Nephroprotection in Severe Trauma Patients With Kidney Stress (NephroTrauma)

Impact of a Nephroprotection Bundle-of-care in Severe Trauma Patients at Risk of Acute Kidney Injury: a Multicenter Randomized Controlled Trial

Acute Kidney Injury (AKI) occurs in 24% of trauma patients, and is even more common in those with severe trauma. It is a major contributor to morbidity and mortality in trauma. Diagnosis of AKI is based on elevated serum creatinine and decreased urine output, two functional markers already indicating the presence of a significant kidney function impairment. Earlier detection of kidney stress, at a preclinical stage when cellular modifications are still reversible, could reduce the occurrence of AKI episodes if nephroprotective measures are rapidly implemented.

Several randomized controlled trials have shown that early implementation of such a nephroprotection bundle-of-care in patients at risk of AKI after major surgery reduces the incidence of severe AKI within 72 hours. Although its use is supported by international guidelines, this nephroprotection bundle-of-care is rarely implemented in its totality, due to the significant financial and human resources required for its full implementation.

The Nephrocheck® (NC) test is a urine test for which a result > 0.3 is predictive of AKI development. It might enable early identification of trauma patients at risk of AKI, so that implementation of the nephroprotection bundle-of-care could be targeted solely at those high-risk patients.

Thus, the investigators hypothesize that in a population of severe trauma patients (ISS score>15) at risk of AKI (defined by a NC on Intensive Care Unit (ICU) admission > 0.3), early implementation of a nephroprotection bundle-of-care would reduce the risk of AKI occurring within 3 days of ICU admission, compared with standard-of-care management. This study will compare the occurrence of AKI in these two groups in a multicenter randomized controlled trial.

Study Overview

• Status: Recruiting
• Conditions: Trauma; Complications
• Intervention / Treatment: Other: Standard-of-care; Other: Systematic nephroprotection bundle-of-care

• Study Type: Interventional
• Enrollment (Estimated): 523
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karine POYAU; Phone Number: +33 04 72 11 53 81; Email: karine.poyau@chu-lyon.fr
• Study Contact Backup: Name: Céline MONARD; Phone Number: +33 04 72 11 13 27; Email: celine.monard@chu-lyon.fr

Study Locations

• France
  • Clermont-Ferrand, France, 63100
    • Not yet recruiting
    • Centre Hospitalier universitaire Estaing, Service anesthésie-réanimation
    • Contact: Benjamin RIEU, MD; Phone Number: +33 04 73 75 05 06; Email: brieu@chu-clermontferrand.fr
    • Principal Investigator: Benjamin RIEU, MD
  • La Tronche, France, 38700
    • Not yet recruiting
    • Centre hospitalier universitaire de Grenoble Alpes, Pôle anesthésie-réanimation
    • Contact: Thibaut TROUVE-BUISSON, MD; Phone Number: +33 04 76 76 52 95; Email: ttrouvebuisson@chu-grenoble.fr
    • Principal Investigator: Thibaut TROUVE-BUISSON, MD
  • Lyon, France, 69003
    • Recruiting
    • Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'anesthésie-réanimation
    • Contact: Céline MONARD, MD; Phone Number: +33 04 72 11 13 27; Email: celine.monard@chu-lyon.fr
    • Principal Investigator: Céline MONARD, MD
  • Pierre-Bénite, France, 69310
    • Recruiting
    • Hospices Civils de Lyon, Hôpital Lyon-Sud, Service d'anesthésie-réanimation
    • Contact: Jean-Stéphane DAVID, MD, PhD; Phone Number: +33 04 78 86 57 56; Email: jean-stephane.david@chu-lyon.fr
    • Principal Investigator: Jean-Stéphane DAVID, MD, PhD
  • Saint-Étienne, France, 42000
    • Not yet recruiting
    • Centre hospitalier universitaire de Saint Etienne, Hôpital Bellevue, Service anesthésie-réanimation
    • Contact: Jérôme MOREL, MD, PhD; Phone Number: +33 04 77 82 83 29; Email: jerome.morel@chu-st-etienne.fr
    • Principal Investigator: Jérôme MOREL, MD, PhD
  • Épagny, France, 74370
    • Not yet recruiting
    • Centre hospitaler Annecy Genevois, Service de réanimation
    • Contact: Albrice LEVRAT, MD; Phone Number: +33 04 50 63 60 30; Email: alevrat@ch-annecygenevois.fr
    • Principal Investigator: Albrice LEVRAT, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patient (≥ 18 years)
• Severe trauma patients (ISS score > 15) admitted to a trauma center
• Time between trauma and admission to trauma center <6h
• Patient with indwelling urinary catheter
• High risk of AKI: measurement of NC score on fresh urine performed as soon as possible within 12 hours of admission to ICU and value > 0.3.
• Affiliated with a social security scheme or beneficiary of a similar scheme
• Consent signed by patient or close relative, or attestation signed by investigator in case of emergency

Exclusion Criteria:

• Adult under legal protection (guardianship, curators)
• Persons deprived of their liberty by judicial or administrative decision
• Patients taking part in other interventional research which may interfere with the research and which includes an exclusion period still in progress at the time of inclusion.
• Pregnant or breast-feeding woman (diagnosis of pregnancy by plasma βHCG (Beta-Human Chorionic Gonadotropin) assay routinely performed as part of the blood test on admission to the outpatient department of a woman of childbearing age).
• Patients with end-stage or severe chronic renal failure with Glomerular Filtration Rate (GFR) < 30 milliliters/min/1.73m2 or chronic dialysis.
• Anuric patients
• Severe heart failure defined as Left Ventricular Ejection Fraction (LVEF) <25%.
• Patient moribund on admission with an estimated length of stay of less than 24 hours
• Patient with AKI at time of randomization (developed prior to ICU admission or within the first 12 hours of ICU admission, before randomization).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Observational group; Patients in the observational group will be managed according to the unit's standard-of-care, as in the control group, but without investigators knowing the patient's risk of AKI (NC score not known)	Other: Standard-of-care; Management according to current ICU practices
Other: Control group: Standard-of-care; Patients at risk of AKI (NC>0.3) randomized in the control group will be managed according to the unit's standard-of-care.	Other: Standard-of-care; Management according to current ICU practices
Experimental: Intervention group: nephroprotection bundle-of-care; Patients at risk of AKI (NC>0.3) randomized in the intervention group will receive the systematic and complete application of a nephroprotection bundle-of-care for three days following ICU admission.	Other: Systematic nephroprotection bundle-of-care; The nephroprotection bundle-of-care includes 5 components: Prevention of drugs' nephrotoxicity; Hemodynamic optimization, for 24h; Blood glucose control and avoidance of hyperglycemia; Early detection of rhabdomyolysis; Monitoring of renal function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients developing an AKI episode within 3 days after ICU admission.	AKI will be defined according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria, either by a drop in urine output (oliguria < 0.5ml/kg/h for 6h) and/or a rise in serum creatinine (1.5x baseline or increase of 26.5 µmol/l).	During 3 days from ICU admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with AKI within 7 days of ICU admission	AKI will be defined according to KDIGO criteria, either by a drop in urine output (oliguria < 0.5ml/kg/h for 6h) and/or a rise in serum creatinine (1.5x baseline or increase of 26.5 µmol/l).	During 7 days from ICU admission
Proportion of patients with severe AKI within 3 days of ICU admission	Severe AKI is defined as AKI stage 2 or 3 according to KDIGO criteria	During 3 days from ICU admission
Proportion of patients with severe AKI within 7 days of ICU admission	Severe AKI is defined as AKI stage 2 or 3 according to KDIGO criteria	During 7 days from ICU admission
Proportion of patients with MAKE (MAjor Adverse Kidney Event) 28	MAKE 28 is defined by the occurrence of one event among (1) death before day 28 after ICU admission, (2) requirement of renal replacement therapy on day 28 or (3) incomplete renal recovery on day 28.	At 28 days after ICU admission
Proportion of patients with a complication among cardiovascular and hemodynamic complications; septic complications; hemorrhagic complications within 7 days after ICU admission	Cardiovascular or hemodynamic complications include ventricular cardiac rhythm disorders, cardiogenic acute pulmonary edema and poorly controlled arterial hypertension [MAP (Mean Arterial Pressure) > 120 mmHg for 4 hours]. Septic complications correspond to sepsis defined by the association of an infection and an increase in SOFA >=2. Hemorrhagic complications are defined by the number of packed red blood cells (RBCs) used.	During 7 days after ICU admission.
Proportion of patients with at least one episode of dysglycemia within 3 days after ICU admission	Episodes of dysglycemia are defined as hypoglycemia (<4mmol/l) or hyperglycemia (>12mmol/l).	During 3 days after ICU admission.
ICU and hospital length-of-stay	Total number of days spent in critical care (intensive care, continuous care) and in the initial hospital	During 28 days from ICU admission
Identification of risk factors for AKI in trauma patients using clinical and laboratory parameters	Known and novel risk factors for AKI in trauma patients will be evaluated using clinical variables (e.g., age, comorbidities, injury severity scores), hemodynamic parameters (e.g., MAP, lactate), and biomarkers of kidney function (e.g., CPK, TIMP-2/IGFBP-7)	During 7 days from ICU admission
Incidence of AKI in trauma patients within 3 days of ICU admission based on KDIGO Criteria	The incidence of all stages and severe AKI in trauma patients at risk will be assessed based on the KDIGO criteria	During 3 days after ICU admission
Characterization of AKI episodes phenotype in trauma patients using KDIGO criteria	Acute Kidney Injury episodes will be characterized based on a combination of factors including : Time to AKI onset: defined as the time (in hours) from ICU admission to the diagnosis of AKI; Diagnostic criteria: whether the AKI is diagnosed based on serum creatinine or urine output changes; Severity: the highest KDIGO stage (1, 2, or 3) reached during the episode; Duration: transient (<48h) or persistent (≥48h) AKI.	During 7 days from ICU admission
Proportion of patients receiving the nephroprotection bundle-of-care in its entirety, by component, and by practice.	The entirety of the nephroprotection bundle-of-care is defined by the combination of at least one practice from each component: medication, hemodynamics, rhabdomyolysis, monitoring, glycemia	During 3 days after ICU admission
Cost-effectiveness incremental ratio of the nephroprotection bundle-of-care compared with standard-of-care at 7 days after ICU admission.	The incremental cost-effectiveness ratio will be expressed as the additional cost per AKI avoided.	At 7 days after ICU admission
Cost-effectiveness incremental ratio of the nephroprotection bundle-of-care compared with standard-of-care at 28 days after ICU admission.	The incremental cost-effectiveness ratio will be expressed as the additional cost per AKI avoided.	At 28 days after ICU admission
Average costs of initial hospital stay for each group		During 28 days after ICU admission

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Céline MONARD, Hospices civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Biomarker; Acute Kidney Injury; Severe trauma; Nephroprotection bundle-of-care
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: 69HCL21_1435; 2022-A01052-41 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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