2025-522232-13-00招募中2 期
A Phase IIa, Randomised, Double-blind, Placebo-controlled, Multicentre Study to Assess the Efficacy, Safety, and Tolerability of AZD4144 in Participants with Sepsis-associated Acute Kidney Injury (SERENIA)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Area Under the Curve (AUC) of 24-hour Creatinine Clearance (CrCl)
研究概览
简要总结
To evaluate the effect of AZD4144 on Creatinine Clearance (CrCl)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Adults aged 18 to 80 years
- •Hospitalized with a diagnosis of sepsis (suspected or confirmed) within 7 days of admission
- •Diagnosis of acute kidney injury (AKI; KDIGO Stage ≥ 1) within 72 hours of sepsis diagnosis.
- •Able to receive the study drug within 36 hours of SA-AKI diagnosis.
- •Provision of informed consent by the participant or legally authorized representative.
- •Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on: (a) Suspected or confirmed bacterial infection AND (b) Acute increase of mSOFA score of 2 or more excluding renal component (change in score measured to account for participants that may meet mSOFA criteria from pre-existing organ dysfunction before the onset of infection).
- •Vasopressor and/or inotrope therapy for sepsis-induced hypotension (norepinephrine [noradrenaline], epinephrine [adrenaline], phenylephrine, dopamine, dobutamine) for ≥ 4 hours after 30 mL/kg or clinically appropriate volume resuscitation prior to randomisation
- •Diagnosis of AKI with modified KDIGO Stage ≥ 1 persisting after initial volume resuscitation (30 mL/kg or as clinically indicated per investigator discretion)
- •Outpatient pre-AKI reference eGFR ≥ 30 mL/min/1.73 m2 or admission pre-AKI reference eGFR ≥ 45 mL/min/1.73 m2.
排除标准
- •Known history of Stage 4 or 5 CKD with documented sustained eGFR < 30 mL/min/1.73 m2 prior to hospital admission.
- •Known history of cerebrovascular accident within the last 90 days.
- •Known history of heart failure with reduced ejection fraction with documented ejection fraction ≤ 20% before sepsis diagnosis.
- •Known hypersensitivity to iohexol or known history of severe adverse reaction to iodinated contrast media.
- •Current KRT (eg, continuous haemofiltration and haemodialysis/continuous renal replacement therapy, intermittent haemodialysis, and peritoneal dialysis) or planned KRT at randomisation.
- •Active or planned treatment of sepsis with an extracorporeal haemoperfusion device.
- •Participation in any other concurrent ICU which could impact participant clinical outcomes and confound results of this study to, including but not limited to volume resuscitation, vasopressor, or mechanical ventilation studies.
- •Presence of anuria (≥ 12 hours) at randomisation
- •Known history of ST-elevation myocardial infarction or non-ST-elevation myocardial infarction, with or without intervention by percutaneous coronary intervention or coronary artery bypass grafting within the last 90 days.
- •Undergoing extracorporeal membrane oxygenation (ECMO) at randomisation.
- •Neutropenia: ANC < 1.5 × 109/L.
- •No serum creatinine results available within 12 months of admission and an eGFR < 45 mL/min/1.73 m2 at admission.
- •Admitting diagnosis of rhabdomyolysis.
- •Admitting diagnosis of trauma with CK > 15000 U/L.
- •Presumed nidus of infection in central nervous system.
- •First dose of IMP unable to be administered within 36 hours of AKI diagnosis.
- •Presence of a do-not-resuscitate order.
- •Sepsis diagnosed > 7 days after hospital admission (to include from time of outside admission if patient transferred from another healthcare setting).
- •AKI attributed to causes other than sepsis, including but not limited to compromised renal perfusion-related causes (surgical complication, acute abdominal aortic aneurysm, dissection, renal artery stenosis, etc), glomerular disease, acute interstitial nephritis, and medication toxicity.
- •Evidence of recovery from AKI prior to randomisation defined as: (a) A reduction of serum creatinine to less than 1.5 times reference serum creatinine in the last available local SoC laboratory result before randomisation or (b) A > 25% reduction in serum creatinine from peak serum creatinine after volume resuscitation prior to randomisation.
- •Expected survival from sepsis < 24 hours.
- •Expected survival < 90 days due to chronic or pre-existing medical conditions other than SA-AKI, including but not limited to cancer, end-stage cardiac disease, cardiac arrest requiring cardiopulmonary resuscitation or with pulseless electrical activity or asystole within the past 30 days, end-stage lung disease, end-stage neurological disease, and end-stage liver disease.
- •Known history of immunodeficiency disease or currently receiving immunosuppressant therapy for non-sepsis related disease, including but not limited to treatment for organ transplant, cancer, or autoimmune disease; current treatment with high-dose steroid therapy (dose equivalent to prednisone/prednisolone 0.5 mg/kg/day) exceeding 2 weeks duration. Steroids administered as management of septic shock are permitted.
- •Sepsis attributed to confirmed or presumed fungal or viral infection at time of Screening. Concomitant bacteraemia with a viral infection is NOT exclusionary (for example presumed bacteraemia in a participant with documented influenza).
结局指标
主要结局
Area Under the Curve (AUC) of 24-hour Creatinine Clearance (CrCl)
Area Under the Curve (AUC) of 24-hour Creatinine Clearance (CrCl)
次要结局
- Days alive and free of KRT
- Days alive and free of modified KDIGO AKI Stage 2 or 3
- AUC: Serum creatinine, Serum cystatin C, mGFR
- Cmax/Cbaseline: Serum creatinine, Serum cystatin C
- AUC: Plasma and urine IL-18, Plasma and urine IL-6
- Plasma concentrations of AZD4144
- Occurrence of any of the following MAKE30 components: (a) Decrease from pre-AKI reference eGFR of ≥ 25% (b) Initiation of KRT at any time (c) Death from any cause
- Days alive and free of mechanical ventilation
- Days alive and outside of the ICU
- Rehospitalisation
- Days alive and free of hospitalisation
- Days alive and free of vasopressor and/or inotrope use
- AUC mSOFA score
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (4)
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