Heart FailurePhase 1EMPANCT03027960
Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects
A Phase 1 study testing Empagliflozin in people with Heart Failure and Type II; Diabetes, run by Yale University at 1 site in United States.
Trial summary
The investigators propose a small pilot proof of concept study to not only prove the existence of, but also probe the mechanisms underlying cardio-renal effects of empagliflozin in patients with heart failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Type II; Diabetes
- What is being tested?
- Empagliflozin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2017to 1 Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Stable HF as defined by:
- No hospitalization for >60 days
- Stable HF medications for >=2 weeks, and stable diuretics for 4 weeks
- Opinion of HF cardiologist that the patient is at their optimal volume status
- Chronic daily oral loop diuretic dose >=20mg furosemide equivalents
- Diagnosis of type II diabetes
Show all 9Show fewer
- Patient monitors blood glucose regularly at home
- eGFR >=45 mL/min/1.73 m2
- >=18 years old
Who cannot join
- Active titration of chronic HF medications expected during the study period
- Use of a non-loop diuretic, aside from an aldosterone antagonist (<=25mg spironolactone or <=50mg eplerenone)
- Critical stenotic valvular disease, complex congenital heart disease, or prior heart transplant
- History of diabetic ketoacidosis, "brittle" diabetes, and/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 bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections
- Anemia (defined as hemoglobin <8g/dL)
Show all 12Show fewer
- Pregnancy or breastfeeding
- History of serious hypersensitivity
- Participation in another trial with an investigational drug within the 30 days prior to informed consent
- Use of another SGLT-2 inhibitor
- Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research RN (ex: clinically-significant psychiatric, addictive, or neurological disease)
- Inability to give written informed consent or follow study protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06511
About this study
The investigators propose a small pilot proof of concept study to not only prove the existence of, but also probe the mechanisms underlying cardio-renal effects of empagliflozin in patients with heart failure. The investigators propose a 50 patient randomized, double-blind, placebo-controlled crossover study with patients with stable HF, type II diabetes and an eGFR >45ml/min/1.73 m2 who are chronically receiving loop diuretics.
Read the detailed description
Study Objectives
- Study the acute/short term effect and cardio-renal mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition in patients with heart failure.
- Determine the effect of chronic combined SLLGT2 and loop diuretic exposure in patients with heart failure.
Primary Outcomes
- Aim 1 (Acute): Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo.
- Aim 2 (Chronic): Determine the effect of 14 days of SGLT2 inhibition on blood volume.
- Conditions
- Heart Failure, Type II; Diabetes
- Being tested
- Empagliflozin, Placebo Oral Capsule
- Keywords
- cardio-renal
- Medical subject headings
- Heart Failure, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
10mg empagliflozin for a 2-week period
Placebo Oral CapsuleDrug
10 mg placebo for a 2-week period
| Study group | Role | What they receive |
|---|---|---|
| Placebo, then empagliflozin | Experimental | Patients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. Receives: Drug: Empagliflozin; Drug: Placebo Oral Capsule |
| Empagliflozin, then Placebo | Experimental | Patients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. Receives: Drug: Empagliflozin; Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
urine sodium concentrations via ion selective electrodes
Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo.
Measuring the natriuretic effect of a loop diuretic (placebo v acute SGLT2 inhibition) via urine sodium output.
Measured: 36 days
Secondary outcomes (1)
blood volume
Determine the effect of 14 days of SGLT2 inhibition on blood volume.
Daxor Blood Volume Sample Collection
- Volumex Injection: The Volumex tracer (radiolabeled albumin) is injected as an intravenous bolus (IV-push). (As soon as the tracer injection begins, a stopwatch is started and never zeroed out. Running times are used for the entire procedure).
- Serial Blood Collection A series of 5 post-Volumex blood samples is collected, after tracer injection, allowing for complete mixing in the bloodstream.
