AWARE: Observational Study of Pediatric Acute Kidney Injury, Risk Factors and Outcomes

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Completed

CT.gov ID

NCT01987921

Collaborator

(none)

5,237

Enrollment

Locations

Duration (Months)

163.7

Patients Per Site

14.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pediatric acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. Currently, understanding of the epidemiology and diagnosis of AKI in children is limited by single center retrospective data and inconsistent diagnostic and stratification criteria. The hypotheses of the AWARE study is that 1) renal angina, a composite of early injury signs and risk of disease, will predict severe subsequent AKI in critically ill children and 2) the incorporation of urinary biomarkers into the renal angina scoring system will improve the prediction of the severe injury. The AWARE study is conducted to describe AKI epidemiology in a heterogeneous multinational cohort of critically ill children, characterize AKI risk factors and associated morbidity, and validate the KDIGO AKI criteria as a predictor of pediatric AKI outcomes. The multi-center, multi-national registry will create the largest ever repository of information available on AKI in children.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury

Detailed Description

The AWARE study is a multicenter prospective observational study designed to achieve the following three goals:

Establish the first international pediatric AKI registry to describe in detail the epidemiology and outcome of AKI in different pediatric and cardiac ICUs around the world.
Validate the precision of RAI in ruling out AKI in a large, heterogeneous study population.
Evaluate the predictive value of using RAI before and after the incorporation of four different urinary AKI biomarkers used in different combinations.

To achieve these primary goals, children admitted to PICUs and/or pediatric cardiac ICUs from different US and international centers will be screened for enrollment eligibility. Patients admitted to general PICU and non-surgical patients admitted to cardiac ICUs are considered the target population of AWARE. Patients admitted to neonatal ICUs and post-surgical admissions to cardiac ICUs are not included in AWARE. Both clinical variables and urinary biomarkers would be needed to accomplish the analysis.

A- Clinical variables: Clinical data of interest at study entry will include age, gender, race, ethnicity, height, weight, date of ICU admission, date of ICU discharge, date of hospital discharge, admission diagnosis(es) and primary co-morbidities. Creatinine clearance (eCrCl) will be estimated by the modified Schwartz formula29. Baseline creatinine will be collected if the patient had a listed value in the medical record in the 90 days prior to admission, with the lowest value selected if multiple measurements are present. In cases where no baseline data is available, reference eCrCl will be estimated as 120 mL/min/1.73m2. 30

Clinical data will be recorded on admission and on a daily basis for the first seven days of the PICU admission or till discharge from the PICU whatever is earlier. Another set of data will be collected to evaluate the primary and secondary outcomes of the study (see later). The outcomes data will be collected on day 28 after ICU admission when available or by most recent available data before hospital discharge for patients with no available data on day 28.

Clinical parameters of interest include:

use of fluid resuscitation in peri-ICU period ( normal saline, PlasmalyteTM ,Ringer's Lactate, 5% Albumin, starch based fluids including dextran composites)
daily first shift heart rate (beats per minute) from day 1 through day 7 (at the most) of ICU admission
daily first shift respiratory rate (breaths per minute) from day 1 through day 7 (at the most) of ICU admission
daily first shift systolic and diastolic blood pressure and mean arterial pressure (arterial line measurements will be used when available) from day 1 through day 7 (at the most) of ICU admission
daily first shift temperature from day 1 through day 7 (at the most) of ICU admission
use of mechanical ventilation (yes/no)
daily first shift mean airway pressure when applicable from day 1 through day 7 (at the most) of ICU admission
duration of mechanical ventilation
daily first shift oxygen blood saturation ( SpO2) from day 1 through day 7 (at the most) of ICU admission
daily first shift fraction of inspired oxygen (FiO2) (%) from day 1 through day 7 (at the most) of ICU admission
use of nephrotoxins (yes/no) from day 0 through day 7 (at the most) of ICU admission
types of nephrotoxic agents:
Nonsteroidal anti-inflammatory drugs (NSAIDS)
Aminoglycosides,
anti-viral therapy,
Vancomycin,
Piperacillin/Tazobactam,
Calcineurin inhibitors,
IV radio-contrasts ( Including Gadolinium for MRI)
use of vasoactive support (yes/no) from day 0 through day 7 (at the most) of ICU admission
use of diuretics on day 0 and during admission (yes/no)
class of diuretics used (Loop diuretics, Thiazides, Potassium sparing, Carbonic anhydrase inhibitors, Vasopressin antagonist, Osmotic diuretic,)
serum creatinine (SCr) (mg/dl) from 3 months prior to ICU admission through up 28 days after admission
fraction of inspired oxygen (FiO2) (%) from day 1 through day 7 (at the most) of ICU admission
total fluid in (mL) from day 0 through day 7 (at the most of ICU admission)
total fluid out (mL) from day 0 through day 7 (at the most of ICU admission)
total urine output (mL) from day 0 through day 7 (at the most of ICU admission)
urine output per 12-hour shift (mL/hr) from day 0 through day 7 (at the most of ICU admission)
use of renal replacement therapy (RRT) (yes/no)
modality of RRT when available
use of ventricular assisted devices or extracorporeal Membrane Oxygenation (ECMO)
outcome data
mortality
PICU length of stay
hospital length of stay

Calculated daily values include:

Change from baseline creatinine calculated as = Daily Cr/Baseline Cr
AKI stage per Kidney Disease Improving Global Outcomes (KDIGO) guidelines
Stages 1,2 ,3 assessed by both creatinine and urine output (Table-1)31
% Fluid overload: cumulative PICU fluid overload percentage (% FO), calculated as = ((total PICU Fluid in (L) - total PICU fluid out (L)) / PICU admit weight (kg))*100
urine output per kg per 8 hour interval
Renal angina index (RAI) will be assessed on Days 0 and 1.
RAI = composite of risk strata and AKI clinical injury score

o Risk strata (AKI risk tiers):

1 (moderate risk): This stratum include all patients admitted to PICU and not fulfilling the criteria of high risk or very high risk strata
3 (high risk): This include all patients with history of solid organ or bone marrow transplantation (BMT)
5 (very high risk): This include all patients who receive both invasive mechanical ventilatory support AND vasoactive medication at any time in the first 12 hours of ICU admission.

o AKI Clinical Injury scores:

1 (ICU status and no increase from baseline creatinine or <5% fluid overload FO)
2 (> 5% FO or change from baseline creatinine of 1-1.49x)
4 (>10% FO or increase from baseline creatinine of 1.5-1.99x)
8 (>15% FO or increase from baseline creatinine of >= 2x).

RAI = Risk score X Injury Score The range of indices is therefore: 1, 2, 3, 4, 5, 6, 8, 10, 12, 20, 24, and 40. RAI >= 8 indicates fulfillment of renal angina ( Basu et al5)

Urine samples: The collection of urine samples is optional for the participating sites. The urine samples will be collected in the morning between 6 and 10 A.M. and/or in the afternoon between 3 and 7 P.M. for up to four days (day 0 through day 3) on all enrolled patients. Some centers may collect daily urine samples, others may choose to collect samples in both time windows. Urine will be drained only from the collection apparatus of an indwelling urinary drainage system or intermittent catheterization. Patients will not be bagged or catheterized separately/independently for the purposes of this study. Collected urine samples will be kept on ice or in 4° C refrigerator until they are processed. During processing, specimens will be centrifuged at 4°C for fifteen minutes. The supernatant will then be divided into up to nine 1-mL aliquots depending on the collected urine volume and stored at minus 80°C. The stored urine samples from all participating sites will be shipped to the Center for Acute Care Nephrology Biomarker Core Laboratory in the Division of Nephrology and Hypertension at Cincinnati Children's Hospital Medical Center when the coordinating site request the samples to be shipped at the time point set forth by the coordinating site. The shipping supplies and instructions will be provided by the coordinating site.

Study Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

5237 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Assessment of Worldwide AKI in Pediatrics, Renal Angina and Epidemiology

Study Start Date :

Jan 1, 2014

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Pediatric Intensive Care Unit Patients All patients will be included in a single cohort initially (admission to the PICU) and then cohorted into groups based on development of severe AKI (Stage 2-3 KDIGO by either Cr or UOP criteria) within the first seven days, renal angina risk strata, medical admission diagnoses, and outcomes.

Outcome Measures

Primary Outcome Measures

Severe AKI in first seven days of ICU Admission [Within 7 Days of ICU admission]
AKI as defined by KDIGO stage 2 or 3 (by either changes in creatinine or UOP) assessed within 7 days of ICU admission

Secondary Outcome Measures

AKI Conferred Risk on Mortality [28 days]
After adjustment for covariates, will analyze the independent conferred risk on mortality within 28 days of severe AKI (detected within the first seven days of ICU admission).
Comparison of AKI by Creatinine and Urine Output [7 and 28 days]
Epidemiology and AKI outcomes for patients will be separated into diagnosis by changes in creatinine, urine output, or both. Independent associations with AKI diagnosed by urine output and outcome will be identified.
Determination of AKI Progression [7 days]
The stage by stage increase or decrease in AKI severity will be followed - with associations determined - to identify risk factors for AKI progression to severe injury.
Identification of Predictors of Severe AKI [7 days]
Variables with independent associations for increased risk of severe AKI in the first seven days will be identified.

