Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing

Summary

The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy.

Eligibility

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

Conditions2

Locations1 site

Browse More Trials