Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03034876 |
| Other study ID # |
4399-Ped-16 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
January 25, 2017 |
| Last updated |
January 25, 2017 |
| Start date |
March 1, 2017 |
| Est. completion date |
December 2017 |
Study information
| Verified date |
January 2017 |
| Source |
Aga Khan University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Acute Kidney Injury is common in critically ill children and is associated with high
morbidity and mortality in pediatric intensive care unit. The serum creatinine is still a
gold standard test for diagnosis of AKI, but it rises after 1 to 3 days of injury . However,
Neutrophil Gelatinase-Associated Lipocalcin (NGAL) is an emerging biomarker in identifying
AKI at an early stages, which may in future help us in promptly instituting reno-protective
interventions like avoidance of nephrotoxic exposure and contrast agents, maintenance of
euvolemia and perfusion pressure which will not only preventing kidney from further failing,
decrease the use of very expensive and complicated renal supportive therapy like continuous
renal replacement therapy (CRRT) as well as in decreasing morbidity and mortality related to
AKI.
Description:
Introduction:
Acute kidney injury (AKI) is complex disorder affecting the millions of children around the
world where approximately 46% of critically ill individual developed acute kidney injury
every year (1, 2). An annual incidence of 3.3 cases/100,000 children along with hospital
mortality rate of up to 25-50% have reported from developed countries (3) This is even high
for developing countries, where annual incidence is 30-50% (4, 5). Furthermore, acute kidney
injury leads to significant healthcare use, with cost estimated between 8 billion dollars
(4). An early diagnosis is the key to prevent morbidity and mortality related to AKI.
The diagnosis of AKI depends upon elevated serum creatinine level or decrease in urine
output . Early detection of AKI is essential. The currently use creatinine clearance (CrCl)
is calculated through Schwartz formula. The level of serum creatinine is poor marker for
early diagnosis. Because it varies with age, gender, hydration and muscle mass and
metabolism. Creatinine never rise until >50% of renal function lost, amount of tubular
secretion overestimate at lower GFR, and in acute changes in GFR. During acute changes of
GFR in AKI, serum creatinine doesn't accurately depict kidney function until steady state
equilibrium has been achieved, which may require several days. There are some biomarker,
with high sensitivity and specificity, which can be used as a tool for early detection of
AKI, and prevent the burden of mortality and morbidity in intensive care unit (6, 7).
Neutrophil gelatinase-associated Lipocalcin (NGAL) recently identified as one of robust
marker in AKI (8). Several published reports that plasma NGA is raised in acute kidney
injury before rise in serum creatinine (9). A Study conducted by Mishra et al, in US showed
that the 2 hours sensitivity is 70% and specificity 94% for NGAL to predict AKI (10). A
developed country data showed 84% and 79% sensitivity , and 96% and 90% specificity of NGAL
to predict the AKI (2, 11) , (see Annexure 1) . However, there is scarce of information
available as plasma NGAL is an early diagnostic marker from Pakistan.
Rationale:
We know that serum creatinine is a gold standard for diagnosis of AKI it is cheaper test to
diagnose , but it rises after 1 to 3 days of injury . However, NGAL is a relatively costly
test but an emerging biomarker in identifying AKI at an early stages, which may in future
help us in promptly instituting reno-protective interventions like avoidance of nephrotoxic
exposure and contrast agents, maintenance of euvolemia and perfusion pressure which will not
only preventing kidney from further failing, decrease the use of very expensive and
complicated renal supportive therapy like continuous renal replacement therapy (CRRT) as
well as in decreasing morbidity and mortality related to AKI.
Objective:
To determine the diagnostic accuracy of serum neutrophil gelatinase-associated Lipocalcin
(NGAL) , in detection of acute kidney injury by comparing creatinine clearance which is gold
standard , in pediatric intensive care unit of Aga khan university hospital Karachi .
Methods:
We will be conducting a prospective observational study in a closed
multidisciplinary-cardiothoracic Pediatric Intensive Care Unit (PICU) of Aga Khan University
Hospital after approval of Ethical Review Committee.
