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) (LAPIS)

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

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.

Study Overview

• Status: Terminated
• Conditions: Sepsis; Septic Shock; Acute Kidney Injury
• Intervention / Treatment: Device: Subject management guided by NephroCheck® test; Other: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Hôpital Erasme, Soins Intensifs, Route de Lennik 808
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • AZ Sint-Jan Brugge-Oostende, Intensieve Zorgen, Ruddershove 10
• France
  • Dijon, France, 21079
    • CHRU Dijon Complexe Du Bocage, Department Infectiologie, 14 rue Gaffarel
  • Paris, France, 75679
    • Hopital Cochin, 27 Rue Du Faubourg Saint Jacques
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49100
      • CHU Angers, 4 Rue Larrey
  • Pas-de-Calais
    • Béthune, Pas-de-Calais, France, 62408
      • Centre Hospitalier de Béthune, Service de Réanimation et Surveillance continue, 27 rue Delbecque
• Germany
  • Münster, Germany, 48149
    • Universitatsklinikum Munster, Albert-Schweitzer-Campus 1
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • University Clinic Heidelberg, Klinik für Anaesthesiologie, Im Neuenheimer Feld 110
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitatsklinikum Leipzig, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Liebigstraße 20
• United States
  • Louisiana
    • Shreveport, Louisiana, United States, 71130
      • LSU Health Sciences Center, 1541 Kings Highway
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital, 75 Francis Street
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center, 1275 York Avenue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Co-enrollment in LAPIS will not be allowed with investigational drug and device studies;
  2. Studies may be allowed if AKI or kidney function is not an endpoint with pre-approval of the LAPIS sponsor;
  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BioMérieux
• Investigators: Principal Investigator: Hernando Gomez, MD, MPH, Center for Critical Care Nephrology, University of Pittsburgh Medical Center

Publications and helpful links

General Publications

• Molinari L, Heskia F, Peerapornratana S, Ronco C, Guzzi L, Toback S, Birch R, Beyhaghi H, Kwan T, Kampf JP, Yealy DM, Kellum JA; Sapphire and Protocolized Care for Early Septic Shock (ProCESS) Investigators. Limiting Acute Kidney Injury Progression In Sepsis: Study Protocol and Trial Simulation. Crit Care Med. 2021 Oct 1;49(10):1706-1716. doi: 10.1097/CCM.0000000000005061.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Actual): February 14, 2022
• Study Completion (Actual): February 14, 2022

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Septic shock; Biomarkers; Sepsis; Acute Kidney Injury; Kidney damage
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Shock; Sepsis; Toxemia; Shock, Septic; Acute Kidney Injury
• Other Study ID Numbers: LAPIS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes