaves aldosterone activity unblocked and help guide better dosing or new treatments to reduce sodium retention in heart failure.

How similar studies have performed: Although MRAs like spironolactone are proven to improve outcomes in heart failure, the specific approach of using aldosterone infusion challenges during clinical MRA dosing is novel and has limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Chronic stable heart failure at optimal volume status. Inclusion will require participants to be NYHA class I or II.
2. eGFR \> 30 ml/min/1.73m2
3. Serum potassium ≤5.0 meq/L and ≥3.5 meq/L
4. Stable heart failure medications without need or expectation for changes during the 8-week study period
5. Free from heart failure decompensation for the preceding 60 day
6. Systolic blood pressure \>90 mmHg if not taking an MRA at screening. If patients are already taking an MRA at the time of screening a systolic blood pressure needs to be \>80 mmHg.

Exclusion Criteria:

1. Uncontrolled hypertension (SBP \> 160 mmHg)
2. Severe bladder dysfunction
3. Current MRA dose \> 50mg spironolactone or equivalent or non MRA potassium sparing diuretic such as amiloride
4. Contraindication to initiation or withdrawal of spironolactone per study procedures
5. History of severe hyperkalemia (K\>6.0 meq/l)
6. Brittle volume sensitive heart failure, recurrent flash pulmonary edema, restrictive cardiomyopathy or other pathology that would make aldosterone infusion high risk
7. Pregnant or breastfeeding
8. Women of childbearing potential that are not receiving a highly effective form of contraception. Females of childbearing potential must agree to use a highly effective method of birth control until 14 days after the last dose of study drug. The following are highly effective methods for this study:

   * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
   * Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
   * Intrauterine device (IUD)
   * Intrauterine hormone-releasing system (IUS)
   * Bilateral tubal occlusion
   * Vasectomized partner
   * Sexual abstinence

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey Testani, MD — Yale University
• Study coordinator: Veena Rao

Conditions Heart Failure; Spironolactone; Aldosterone