Heart FailurePhase 2NCT04438213
Ertugliflozin in Chronic Heart Failure
A Phase 2 study testing Ertugliflozin and Metolazone in people with Heart Failure, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to determine the effects on heart failure signs and symptoms of the use of either ertugliflozin, metolazone or placebo, in conjunction with intravenous loop diuretic use in acute settings and chronic oral loop diuretic therapy. There are two general purposes for this study. 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?
- Ertugliflozin and Metolazone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2021to 30 Dec 2025
- Phase
- Phase 2
- 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 chronic heart failure (either systolic or diastolic)
- Chronic daily oral loop diuretic dose use
- eGFR ≥20 mL/min/1.73 m2
- English speaking participants only
- Signed informed consent
Who cannot join
- Current use or plan to initiate renal replacement therapy or ultrafiltration
- Significant bladder dysfunction or urinary incontinence
- Inability to comply with the serial urine collection procedures
- Current use of a thiazide or thiazide like diuretics or use within 5 half-lives of the drug, including metolazone
- Current use of a SGLT-2 inhibitor, or in the treating provider's judgement, contraindication to be withdrawn from current use of an SGLT-2 inhibitor
- Prior heart transplant, critical stenotic valvular disease or complex congenital heart
Show all 14Show 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 3 months
- History of or current urosepsis or frequent urinary tract infections
- Anemia with hemoglobin <8g/dL (due to required phlebotomy for the study)
- 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)
- Inability to give written informed consent or follow study protocol
- Severe peripheral artery disease, previous amputation, or threatened amputation
- Life expectancy < 3 months
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale School of Medicine
New Haven, Connecticut, 06510
Jeffrey Testani, MD
About this study
Official title: Ertugliflozin in Chronic Heart Failure: Cardio-renal and Diuretic Effects
The purpose of this study is to determine the effects on heart failure signs and symptoms of the use of either ertugliflozin, metolazone or placebo, in conjunction with intravenous loop diuretic use in acute settings and chronic oral loop diuretic therapy.
There are two general purposes for this study. The proposed study is both larger and more rigorous than essentially all PK/PD studies that form the basis of current practice with loop diuretics as well as all studies looking at add-on thiazide therapy (current guideline-recommended adjuvant). The second is to generate a mechanistic understanding of the pleotropic cardio-renal factors with chronic therapy that differentiate ertugliflozin from traditional diuretics particularly in how they maintain reduced blood volume without the complication of over-diuresis and volume depletion.
Read the detailed description
This is a randomized placebo controlled mechanistic study to understand the utility of ertugliflozin in heart failure patients with or without diabetes, compared to both placebo and the active control metolazone. The broad study design will be designed around evaluation of change in gold standard determined body fluid spaces (blood volume, extracellular fluid, total body water), administering a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses. The general study design will randomize to ertugliflozin vs. placebo for a total therapy of 6 weeks.
- Conditions
- Heart Failure
- Being tested
- Ertugliflozin, Metolazone, Placebo
- Keywords
- Ertugliflozin, Metolazone
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErtugliflozinDrug
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
MetolazoneDrug
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
PlaceboDrug
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo
| Study group | Role | What they receive |
|---|---|---|
| Ertugliflozin | Experimental | Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo Receives: Drug: Ertugliflozin |
| Metolazone | Experimental | Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo Receives: Drug: Metolazone |
| Placebo | Placebo comparator | Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to day 7 of plasma volume by add-on to loop diuretic therapy
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in plasma volume from baseline to day 7
Measured: 7 days
Change from baseline to 6 weeks of plasma volume by add-on to loop diuretic therapy
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in plasma volume from baseline to 6 weeks
Measured: 6 weeks
Natriuretic effect of adjuvant to loop diuretic therapy
The natriuretic effect of each arm with loop diuretic therapy will be measured by the urine sodium output and FeNa.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start10 Mar 2021
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2025 (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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Jeffrey Testani, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04438213
- Sponsor's protocol ID
- 2000027951
- Other IDs
- MISP59625
- Status last verified
- Oct 2025
- First submitted
- 3 Jun 2020
- Last updated
- 8 Oct 2025
- 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 8 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ertugliflozin in Chronic Heart Failure: Cardio-renal and Diuretic Effects
- ClinicalTrials.gov ID
- NCT04438213
- Acronym / sponsor ID
- 2000027951
- Conditions
- Heart Failure
- Keywords
- Ertugliflozin, Metolazone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 10 Mar 2021 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 18 Jun 2020 (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 study is to determine the effects on heart failure signs and symptoms of the use of either ertugliflozin, metolazone or placebo, in conjunction with intravenous loop diuretic use in acute settings and chronic oral loop diuretic therapy.
There are two general purposes for this study. The proposed study is both larger and more rigorous than essentially all PK/PD studies that form the basis of current practice with loop diuretics as well as all studies looking at add-on thiazide therapy (current guideline-recommended adjuvant). The second is to generate a mechanistic understanding of the pleotropic cardio-renal factors with chronic therapy that differentiate ertugliflozin from traditional diuretics particularly in how they maintain reduced blood volume without the complication of over-diuresis and volume depletion.
Detailed description
This is a randomized placebo controlled mechanistic study to understand the utility of ertugliflozin in heart failure patients with or without diabetes, compared to both placebo and the active control metolazone. The broad study design will be designed around evaluation of change in gold standard determined body fluid spaces (blood volume, extracellular fluid, total body water), administering a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses. The general study design will randomize to ertugliflozin vs. placebo for a total therapy of 6 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ertugliflozin | Experimental | Drug: ErtugliflozinParticipants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo |
| Metolazone | Experimental | Drug: MetolazoneParticipants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- A clinical diagnosis of chronic heart failure (either systolic or diastolic)
- Chronic daily oral loop diuretic dose use
- eGFR ≥20 mL/min/1.73 m2
- English speaking participants only
- Signed informed consent
Key exclusion criteria (14 listed)
- Current use or plan to initiate renal replacement therapy or ultrafiltration
- Significant bladder dysfunction or urinary incontinence
- Inability to comply with the serial urine collection procedures
- Current use of a thiazide or thiazide like diuretics or use within 5 half-lives of the drug, including metolazone
- Current use of a SGLT-2 inhibitor, or in the treating provider's judgement, contraindication to be withdrawn from current use of an SGLT-2 inhibitor
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 |
|---|---|---|
| ErtugliflozinParticipants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo | Drug | Ertugliflozin |
| MetolazoneParticipants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo | Drug | Metolazone |
| PlaceboParticipants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo | Drug | Placebo |
Primary outcome
Change from baseline to day 7 of plasma volume by add-on to loop diuretic therapy
Time frame: 7 days
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in plasma volume from baseline to day 7
Change from baseline to 6 weeks of plasma volume by add-on to loop diuretic therapy
Time frame: 6 weeks
The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in plasma volume from baseline to 6 weeks
Natriuretic effect of adjuvant to loop diuretic therapy
Time frame: 1 day
The natriuretic effect of each arm with loop diuretic therapy will be measured by the urine sodium output and FeNa.
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 8 Oct 2025.
- 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.
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 2 study testing Ertugliflozin and Metolazone 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 5 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 8 Oct 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Veena Rao, PHD ((203) 737-3571, veena.s.rao@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline to day 7 of plasma volume by add-on to loop diuretic therapy (time frame: 7 days). 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 8 Oct 2025.