NGAL As An Aid for the Diagnosis of Acute Kidney Injury in Intensive Care

Acute Kidney Injury Clinical Trial

Official title:

The NGAL Test™ As An Aid for the Diagnosis of AKI in an Intensive Care Population, US

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02121470
• Other study ID #: KLIN 12-005
• Status: Completed
• Phase: N/A
• First received: April 22, 2014
• Last updated: August 10, 2015
• Start date: February 2014
• Est. completion date: June 2015

Study information

• Verified date: August 2015
• Source: BioPorto Diagnostics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

Acute Kidney Injury (AKI) is a common and severe complication in critically ill patients which is associated with increased morbidity and mortality as well as high costs of medical care.

NGAL (neutrophil gelatinase-associated lipocalin, lipocalin-2, siderocalin) is a biomarker, that is expressed in several tissues including the kidneys. Renal expression of NGAL is dramatically increased in kidney injury from a variety of causes, and NGAL is released into both urine and plasma. NGAL levels rise within two hours of the insult, making NGAL an early and sensitive biomarker of kidney injury, with the potential to assist clinicians in managing patients at risk of kidney injury.

This study is designed to validate the assigned NGAL cutoff value by comparing to clinical diagnosis of AKI as determined by current clinical practice in the US.

The study sites will enroll consecutive ICU patients. Patients are given standard clinical care and lab-work. Each day, one additional urine and two additional plasma samples will be drawn and frozen. These additional samples are shipped to Sponsor for retrospective NGAL measurements.

The duration of each subject´s participation will be until discharge from the ICU, or for a maximum 8 days, whichever comes first. In addition serum creatinine values will continue to be collected manually from the hospital data system for 48 hours after discharge from the ICU. (If subject has been in ICU for 8 or more days, the follow up values are collected while the patient is still in the ICU).

250 subjects will be enrolled in total at the three investigator sites. At least 40 patients must be enrolled at each site.

The NGAL value will be matched to the "clinical diagnosis" of acute kidney injury (AKI) as specified by KDIGO® guidelines. The clinical diagnosis will be assigned by a three-person adjudication panel based on the entries in the eCRF by the investigators. Adjudicators are blinded for investigation site, AKI-diagnosis by treating physician, and NGAL values.

A comparison of AKI diagnosis based on the cutoff value 250 ng/mL and clinical diagnosis as assigned by the majority of the adjudication panel will be conducted.

Description:

AKI is a common and severe complication in critically ill patients, which is associated with increased morbidity and mortality as well as high costs of medical care.

Despite efforts to standardize the definition and classification of AKI, there is still inconsistency in the application of the criteria and the limitations of serum creatinine and urine output for detecting AKI is generally recognized by the medical community. In the future, biomarkers of renal cell injury may identify additional patients with AKI and may identify the majority of patients at an earlier stage.

NGAL (neutrophil gelatinase-associated lipocalin, lipocalin-2, siderocalin) is such a biomarker. It is a small protein expressed in neutrophils and certain epithelia, including the renal tubules. Renal expression of NGAL is dramatically increased in kidney injury from a variety of causes, and NGAL is released into both urine and plasma. NGAL levels rise within two hours of the insult, making NGAL an early and sensitive biomarker of kidney injury.

Due to the heterogeneous implementation of AKI definitions and classifications, a uniform definition will be applied to this investigation, to ensure comparative results between the enrollment sites.

The aim of the study is to validate the assigned NGAL cutoff value by comparing to clinical diagnosis of AKI as determined by current clinical practice in the US.

The study sites will enroll consecutive patients meeting the criteria below in an ICU or critical care setting. Patients are given standard clinical care and lab-work. Each day, one additional urine and two additional plasma samples will be drawn and frozen. These additional samples are shipped to Sponsor for retrospective NGAL measurements.

The duration of each subject´s participation will be until discharge from the ICU, or for a maximum 8 days, whichever comes first. In addition serum creatinine values will continue to be collected manually from the hospital data system for 48 hours after discharge from the ICU. (If subject has been in ICU for 8 or more days, the follow up values are collected while the patient is still in the ICU).

250 subjects will be enrolled in total at the three investigator sites. At least 40 patients must be enrolled at each site.

The NGAL value will be matched to the "clinical diagnosis" of acute kidney injury (AKI) as specified by KDIGO® guidelines. The clinical diagnosis will be assigned by a three-person adjudication panel based on the entries in the eCRF by the investigators. Adjudicators are blinded for investigation site, AKI-diagnosis by treating physician, and NGAL values.

A comparison of AKI diagnosis based on the cutoff value 250 ng/mL and clinical diagnosis as assigned by the majority of the adjudication panel will be conducted.

Primary endpoints:

• Sensitivity of the NGAL test will be estimated as the proportion of patients with an observed NGAL value above or equal to 250 ng/ml among patients classified as having AKI, and.

• Specificity of the NGAL test will be estimated as the proportion of patients with an observed NGAL value below 250 ng/ml among patients classified as not having AKI

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Admission to intensive care unit

• Informed consent

• Age = 18 years.

Exclusion criteria:

• History of nephrectomy, renal transplantation and/or renal replacement therapy initiated before admission

• Males and females aged 17 years or below

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Kidney Injury

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Methodist Hospital	Houston	Texas
United States	Baystate Medical Center / WNERTA	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
BioPorto Diagnostics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NGAL (ng/mL)	Highest measured value used	Daily during ICU stay up to 8 days	No
Secondary	Creatinine	Change from baseline/reference value calculated to be used in application of diagnostic AKI criteria and rating	Daily during ICU stay up to 8 days + 2 days after discharge	No
Secondary	Urine output	Urine output calculated (mL/kg/h) to be used in application of diagnostic AKI criteria and rating	6h, 12h and 24h daily during ICU stay up to 8 days	No