A Study Looking at the Use of Biomarkers to Provide Early Indication of Acute Kidney Injury in Patients With Sepsis (Limiting AKI Progression In Sepsis)

Study Overview
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Brief Summary
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Biomarkers that provide an early indicator of kidney stress could be useful in clinical practice to detect silent episodes of acute kidney injury (AKI) or for early identification of subjects at risk of AKI. Two urinary biomarkers have been identified as early indicators of AKI. The NephroCheck® test is a commercially available test that uses these biomarkers, and this study assesses the use of these in reducing negative clinical outcomes for patients with sepsis-associated AKI. The study will enroll subjects diagnosed with sepsis, including septic shock, who will be randomly assigned to either receive NephroCheck®-guided kidney-sparing and fast-tracking interventions; or to receive current Standard of Care assessment and treatment. NOTE: Participants are no longer being recruited to this study.

Official Title
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Limiting AKI Progression In Sepsis (LAPIS): A Phase 4, Multicenter, Randomized Controlled Trial of Biomarker-guided Delivery of Kidney-sparing Care Measures in Sepsis Subjects at Risk of Developing AKI

Conditions
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Acute Kidney Injury, Septic Shock, Sepsis

Intervention / Treatment
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* Device: Subject management guided by NephroCheck® test
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of sepsis or septic shock. Admission to the ICU or planned admission to the ICU with an expected stay of 72 hours or more after enrollment in the same hospital. Expected to have indwelling urinary catheter placed and kept until at least 48 hours after enrollment. Written informed consent. Exclusion Criteria: Women with known pregnancy, prisoners or institutionalized individuals. Previous renal transplant. Stage 2 or 3 Acute Kidney Injury (AKI) at screening. Receiving dialysis (either acute or chronic), or in imminent need of dialysis at enrollment. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Known End Stage Renal Disease (ESRD) or history of active nephrotic syndrome within the last 3 months. Known Stage 2-3 AKI within last 2 weeks. Terminally ill (defined as expectation of death within 6 months), has a do not resuscitate order that would restrict protocol-required procedures, or is being admitted only for palliative care. History of solid organ transplant and receiving calcineurin inhibitors. Documented serious allergy (i.e. anaphylaxis) to vancomycin, aminoglycosides, penicillins, or cephalosporins (intravenous or oral). Known current serum total bilirubin > 4mg/dL. Subjects already included in an observational study can be co-enrolled in LAPIS. Subjects already included in an interventional study may be enrolled with pre-approval of the sponsor according to the following rules: Co-enrollment in LAPIS will not be allowed with investigational drug and device studies; Studies may be allowed if AKI or kidney function is not an endpoint with pre-approval of the LAPIS sponsor; Co-enrollment in LAPIS will not be allowed if co-enrollment is an exclusion criterion in the other study. Subjects with laboratory confirmed COVID-19 infection as the primary reason for hospital admission. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NephroCheck-guided interventions<br> | Device: Subject management guided by NephroCheck® test<br>* NephroCheck® is a device using biomarkers to identify subjects at risk of sepsis-associated acute kidney injury<br>|
| Active Comparator: Standard of Care<br>Standard of Care assessment and treatment | Other: Standard of Care<br>* Standard of Care patient management<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of deaths, dialysis or progression of AKI | Measured by composite number of deaths, dialysis or progression of AKI. Dialysis defined as any form of renal replacement therapy (RRT); progression of AKI defined as Stage 0 to 2/3 or Stage 1 to 3. | Enrollment to 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with progression of AKI | Progression of AKI (Acute Kidney Injury) to Stage 2 or 3 during the time frame. Measured independently. | Enrollment to 48 and 72 hours | 
| Number of deaths | Number of deaths. Measured independently. | Enrollment to 48 and 72 hours | 
| Number of participants receiving dialysis | Dialysis defined as any form of renal replacement therapy (RRT). Measured independently. | Enrollment to 48 and 72 hours | 
| Number participants at Stage 2 or 3 AKI | Defined as highest stage of AKI during the time frame | Enrollment to 72 hours | 
| ICU length of stay |  | Enrollment to hospital discharge or Day 60, whichever is sooner | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Kidney Injury, Sepsis, Kidney damage, Septic shock, Biomarkers