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

NCT ID: NCT07273838

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2029-05-31

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.

Detailed Description

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.

Conditions

Heart Failure; Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SGLT2i

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.

Group Type: EXPERIMENTAL

Dapagliflozin 10mg Tab

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Dapagliflozin 10mg Tab

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Current dialysis receipt for acute kidney injury
• Comfort measures only
• Solid organ transplant on immunosuppression

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abinet Aklilu, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale New Haven Hospital-St. Raphael Campus

New Haven, Connecticut, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Countries

United States

Central Contacts

Abinet Aklilu, MD

Role: CONTACT

abinet.aklilu@yale.edu

203-931-5064

Francis Wilson

Role: CONTACT

francis.p.wilson@yale.edu

Facility Contacts

Abinet Aklilu, MD

Role: primary

Abinet Aklilu, MD

Role: primary

Other Identifiers

1K23DK142042-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000038989

Identifier Type: -

Identifier Source: org_study_id