Clinical trial NCT06111768: Sodium-Glucose Cotransporter-2 Inhibitor for Acute Cardiorenal Syndrome: A Feasibility Study
Official title: Sodium-Glucose Cotransporter-2 Inhibitor for Acute Cardiorenal Syndrome: A Feasibility Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cardiorenal Syndrome
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2023-11-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The long-term objective of this study is to test whether the addition of SGLT2 inhibitors to usual care during acute heart failure management in patients who develop kidney injury shortens the time to achieving symptomatic improvement and kidney function recovery. The study aims to assess feasibility and acceptability of such a randomized clinical trial.

Detailed description: Acute heart failure is associated with a significant risk of acute kidney injury which is present in up to a third of patients at the time of hospitalization. As adequate kidney function is necessary for self-decongestion, kidney injury makes the treatment of acute heart failure particularly challenging. SGLT2i are drugs consistently shown to reduce hospitalizations in heart failure as well as progression of kidney disease but are frequently discontinued during acute kidney injury. Although they have been included in the armamentarium of heart failure care as guideline directed medical therapy, a concern about the efficacy and safety in patients with kidney dysfunction remains a limitation to their widespread uptake particularly during heart failure exacerbation.

This study aims to enroll adults hospitalized with acute congestive cardiorenal syndrome and develop acute kidney injury in a randomized clinical trial of SGLT2i versus usual care to compare markers of decongestion and biomarkers of kidney injury and health to inform a larger randomized clinical trial. The overall aim is to assess if SGLT2i improve diuretic efficiency in patients with heart failure associated kidney injury. The long-term goal of this study is to promote increased use of SGLT2i by demonstrating their safety and possible benefit in patients who develop heart failure associated kidney injury to avoid interruptions in this setting.

The primary objective of this is study is to test the feasibility and acceptability of randomizing adults hospitalized with acute heart failure complicated by acute kidney injury to SGLT2i or usual care.

The secondary objectives of this study are:

1. To compare changes in biomarkers of kidney injury, repair and tubular function in order to test whether the SGLT2 inhibitor (dapagliflozin) improves response to standard treatment
2. To compare markers of decongestion (weight, urine volume, symptom score, diuretic de-escalation) to test whether the addition of SGLT2i to standard of care improves heart failure symptoms faster.
3. To compare possible adverse events such as: sodium or potassium derangements, metabolic acidosis, urinary tract infections (UTI) or genital mycotic infections in those exposed to the SGLT2i dapagliflozin vs usual care.
4. To compare hospital length of stay, mortality, progression to a higher stage of AKI, and persistent AKI at discharge

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged ≥ 18 and ≤ 85 years-old
4. Diagnosed with heart failure of either preserved or reduced left ventricular function
5. NT-proBNP \> 300 pg/mL
6. Ability to take an oral medication
7. Willing to adhere to the SGLT2i + usual care regimen

Exclusion Criteria:

1. Current use of SGLT2 inhibitor or use in the past 72 hours
2. Pregnancy or lactation (a pregnancy test will be performed prior to enrollment in women of child-bearing age)
3. Known allergic reactions to components of an SGLT2 inhibitor
4. Treatment with another investigational drug for heart failure different from or in addition to usual care within the 72 hours preceding AKI
5. 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 past 6 months or 3 x in the past 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

Primary outcomes:
measure: Percentage of eligible versus consented patients
timeFrame: From study initiation to study close (about 2 years)
measure: Percentage of enrolled patients with completed sample collections
timeFrame: From study initiation to study close (about 2 years)
measure: Enrollment rate
timeFrame: From study initiation to study close (about 2 years)
Secondary outcomes:
measure: Slope of creatinine
timeFrame: 5 days following randomization
measure: Slope of cystatin-C
timeFrame: 5 days following randomization
measure: Slope of NT-proBNP
timeFrame: 5 days following randomization
measure: Slope of kidney tubular injury and repair biomarkers
timeFrame: 5 days following randomization
measure: Slope of urine volume
timeFrame: 72 hours from randomization
measure: Weight
timeFrame: 72 hours from randomization
measure: Breathlessness score
timeFrame: 72 hours from randomization
measure: Loop diuretic dose de-escalation
timeFrame: From randomization up to 72 hours from randomization
measure: Mortality
timeFrame: Assessed from randomization to time of death up to 14 days post-randomization or discharge
measure: Dialysis
timeFrame: Assessed from point of randomization to the date of first documented dialysis order during index hospitalization, up to 14 days post-randomization or discharge
measure: Rate of rehospitalization with heart failure
timeFrame: 90 days post-index discharge
measure: Time-to-prescription of an SGLT2i
timeFrame: 90 days post-randomization
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Abinet Aklilu
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Perry Wilson
role: PRINCIPAL_INVESTIGATOR
References: