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

Acute Kidney Injury Clinical Trial

— AWARE  

Official title:

Assessment of Worldwide AKI in Pediatrics, Renal Angina and Epidemiology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01987921
• Other study ID #: Pediatric AWARE Study
• Status: Completed
• Phase: N/A
• First received: November 13, 2013
• Last updated: September 25, 2016
• Start date: January 2014
• Est. completion date: December 2014

Study information

• Verified date: September 2016
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Description:

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

1. 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.

2. Validate the precision of RAI in ruling out AKI in a large, heterogeneous study population.

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5237
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 25 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Locations

Country	Name	City	State
Australia	The Sydney Children's Hospitals Network	Sydney
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Canada	University of Edmonton	Edmonton
Canada	Montreal Children's/McGill	Montreal
Canada	University of British Columbia and Children's and Women's Health Center of British Columbia Branch	Vancouver
China	Nanjing Children's Hospital	Nanjing
Indonesia	Dept of Child Health Cipto Mangunkusumo/University of Indonesia	Jakarta
Indonesia	Dept of Child Health Airlangga University/Dr. Soetomo Hospital	Surabaya
Italy	Ospedale Pediatrico Bambino Gesu	Rome
Korea, Republic of	Seoul National University Children's Hospital	Seoul
Serbia	Mother and Child Health Care	Belgrade
Serbia	University Children's Hospital	Belgrade
Singapore	University Children's Medical Institute, National University Hospital	Singapore
United Kingdom	King's College Hospital	London
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Alabama	Birmingham	Alabama
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Iowa	Des Moines	Iowa
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Yale University	New Haven	Connecticut
United States	Cohen Children's Medical Center of NY	New Hyde Park	New York
United States	Stanford University	Palo Alto	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University in St. Louis	St. Louis	Missouri
United States	Stony Brook Long Island Children's Hospital	Stony Brook	New York
United States	Nemours/Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Indonesia,  Italy,  Korea, Republic of,  Serbia,  Singapore,  United Kingdom, 

References & Publications (2)

Basu RK, Kaddourah A, Terrell T, Mottes T, Arnold P, Jacobs J, Andringa J, Armor M, Hayden L, Goldstein SL. Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): A Prospective Study to Improve Diagn — View Citation

Basu RK, Kaddourah A, Terrell T, Mottes T, Arnold P, Jacobs J, Andringa J, Goldstein SL; Prospective Pediatric AKI Research Group (ppAKI). Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in critically ill children (AWARE): study — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Increase in pre-test probability of AKI risk using the renal angina index	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.	3-4 days	No
Other	Biomarker incorporation into renal angina index	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	3-4 days	No
Primary	Severe AKI in first seven 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	Within 7 Days of ICU admission	No
Secondary	AKI Conferred Risk on Mortality	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).	28 days	No
Secondary	Comparison of AKI by Creatinine and Urine Output	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.	7 and 28 days	No
Secondary	Determination of AKI Progression	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.	7 days	No
Secondary	Identification of Predictors of Severe AKI	Variables with independent associations for increased risk of severe AKI in the first seven days will be identified.	7 days	No

External Links

•   Website dedicated to pediatric AKI and has specific information about AWARE