- Sample Timing: Samples are ideally spaced ~6 minutes apart, and are collected approximately 12, 18, 24, 30 and 36 minutes after Volumex administration.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2017 (estimated)
- Study start27 Jun 2017
- Primary completion14 May 2019
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- 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
- NCT03027960
- Sponsor's protocol ID
- 2000020019
- Acronym
- EMPA
- Status last verified
- Jun 2020
- First submitted
- 17 Jan 2017
- Last updated
- 26 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rao VS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, Maulion C, Bellumkonda L, Chang J, Field MP, Wiederin DR, Butler J, Collins SP, Turner JM, Wilson FP, Inzucchi SE, Wilcox CS, Ellison DH, Testani JM. Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects. J Am Soc Nephrol. 2024 Feb 1;35(2):189-201. doi: 10.1681/ASN.0000000000000269. Epub 2023 Dec 11.
PubMed 38073038Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects. Circulation. 2020 Sep 15;142(11):1028-1039. doi: 10.1161/CIRCULATIONAHA.120.045691. Epub 2020 May 15.
PubMed 32410463
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects
- ClinicalTrials.gov ID
- NCT03027960
- Acronym / sponsor ID
- EMPA / 2000020019
- Conditions
- Heart Failure, Type II; Diabetes
- Keywords
- cardio-renal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 27 Jun 2017 (actual)
- Primary completion
- 14 May 2019 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 23 Jan 2017 (estimated)
- 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 investigators propose a small pilot proof of concept study to not only prove the existence of, but also probe the mechanisms underlying cardio-renal effects of empagliflozin in patients with heart failure. The investigators propose a 50 patient randomized, double-blind, placebo-controlled crossover study with patients with stable HF, type II diabetes and an eGFR >45ml/min/1.73 m2 who are chronically receiving loop diuretics.
Detailed description
Study Objectives
- Study the acute/short term effect and cardio-renal mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition in patients with heart failure.
- Determine the effect of chronic combined SLLGT2 and loop diuretic exposure in patients with heart failure.
Primary Outcomes
- Aim 1 (Acute): Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo.
- Aim 2 (Chronic): Determine the effect of 14 days of SGLT2 inhibition on blood volume.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo, then empagliflozin | Experimental | Drug: Empagliflozin, Drug: Placebo Oral CapsulePatients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. |
| Empagliflozin, then Placebo | Experimental | Drug: Empagliflozin, Drug: Placebo Oral CapsulePatients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Stable HF as defined by:
- No hospitalization for >60 days
- Stable HF medications for >=2 weeks, and stable diuretics for 4 weeks
- Opinion of HF cardiologist that the patient is at their optimal volume status
- Chronic daily oral loop diuretic dose >=20mg furosemide equivalents
Key exclusion criteria (12 listed)
- Active titration of chronic HF medications expected during the study period
- Use of a non-loop diuretic, aside from an aldosterone antagonist (<=25mg spironolactone or <=50mg eplerenone)
- Critical stenotic valvular disease, complex congenital heart disease, or prior heart transplant
- History of diabetic ketoacidosis, "brittle" diabetes, and/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 bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections
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 |
|---|---|---|
| Empagliflozin10mg empagliflozin for a 2-week period | Drug | Empagliflozin, then Placebo, Placebo, then empagliflozin |
| Placebo Oral Capsule10 mg placebo for a 2-week period | Drug | Empagliflozin, then Placebo, Placebo, then empagliflozin |
Primary outcome
urine sodium concentrations via ion selective electrodes
Time frame: 36 days
Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo. Measuring the natriuretic effect of a loop diuretic (placebo v acute SGLT2 inhibition) via urine sodium output.
1 secondary outcome
blood volume
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2020.
- Derived from this study: PubMed 38073038Rao VS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, Maulion C, Bellumkonda L, Chang J, Field MP, Wiederin DR, Butler J, Collins SP, Turner JM, Wilson FP, Inzucchi SE, Wilcox CS, Ellison DH, Testani JM. Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects. J Am Soc Nephrol. 2024 Feb 1;35(2):189-201. doi: 10.1681/ASN.0000000000000269. Epub 2023 Dec 11.
- Derived from this study: PubMed 32410463Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects. Circulation. 2020 Sep 15;142(11):1028-1039. doi: 10.1161/CIRCULATIONAHA.120.045691. Epub 2020 May 15.
- 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 1 study testing Empagliflozin in people with Heart Failure and Type II; Diabetes, 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 9 inclusion and 12 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: finished, as of the sponsor's last update on 26 Jun 2020. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
urine sodium concentrations via ion selective electrodes (time frame: 36 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03027960, which also lists 2 linked publications.
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 Jun 2020.