Sodium-Glucose Cotransporter-2 Inhibitor for Patients With Acute Cardiorenal Syndrome

NCT07273838 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20000389891K23DK142042-01A1
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Heart Failure; Acute Kidney Injury

Keywords

Acute cardiorenal syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  Calculated at 30 days post-randomization

Secondary Outcomes (30)

• Change in slope of serum creatinine over 14 days from enrollment

  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

  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

  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

  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

  Measured at the time of enrollment (day 0) and on days 1-4, and day 14 +/- 4 days

Study Arms (2)

SGLT2i

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Subjects receive once daily administration of a placebo comparator for 14 days (or until discharge).

Drug: Placebo

Interventions

Dapagliflozin 10mg Tab DRUG

Administration of 10mg oral dapagliflozin once daily for 14 days (or until discharge).

SGLT2i

Placebo DRUG

Administration of placebo comparator once daily for 14 days (or until discharge).

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged ≥ 18 and ≤ 85 years-old
• Diagnosed with heart failure of either preserved or reduced left ventricular function
• Have signs of heart failure exacerbation
• Ability to take an oral medication
• Willing to adhere to the SGLT2i vs placebo regimen

You may not qualify if:

• AKI can be primarily explained by another etiology
• Current use of SGLT2 inhibitor or exposure in the past 72 hours
• Pregnancy or lactation (pregnancy test prior to enrollment in women of child-bearing age)
• Known allergic reactions to components of an SGLT2 inhibitor
• Treatment with another investigational drug for heart failure different from or in addition to usual care within the 72 hours preceding AKI
• Any individual who meets any of the following criteria will be excluded from participation in this study:
• Documented history of ileal conduit (neobladder)
• No means of collecting urine such as patients with documented incontinence without indwelling or external urinary catheter
• Advanced kidney disease at baseline defined as baseline eGFR \< 25 ml/min/1.73m2
• Unexplained hypoglycemia in the past 30 days from enrollment
• History of Fournier's gangrene (pelvic necrotizing fasciitis)
• History of recurrent urinary tract infection (UTI): defined as documented UTI at least 2x in the preceding 6 months or 3 x in the preceding 12 months
• End-stage kidney disease with dialysis requirement
• Oliguria: defined as less than 30 ml urine output per hour for more than two consecutive hours or less than 500 ml over the preceding 24 hours
• Severe acute kidney injury with indications for dialysis

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Yale New Haven Hospital-St. Raphael Campus

New Haven, Connecticut, 06510, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure; Acute Kidney Injury

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Abinet Aklilu, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abinet Aklilu, MD

CONTACT

203-931-5064; abinet.aklilu@yale.edu

Francis Wilson

CONTACT

francis.p.wilson@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: December 10, 2025
• Study Start: March 5, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): October 31, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon publication; indefinitely.

Locations

US (2)