Heart FailurePhase 4NCT07281014
Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing
A Phase 4 study testing Spironolactone 25mg and Aldosterone in people with Heart Failure, run by Yale University at 1 site in United States.
Trial summary
The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Spironolactone 25mg and Aldosterone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2026to Aug 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic stable heart failure at optimal volume status. Inclusion will require participants to be NYHA class I or II.
- eGFR > 30 ml/min/1.73m2
- Serum potassium ≤5.0 meq/L and ≥3.5 meq/L
- Stable heart failure medications without need or expectation for changes during the 8-week study period
- Free from heart failure decompensation for the preceding 60 day
- 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.
Who cannot join
- Uncontrolled hypertension (SBP > 160 mmHg)
- Severe bladder dysfunction
- Current MRA dose > 50mg spironolactone or equivalent or non MRA potassium sparing diuretic such as amiloride
- Contraindication to initiation or withdrawal of spironolactone per study procedures
- History of severe hyperkalemia (K>6.0 meq/l)
- Brittle volume sensitive heart failure, recurrent flash pulmonary edema, restrictive cardiomyopathy or other pathology that would make aldosterone infusion high risk
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- Pregnant or breastfeeding
- 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
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy.
Read the detailed description
This is a randomized, double blind, double dummy, placebo-controlled, crossover study where aldosterone will be infused intravenously (IV) with and without guideline recommended low dose oral mineralocorticoid receptor antagonists therapy. Participants will receive, in a randomized order, 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone. Each crossover period will be separated by 2 weeks to allow for steady state blood level of spironolactone and metabolites to be reached (or complete washout from prior spironolactone). The broad study design will be designed around evaluation of change in urine sodium to potassium ratio, sodium output following a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses.
- Conditions
- Heart Failure
- Being tested
- Placebo, Spironolactone 25mg, Aldosterone
- Keywords
- Spironolactone, Aldosterone
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
- IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
Spironolactone 25mgDrug
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
- IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
AldosteroneDrug
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
- IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
| Study group | Role | What they receive |
|---|---|---|
| Placebo/placebo | Placebo comparator | This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. Receives: Drug: Placebo |
| Placebo/Sprironolactone | Active comparator | This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. Receives: Drug: Placebo; Drug: Spironolactone 25mg |
| placebo/aldosterone | Active comparator | This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. Receives: Drug: Placebo; Drug: Aldosterone |
| aldosterone/spironolactone | Active comparator | This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. Receives: Drug: Spironolactone 25mg; Drug: Aldosterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in urine sodium to potassium ratio
Change in sodium to potassium ratio between aldosterone vs vehicle infusion during the spironolactone vs. placebo arms.
Measured: 59 days
Secondary outcomes (2)
Urine Sodium output following saline load
Effect of MRA and aldosterone infusion on natriuresis following a saline load
Measured: 59 days
Natriuretic effect of adjuvant to loop diuretic therapy
Effect of MRA and aldosterone infusion on natriuresis following IV bumetanide challenge
Measured: 59 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start27 Jan 2026
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Jeffrey Testani, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07281014
- Sponsor's protocol ID
- 2000040063
- Status last verified
- Aug 2026
- First submitted
- 3 Dec 2025
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing
- ClinicalTrials.gov ID
- NCT07281014
- Acronym / sponsor ID
- 2000040063
- Conditions
- Heart Failure
- Keywords
- Spironolactone, Aldosterone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 27 Jan 2026 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 15 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy.
Detailed description
This is a randomized, double blind, double dummy, placebo-controlled, crossover study where aldosterone will be infused intravenously (IV) with and without guideline recommended low dose oral mineralocorticoid receptor antagonists therapy. Participants will receive, in a randomized order, 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone. Each crossover period will be separated by 2 weeks to allow for steady state blood level of spironolactone and metabolites to be reached (or complete washout from prior spironolactone). The broad study design will be designed around evaluation of change in urine sodium to potassium ratio, sodium output following a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo/placebo | Placebo comparator | Drug: PlaceboThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. |
| Placebo/Sprironolactone | Active comparator | Drug: Placebo, Drug: Spironolactone 25mgThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. |
| placebo/aldosterone | Active comparator | Drug: Placebo, Drug: AldosteroneThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. |
| aldosterone/spironolactone | Active comparator | Drug: Spironolactone 25mg, Drug: AldosteroneThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Chronic stable heart failure at optimal volume status. Inclusion will require participants to be NYHA class I or II.
- eGFR > 30 ml/min/1.73m2
- Serum potassium ≤5.0 meq/L and ≥3.5 meq/L
- Stable heart failure medications without need or expectation for changes during the 8-week study period
- Free from heart failure decompensation for the preceding 60 day
Key exclusion criteria (15 listed)
- Uncontrolled hypertension (SBP > 160 mmHg)
- Severe bladder dysfunction
- Current MRA dose > 50mg spironolactone or equivalent or non MRA potassium sparing diuretic such as amiloride
- Contraindication to initiation or withdrawal of spironolactone per study procedures
- History of severe hyperkalemia (K>6.0 meq/l)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. | Drug | Placebo/Sprironolactone, Placebo/placebo, placebo/aldosterone |
| Spironolactone 25mgThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. | Drug | Placebo/Sprironolactone, aldosterone/spironolactone |
| AldosteroneThis study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59. | Drug | aldosterone/spironolactone, placebo/aldosterone |
Primary outcome
change in urine sodium to potassium ratio
Time frame: 59 days
Change in sodium to potassium ratio between aldosterone vs vehicle infusion during the spironolactone vs. placebo arms.
2 secondary outcomes
Urine Sodium output following saline load
Time frame: 59 days
Natriuretic effect of adjuvant to loop diuretic therapy
Time frame: 59 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Testani, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone 25mg and Aldosterone in people with Heart Failure, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in urine sodium to potassium ratio (time frame: 59 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.