Heart FailurePhase 1EMPA HFNCT05553938
Effects of Acute and Chronic Empagliflozin Heart Failure
A Phase 1 study testing Empagliflozin 10 mg in people with Heart Failure, run by Yale University at 2 sites in United States.
Trial summary
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. 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?
- Empagliflozin 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Aug 2023to 14 Aug 2026
- Phase
- Phase 1
- 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
- A clinical diagnosis of worsening heart failure (worsening of congestive symptoms with current therapies) in the opinion of the investigator.
- A planned outpatient diuretic intervention (either up-titration of loop or addition of thiazide diuretic) for worsening heart failure per treating clinician. Diuretic intervention can occur via an unplanned in person visit (e.g., outpatient ambulatory clinic, emergency department, same day access visit) or via a telephone encounter (e.g., patient calling the clinic with reported weight gain and SOB that is prescribed uptitration of diuretic therapy).
- Estimated or reported weight gain of at least 5 lbs.
- Chronic daily oral loop diuretic dose ≥ 20mg furosemide equivalents for at least one month prior to enrollment
- Estimated GFR (eGFR) ≥ 20 mL/min/1.73 m2
- Age ≥ 18 years old
- Signed informed consent
- English speaking participants only
Who cannot join
- Need for heart failure hospitalization at the time of randomization
- Current use or plan to initiate renal replacement therapy
- Significant bladder dysfunction or urinary incontinence
- Inability to comply with the serial urine collection procedures
- Chronic use of natriuretic doses of thiazide diuretics (≥50mg hydrochlorothiazide or equivalent)
- Critical stenotic valvular disease, complex congenital heart disease or prior heart transplant
Show all 11Show fewer
- History of type 1 diabetes, diabetic ketoacidosis, "brittle" diabetes or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 6 months
- History of or current urosepsis or frequent urinary tract infections
- Anemia with hemoglobin <8g/dL (due to required phlebotomy for the study) or active bleeding
- Pregnancy or breastfeeding
- Appears unlikely or unable to participate in the required study procedures, as assessed by the study PI, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale New Haven Hospital
New Haven, Connecticut, 06520
Yale University
New Haven, Connecticut, 06520
About this study
Official title: Renal Mechanistic Effects of Acute and Chronic Empagliflozin in Heart Failure
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. Participants will be randomized to empagliflozin or placebo for 6 weeks, followed by a crossover of placebo patients to active therapy at 6 weeks-12 weeks.
Read the detailed description
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes.
The broad study design aims to evaluate change in gold standard determined body fluid spaces, sodium avidity, and cardio-renal biomarkers longitudinally in patients treated with placebo vs. empagliflozin over a 6 week period. Primary analysis of the randomized intervention will occur during the 6 week double blind period. Crossover of placebo patients to active therapy from 6-12 weeks will provide additional exploratory mechanistic data at low incremental cost and provide added benefit to enrollment of the study.
- Conditions
- Heart Failure
- Being tested
- Empagliflozin 10 mg, Placebo
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 mgDrug
Empagliflozin 10mg
PlaceboDrug
Empagliflozin matched placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Experimental | Empagliflozin 10 mg daily for weeks 1-6 Receives: Drug: Empagliflozin 10 mg |
| Placebo, Then Empagliflozin | Experimental | Participants first receive matching placebo daily for weeks 1-6, then will receive Empagliflozin 10 mg daily for weeks 7-12 Receives: Drug: Empagliflozin 10 mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy
The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the mmols of sodium excreted on day 1.
Measured: Day 1
Change in plasma volume from baseline to 7 days
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in plasma volume [ml] from Day 1 to Day 7, using I-131 albumin
Measured: Day 1 and Day 7
Change in total body water from baseline to 7 days
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in total body water [liters] from Day 1 to Day 7, using heavy water [D2O)
Measured: Day 1 and Day 7
Secondary outcomes (4)
Change in Chronic effects of empagliflozin vs placebo on plasma volume
Chronic effects of empagliflozin vs placebo on change in plasma volume [ml] will be measured on Day 1 and Day 42, using I-131 albumin
Measured: Day 1 and day 42
Change in Chronic effects of empagliflozin vs placebo on change in total body water
Chronic effects of empagliflozin vs placebo on change in total body water [liters] will be measured on Day 1 and Day 42, using heavy water [D2O]
Measured: Day 1 and day 42
Change in Chronic effects of empagliflozin on change in plasma volume during the open label extension.
Changes in plasma volume[ml] from Day 1 to Day 84 will be assessed during the open label extension, using I-131 albumin
Measured: Day 1 up to Day 84
Change in Chronic effects of empagliflozin on change in total body water during the open label extension.
