A Study to Investigate the Efficacy, Safety, and Tolerability of AZD4144in Participants With Sepsis-associated Acute Kidney Injury.
- Conditions
- SepsisAcute Kidney Injury
- Interventions
- Drug: Placebo
- Registration Number
- NCT07215702
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 (AZD4144) AZD4144 AZD4144 solution for IV infusion Arm 2 (Placebo) Placebo Placebo concentrate for solution for infusion
- Primary Outcome Measures
Name Time Method Area Under the Curve (AUC) of 24-hour Creatinine Clearance (CrCl). During the treatment period. The total area under the curve for 24-hour creatinine clearance measured throughout the treatment period.
- Secondary Outcome Measures
Name Time Method Days alive and free of KRT. Through study completion, an average of 30 days. The total number of calendar days in which a patient is both alive and not receiving Kidney Replacement Therapy (KRT), such as dialysis.
Days alive and free of modified KDIGO AKI Stage 2 or 3. Through study completion, an average of 30 days 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).
AUC: Serum Creatinine During the treatment period. The area under the curve for serum creatinine to evaluate changes in renal function.
AUC: Serum Cystatin C During the treatment period The area under the curve for serum cystatin C to evaluate changes in renal function.
Cmax/Cbaseline: Serum cystatin C During the treatment period. The ratio of peak serum Cystatin C to baseline.
AUC: mGFR During the treatment period. The area under the curve for mGFR to evaluate changes in renal function.
Cmax/Cbaseline: Serum creatinine During the treatment period. The ratio of peak serum creatinine to baseline.
AUC: Plasma IL-18 During the treatment period. The area under the curve for plasma interleukin-18 measured as a marker of inflammation.
AUC: Urine IL-18 During the treatment period. The area under the curve for urine interleukin-18 measured as a marker of inflammation.
AUC: Plasma IL-6 During the treatment period. The area under the curve for plasma interleukin-6 measured as a marker of inflammation.
AUC: Urine IL-6 During the treatment period. The area under the curve for urine interleukin-6 measured as a marker of inflammation.
Plasma concentrations of AZD4144 Through study completion, an average of 30 days Measurement of AZD4144 plasma levels to evaluate pharmacokinetics in participants with SA-AKI.
Occurrence of MAKE30 Through study completion, an average of 30 days 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.Days alive and free of mechanical ventilation Through study completion, an average of 30 days. The total number of calendar days of which a patient is alive and not receiving mechanical ventilation.
Days alive and outside of the ICU Through study completion, an average of 30 days. The total number of calendar days of which a patient is alive and not admitted to the intensive care unit (ICU).
Rehospitalisation Through study completion, an average of 30 days. Occurrence of hospital readmission after initial discharge.
Days alive and free of hospitalisation Through study completion, an average of 30 days. The total number of calendar days of which a patient is alive and not hospitalized.
Days alive and free of vasopressor and/or inotrope Through study completion, an average of 30 days. The total number of calendar days of which a patient is alive and not requiring vasopressor or inotrope support.
AUC mSOFA score During the treatment period. 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).
Trial Locations
- Locations (1)
Research Site
🇬🇧London, United Kingdom
Research Site🇬🇧London, United Kingdom