Operational Definition:
Acute Kidney Injury (AKI): AKI is diagnosed according to pediatric RIFLE criteria. Pediatric
RIFLE criteria stratifies AKI when eCrCl decreased by 25 % in first 48hours of PICU.
Shock: Shock is defined by use of vasoactive-inotropic support for at least more than 12
hours to maintain hemodynamics of acutely ill children in PICU for this study.
Neutrophil gelatinase-associated Lipocalcin (NGAL): NGAL is biomarker is measured
quantitatively by a rapid , non - competitive Fluorescence Immunoassay (12) . Level of more
than 150 mg/dl will be considered as a positive for diagnosis of AKI.
Sample Size Calculation:
If prevalence of AKI in children with shock is 46%, the sensitivity and specificity of
plasma NGAL is 0.9 and 0.79 respectively and margin of error is 0.1%, the sample size will
be 140 participants.
Participants:
- Inclusion Criteria: All children with either gender aged of 1 month - 16 years who
required vasoactive-inotropic drugs on admission and stayed for more than 48 hours in
PICU of tertiary care unit of Aga Khan University Hospital, Karachi.
- Exclusion Criteria: All those children who with chronic kidney disease or previous
history of renal injury will be excluded
Study Protocol:
The participants who fulfill inclusion and exclusion criteria of the study will be enrolled
by daily surveillance of PICU. The informed consent will be obtained from parents or legal
guardian. The amount of blood about 1/3rd tea spoon ( 1.5ml ) will be collected from already
existing central line without any extra prick of participants at three different time
interval of 0 , 12 and 48 hours for plasma-NGAL and serum creatinine test in PICU. Then
samples will be sent to main laboratory of our hospital . Blood tests ( NGAL and Serum
Creatinine ) expenses will be paid from approved grant of University Research Council .
Serum NGAL is measured quantitatively by a rapid , non - competitive Fluorescence
Immunoassay (12) . The Triage® NGAL test is a point - of - care , fluorescence - based
immunoassay used in conjunction with the Triage Meter (Biosite Inc . ) for the rapid
quantitative measurement of NGAL concentration. The serum creatinine will be measured by
Jafe's method on ADVIA 1800 Chemistry System (Siemens Healthliners, Germany) , and then
creatinine clearance will be calculated by modified Schwartz formula . (19)
Data Collection:
Data variables will be collected on a structured case report form which included demographic
variables (age, gender, weight, height), clinical and laboratory variables like admission
diagnosis, comorbidities, severity illness score (PRISM III score), use of vasoactive drugs,
mechanical ventilation, urine output, fluid balance, serum creatinine and plasma NGAL. The
discharge status as alive vs. expired, length of mechanical ventilation and hospitalization
and use of renal supportive therapy like peritoneal dialysis will also recorded on case
report form.
Outcome:
The primary outcome of this study is to evaluate the level of plasma NGAL in children who is
in shock with and without AKI according to RIFLE criteria.
Statistical Analysis:
Data will be entered and analyzed into SPSS V20 (SPSS Inc. Chicago, IL).Normally distributed
continuous variables will be reported as mean with standard deviation (SD) and will be
compared with student's test. Non-normally continuous distributed data will be reported as
medians with interquartile range (IQR) and will be compared with Man Whitney test and
Kruskal Wallis test. The categorical data will be reported as proportion and will be
compared as Fischer's exact test or Chi-square test. The association between variables will
be assessed by Spearman rank order correlation analysis. The diagnostic accuracy of plasma
NGAL to predict AKI in children with shock will be defined by calculation of Area Under
Curve (AUC) of Receiving Operating Characteristics (ROC) Curves. An AUC of 0.5 is no better
than by chance, whereas a value of 1.0 indicates a perfect biomarker. A p-value of <0.05 was
considered as statistically significant.
Ethical Consideration:
All data variables will be stored in a password protected computer and strict
confidentiality will be maintained.
