This study will enroll adults aged 18 to 80 years diagnosed with sepsis due to a suspected or confirmed bacterial infection, within 7 days of being admitted to the hospital, and who have also developed acute kidney injury within 72 hours of the onset of sepsis. Eligible participants will be randomly assigned to receive either AZD4144 or a placebo intravenously once daily for the number of days specified in the CSP. During this Treatment Period, participants will undergo daily safety monitoring, as well as blood and urine sample collection and other assessments. After the Treatment Period, participants will continue to be monitored for safety and other assessments during each additional day they remain hospitalized (if applicable) as well as during up to 2 follow up visits after discharge. The main goal is to compare specific kidney function measurements between those participants receiving AZD4144 and those receiving the placebo.
This is a Phase IIa, randomised, double-blind, placebo-controlled, multicenter study that will be conducted in adult participants (aged 18-80) with sepsis-associated acute kidney injury (SA-AKI). Eligible participants must have sepsis secondary to suspected or confirmed bacterial infection requiring vasopressor or inotrope therapy, and AKI (KDIGO Stage ≥ 1) within a defined time frame of sepsis onset. Participants will be randomised in a 1:1 ratio to receive either intravenous AZD4144 or matching placebo once daily for a fixed treatment period. The study will be comprised of: * A screening period * A treatment period, during which participants receive intravenous AZD4144 or placebo daily according to the protocol dosing days. * A follow-up period that will include daily assessments while still hospitalized and up to two additional outpatient visits at scheduled times after discharge.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
124
Intravenous solution of AZD4144 will be administered to randomised participants according to the treatment arm to which they have been assigned.
Intravenous solution of Placebo will be administered to randomised participants according to the treatment arm to which they have been assigned.
Research Site
Tucson, Arizona, United States
Research Site
Newport Beach, California, United States
Research Site
Baltimore, Maryland, United States
Research Site
Boston, Massachusetts, United States
Research Site
Detroit, Michigan, United States
Research Site
Area Under the Curve (AUC) of 24-hour Creatinine Clearance (CrCl).
The total area under the curve for 24-hour creatinine clearance measured throughout the treatment period.
Time frame: During the treatment period.
Days alive and free of KRT.
The total number of calendar days in which a patient is both alive and not receiving Kidney Replacement Therapy (KRT), such as dialysis.
Time frame: Through study completion, an average of 30 days.
Days alive and free of modified KDIGO AKI Stage 2 or 3.
The total number of calendar days in which a patient is alive and does not meet criteria for modified KDIGO Acute Kidney Injury (AKI) Stage 2 or 3. The modified KDIGO is a scale measuring AKI severity, ranging from 1 to 3 (most severe).
Time frame: Through study completion, an average of 30 days
AUC: Serum Creatinine
The area under the curve for serum creatinine to evaluate changes in renal function.
Time frame: During the treatment period.
AUC: Serum Cystatin C
The area under the curve for serum cystatin C to evaluate changes in renal function.
Time frame: During the treatment period
AUC: mGFR
The area under the curve for mGFR to evaluate changes in renal function.
Time frame: During the treatment period.
Cmax/Cbaseline: Serum creatinine
The ratio of peak serum creatinine to baseline.
Time frame: During the treatment period.
Cmax/Cbaseline: Serum cystatin C
The ratio of peak serum Cystatin C to baseline.
Time frame: During the treatment period.
AUC: Plasma IL-18
The area under the curve for plasma interleukin-18 measured as a marker of inflammation.
Time frame: During the treatment period.
AUC: Urine IL-18
The area under the curve for urine interleukin-18 measured as a marker of inflammation.
Time frame: During the treatment period.
AUC: Plasma IL-6
The area under the curve for plasma interleukin-6 measured as a marker of inflammation.
Time frame: During the treatment period.
AUC: Urine IL-6
The area under the curve for urine interleukin-6 measured as a marker of inflammation.
Time frame: During the treatment period.
Plasma concentrations of AZD4144
Measurement of AZD4144 plasma levels to evaluate pharmacokinetics in participants with SA-AKI.
Time frame: Through study completion, an average of 30 days
Occurrence of MAKE30
MAKE30 is defined as the occurrence of any of the following: * Decrease from pre-AKI reference eGFR ≥ 25% at Day 30, * Initiation of KRT at any time before Day 30, * Death from any cause up to Day 30.
Time frame: Through study completion, an average of 30 days
Days alive and free of mechanical ventilation
The total number of calendar days of which a patient is alive and not receiving mechanical ventilation.
Time frame: Through study completion, an average of 30 days.
Days alive and outside of the ICU
The total number of calendar days of which a patient is alive and not admitted to the intensive care unit (ICU).
Time frame: Through study completion, an average of 30 days.
Rehospitalisation
Occurrence of hospital readmission after initial discharge.
Time frame: Through study completion, an average of 30 days.
Days alive and free of hospitalisation
The total number of calendar days of which a patient is alive and not hospitalized.
Time frame: Through study completion, an average of 30 days.
Days alive and free of vasopressor and/or inotrope
The total number of calendar days of which a patient is alive and not requiring vasopressor or inotrope support.
Time frame: Through study completion, an average of 30 days.
AUC mSOFA score
The area under the curve for the modified Sequential Organ Failure Assessment (mSOFA) score to assess organ dysfunction. The modified mSOFA score is a scale to assess organ dysfunction, ranging from 0 (best outcome) to 4 (worst outcome).
Time frame: During the treatment period.
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