A Phase 2 interventional study of Dapagliflozin 10mg Tab and Placebo in Heart Failure and Acute Kidney Injury, sponsored by Yale University. Recruiting at 2 sites in United States. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-13.
Sponsored by Yale University · Phase 2, Interventional, and Treatment
The overall objective of this study is to determine whether the addition of SGLT2 inhibitors to usual care in hospitalized patients with heart failure associated acute kidney injury is safe and efficacious. Investigators will assess if SGLT2 inhibition improves a composite cardio-renal outcome (mortality, dialysis, AKI progression, decongestion metrics, heart failure symptoms). Secondary objectives of this study are to compare individual components of the composite outcome as well as changes in biomarkers of kidney injury, inflammation, repair and oxidative stress between those exposed to the SGLT2 inhibitor vs placebo.
Individuals with heart failure are prone to acute kidney injury (AKI) as well as fluctuations in creatinine that meet AKI criteria. AKI diagnosis often complicates heart failure management and leads to interruptions of medications with long term benefit. AKI is also associated with long-term complications such as chronic kidney function and cardiovascular mortality. There is no efficient universal treatment for this type of AKI. In acute heart failure (AHF), although loop diuretics are the mainstay of treatment, diuretic resistance complicates the management. A drug that improves diuretic efficiency may lead to faster decongestion and improvement in kidney function.
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are drugs consistently shown to reduce hospitalizations in heart failure as well as progression of chronic kidney disease. They have also shown to promote kidney tubular health in pre-clinical models of kidney injury. They have been included in the armamentarium of heart failure care as goal directed medical therapy (GDMT) but concerns of efficacy and safety in patients with kidney dysfunction continue to limit their uptake and maintenance.
This study aims to promote increased use of SGLT2 inhibitors by demonstrating their safety and possible benefit in patients who develop kidney injury in the setting of heart failure to avoid interruptions in GDMT use.
To this end, 130 hospitalized adults with acute cardiorenal syndrome will be enrolled into a randomized controlled trial. Subjects will be randomized to receive either dapagliflozin or placebo for 14 days or until discharge (whichever comes first). Blood and urine samples will be collected for biomarker analysis, symptom and adverse event surveys will be administered, and various clinical parameters will be recorded on up to 6 study visits during hospitalization.
The primary outcome is a composite of short- and intermediate-term cardiorenal outcomes including: heart failure specific outcomes (objective measures of decongestion (i.e., effective diuresis), and a patient-reported outcome incorporating two dimensions of health state and a visual analogue scale (VAS)), kidney-specific outcomes (dialysis receipt, AKI progression to a higher stage, and change in serum creatinine), length of stay, and mortality. Secondary outcomes include trends in biomarkers of kidney injury, inflammation, oxidative stress, and repair, as well as individual components of the primary outcome as well as re-hospitalization rates.
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's planned enrollment of 130 is above the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Subjects receive once daily 10 mg of oral dapagliflozin (Farxiga) for 14 days (or until discharge). Empaglifolozin may be used in case of dapagliflozin shortage.
Drug: Dapagliflozin 10mg Tab
Subjects receive once daily administration of a placebo comparator for 14 days (or until discharge).
Drug: Placebo
Administration of 10mg oral dapagliflozin once daily for 14 days (or until discharge).
Administration of placebo comparator once daily for 14 days (or until discharge).
Cardio-renal clinical improvement calculated as a Win Ratio
This outcome is assessed using a win ratio (total wins in the intervention group divided by total wins in the control group). Pairwise comparisons of predetermined components are made between each participant in the intervention and control group hierarchically in order of clinical importance, with a "win" assigned to the participant with the more favorable result at the first level of difference. The win ratio is the number of "winning" pairs for the treatment group divided by the number of "losing" pairs, with a win ratio greater than 1 indicating a benefit for the treatment.
Time frame: Calculated at 30 days post-randomization
Change in slope of serum creatinine over 14 days from enrollment
Measure of kidney function; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of serum cystatin-C over 14 days from enrollment
Measure of kidney function; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of serum serum NT-proBNP over 14 days from enrollment
Measure of kidney function; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood kidney injury molecule-1 (KIM-1) over 14 days from enrollment
Biomarker of renal tubular injury; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine kidney injury molecule-1 (KIM-1) over 14 days from enrollment
Biomarker of renal tubular injury; assessed as a change in urine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood neutrophil gelatinase-associated lipocalin (NGAL) over 14 days from enrollment
Biomarker of renal tubular injury; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine neutrophil gelatinase-associated lipocalin (NGAL) over 14 days from enrollment
Biomarker of renal tubular injury; assessed as a change in urine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood interleukin-6 (IL-6) over 14 days from enrollment
Biomarker of inflammation; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine interleukin-6 (IL-6) over 14 days from enrollment
Biomarker of inflammation; assessed as a change in urine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood interluekin-18 (IL-18) over 14 days from enrollment
Biomarker of inflammation; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine interluekin-18 (IL-18) over 14 days from enrollment
Biomarker of inflammation; assessed as a change inurine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood MPO over 14 days from enrollment
Biomarker of oxidative stress; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine MPO over 14 days from enrollment
Biomarker of oxidative stress; assessed as a change in urine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood uromodulin (UMOD) over 14 days from enrollment
Biomarker of repair; assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine uromodulin (UMOD) over 14 days from enrollment
Biomarker of repair; assessed as a change in urine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of blood chitinase-3-like protein 1 (YKL-40) over 14 days from enrollment
Biomarker of repair. Assessed as a change in blood concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine chitinase-3-like protein 1 (YKL-40) over 14 days from enrollment
Biomarker of repair. Assessed as a change in urine concentration.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days
Change in slope of urine volume over 5 days from enrollment
Measure of decongestion; measured daily (i.e. every 24 hours) according to floor protocol.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4 post-enrollment
Change in slope of weight over 14 days from enrollment
Measure of decongestion; assessed upon physical exam.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4 and 14 post-enrollment
Change in slope of breathlessness score over 14 days from enrollment
Measure of decongestion using a survey, scored on a Likert scale from 1-5 (5 indicates more severe breathlessness).
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 post-enrollment
Change in slope of edema grade over 14 days from enrollment
Measure of decongestion; a score from 0 to 4+ is given on physical examination, with a higher score indicating higher edema.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 post-enrollment
Change in slope of patient-reported edema over 14 days from enrollment
Measure of decongestion using a survey, scored on a Likert scale from 1-5 (5 indicates more severe edema).
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 post-enrollment
Change in slope of patient-reported VAS dyspnea score over 14 days from enrollment
A patient reported outcome measured on a visual analog scale of 1-100mm, with 100 indicating worse breathlessness.
Time frame: Measured at the time of enrollment (day 0) and on days 1-4, and day 14 post-enrollment
Cumulative Lasix equivalent diuretic dose over 5 days
Measure of decongestion
Time frame: Up to 5 days from enrollment
Proportion with kidney injury progression
Proportion with dialysis receipt or AKI progression to a higher stage up to 14 days from enrollment
Time frame: Up to 14 days post-enrollment
Percent survival at 30 days post-enrollment
Percent of subject's surviving to 30 days post-enrollment
Time frame: Up to 30 days post-enrollment
Percent of subjects re-hospitalized with heart failure and AKI at 30 days post-enrollment
Percent of rehospitalization up to 30 days post-enrollment
Time frame: Up to 30 days post-enrollment
Proportion with prescription of SGLT2i
Proportion with prescription of SGLT2i by subject's own provider
Time frame: Up to 30 days post-enrollment
Incidence of adverse events during exposure
Number of adverse events experienced by subjects, including sodium or potassium derangements, metabolic acidosis, urinary tract infections, fungal genitourinary infection, hypotension, allergic reactions, and hypoglycemia
Time frame: Up to 14 days post-enrollment or until hospital discharge
Change in heart failure symptoms (mobility and self care)
Change in score using a full and modified version of the EQ-5D-5L-VAS. The full questionnaire contains 5 dimensions of state of health and the VAS (visual analog scale) addressing perceived overall health and will be conducted on day 0 and 14. The modified version contains two dimensions of health (self care and mobility) and the VAS scale, and will be conducted on days 1, 2, 3, and 4. The EQ-5D-5L dimensions are scored on a Likert Scale from 1-5, with 5 indicating worsening health. The VAS is scored on a scale of 1 to 100, with 100 indicating better perceived overall health.
Time frame: Measured on Days 0, 1, 2, 3, 4, and 14 post-enrollment
Plan to share: Yes — De-identified data for the primary and secondary outcomes will be made available.
Supporting information: Study protocol, Sap, Icf
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