Other Outcome Measures

Increase in pre-test probability of AKI risk using the renal angina index [3-4 days]
Assessing all patients with complete data for the presence of renal angina 12 hours after admission using the renal angina index will allow for determination of the heightened prediction of Day 3 - AKI versus standard methods of severity of illness or changes in creatinine alone.
Biomarker incorporation into renal angina index [3-4 days]
Incorporating values of measured urinary biomarkers, we will determine the additive effect on discriminatory precision for the renal angina index on prediction of Day 3 - AKI

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age greater than 90 days
Age less than 25 years

Exclusion Criteria:

Patients on maintenance hemodialysis, peritoneal dialysis, or with chronic kidney disease with a baseline eGFR of <15 mL/min/1.73m2
Patients with renal transplant received less than 90 days from the ICU admission.
Patients admitted to ICU immediately post-operative to within three months following surgical correction of congenital heart disease.
Patients with uncorrected congenital heart disease. This criteria does not include patients with isolated uncorrected ventricular septal defect (VSD), atrial septal defect (ASD), patent ductus arteriosus (PDA) and patent foramen ovale (PFO).
Patients following cardiac catheterization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35203
2	Stanford University	Palo Alto	California	United States	94305
3	Children's Hospital Colorado	Aurora	Colorado	United States
4	Yale University	New Haven	Connecticut	United States	06510
5	Nemours/Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
6	Emory University	Atlanta	Georgia	United States	30322
7	University of Iowa	Des Moines	Iowa	United States	52242
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503
10	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
11	Washington University in St. Louis	St. Louis	Missouri	United States	63130
12	University of New Mexico	Albuquerque	New Mexico	United States	87131
13	Cohen Children's Medical Center of NY	New Hyde Park	New York	United States	11354
14	Stony Brook Long Island Children's Hospital	Stony Brook	New York	United States	11794
15	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
16	Texas Children's Hospital	Houston	Texas	United States	77030
17	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
18	Virginia Commonwealth University	Richmond	Virginia	United States	23284
19	Children's Hospital at Westmead	Westmead	New South Wales	Australia
20	The Sydney Children's Hospitals Network	Sydney		Australia	NSW 2031
21	University of Edmonton	Edmonton		Canada	AB T6G 2R3
22	Montreal Children's/McGill	Montreal		Canada	QC H3H 1P3
23	University of British Columbia and Children's and Women's Health Center of British Columbia Branch	Vancouver		Canada
24	Nanjing Children's Hospital	Nanjing		China
25	Dept of Child Health Cipto Mangunkusumo/University of Indonesia	Jakarta		Indonesia
26	Dept of Child Health Airlangga University/Dr. Soetomo Hospital	Surabaya		Indonesia
27	Ospedale Pediatrico Bambino Gesu	Rome		Italy	00165
28	Seoul National University Children's Hospital	Seoul		Korea, Republic of
29	Mother and Child Health Care	Belgrade		Serbia
30	University Children's Hospital	Belgrade		Serbia
31	University Children's Medical Institute, National University Hospital	Singapore		Singapore
32	King's College Hospital	London		United Kingdom	WC2R 2LS

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Investigators

Principal Investigator: Rajit K Basu, MD, Children's Hospital Medical Center, Cincinnati
Principal Investigator: Stuart Goldstein, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Rajit Basu, MD MS FAAP FCCM, Co-Director, Center for Acute Care Nephrology, Children's Hospital Medical Center, Cincinnati

ClinicalTrials.gov Identifier:

NCT01987921

Other Study ID Numbers:

Pediatric AWARE Study

First Posted:

Nov 20, 2013

Last Update Posted:

Sep 27, 2016

Last Verified:

Sep 1, 2016

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Rajit Basu, MD MS FAAP FCCM, Co-Director, Center for Acute Care Nephrology, Children's Hospital Medical Center, Cincinnati

Acute kidney injury

Pediatrics

Critical Care

Additional relevant MeSH terms:

Acute Kidney Injury

Study Results

No Results Posted as of Sep 27, 2016