Changes in total body water [liters] from Day 1 to Day 84 will be assessed during the open label extension, using heavy water [D2O]
Measured: Day 1 up to Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2022
- Study start4 Aug 2023
- Primary completion8 May 2026
- Study completion14 Aug 2026 (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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blind placebo controlled, with crossover for placebo patients to active drug at 6 weeks. (At 6 weeks, participants are unblinded, and participants who received placebo will receive study drug.)
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Testani, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05553938
- Sponsor's protocol ID
- 2000033412
- Acronym
- EMPA HF
- Status last verified
- Jun 2026
- First submitted
- 21 Sep 2022
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Mechanistic Effects of Acute and Chronic Empagliflozin in Heart Failure
- ClinicalTrials.gov ID
- NCT05553938
- Acronym / sponsor ID
- EMPA HF / 2000033412
- Conditions
- Heart Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 4 Aug 2023 (actual)
- Primary completion
- 8 May 2026 (actual)
- Study completion
- 14 Aug 2026 (estimated)
- First posted
- 26 Sep 2022 (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.
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. Participants will be randomized to empagliflozin or placebo for 6 weeks, followed by a crossover of placebo patients to active therapy at 6 weeks-12 weeks.
Detailed description
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes.
The broad study design aims to evaluate change in gold standard determined body fluid spaces, sodium avidity, and cardio-renal biomarkers longitudinally in patients treated with placebo vs. empagliflozin over a 6 week period. Primary analysis of the randomized intervention will occur during the 6 week double blind period. Crossover of placebo patients to active therapy from 6-12 weeks will provide additional exploratory mechanistic data at low incremental cost and provide added benefit to enrollment of the study.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Double blind placebo controlled, with crossover for placebo patients to active drug at 6 weeks. (At 6 weeks, participants are unblinded, and participants who received placebo will receive study drug.)
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Experimental | Drug: Empagliflozin 10 mgEmpagliflozin 10 mg daily for weeks 1-6 |
| Placebo, Then Empagliflozin | Experimental | Drug: Empagliflozin 10 mg, Drug: PlaceboParticipants first receive matching placebo daily for weeks 1-6, then will receive Empagliflozin 10 mg daily for weeks 7-12 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- A clinical diagnosis of worsening heart failure (worsening of congestive symptoms with current therapies) in the opinion of the investigator.
- A planned outpatient diuretic intervention (either up-titration of loop or addition of thiazide diuretic) for worsening heart failure per treating clinician. Diuretic intervention can occur via an unplanned in person visit (e.g., outpatient ambulatory clinic, emergency department, same day access visit) or via a telephone encounter (e.g., patient calling the clinic with reported weight gain and SOB that is prescribed uptitration of diuretic therapy).
- Estimated or reported weight gain of at least 5 lbs.
- Chronic daily oral loop diuretic dose ≥ 20mg furosemide equivalents for at least one month prior to enrollment
- Estimated GFR (eGFR) ≥ 20 mL/min/1.73 m2
Key exclusion criteria (11 listed)
- Need for heart failure hospitalization at the time of randomization
- Current use or plan to initiate renal replacement therapy
- Significant bladder dysfunction or urinary incontinence
- Inability to comply with the serial urine collection procedures
- Chronic use of natriuretic doses of thiazide diuretics (≥50mg hydrochlorothiazide or equivalent)
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 |
|---|---|---|
| Empagliflozin 10 mgEmpagliflozin 10mg | Drug | Empagliflozin, Placebo, Then Empagliflozin |
| PlaceboEmpagliflozin matched placebo tablet | Drug | Placebo, Then Empagliflozin |
Primary outcome
Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy
Time frame: Day 1
The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the mmols of sodium excreted on day 1.
Change in plasma volume from baseline to 7 days
Time frame: Day 1 and Day 7
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in plasma volume [ml] from Day 1 to Day 7, using I-131 albumin
Change in total body water from baseline to 7 days
Time frame: Day 1 and Day 7
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in total body water [liters] from Day 1 to Day 7, using heavy water [D2O)
4 secondary outcomes
Change in Chronic effects of empagliflozin vs placebo on plasma volume
Time frame: Day 1 and day 42
Change in Chronic effects of empagliflozin vs placebo on change in total body water
Time frame: Day 1 and day 42
Change in Chronic effects of empagliflozin on change in plasma volume during the open label extension.
Time frame: Day 1 up to Day 84
Change in Chronic effects of empagliflozin on change in total body water during the open label extension.
Time frame: Day 1 up to Day 84
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 2 Jul 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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Empagliflozin 10 mg in people with Heart Failure, run by Yale University at 2 sites 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 8 inclusion and 11 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 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy (time frame: Day 1). The study lists 3 primary outcomes in all. 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 2 Jul 2026.