CClinicalTrials.gg
Enrolling by invitationNCT06823115AWAKEN 2Updated Sep 4, 2026

Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates 2.0

An observational study in Acute Kidney Injury, Fluid Overload and Prematurity Complications, sponsored by Indiana University. Enrolling by invitation at 87 sites in 19 countries. Open to participants aged 0 Minutes to 2 Weeks. Per ClinicalTrials.gov, last updated 2026-09-04.

Sponsored by Indiana University · Observational

Study type
Observational
Model
Cohort
Time perspective
Retrospective
Enrollment
4,000
Ages
0 Minutes to 2 Weeks
Sex
All
01

Study summary

There is a growing focus on short- and long-term kidney health in neonates, including those with acute kidney injury (AKI). AKI occurs commonly in the Neonatal Intensive Care Unit (NICU) and is associated with adverse outcomes. In addition to poor outcomes during the hospitalization, infants discharged from the NICU may have an increased burden of kidney disease during childhood. Studies of long-term kidney function in children born prematurely show a fourfold increase in chronic kidney disease (CKD) by adolescence and into adulthood.

Despite the landmark findings of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, the limitations of this study are notable. First, the AWAKEN study enrolled infants admitted in 2014, making the data now over 10 years old. Much has changed in neonatal practice (e.g. increased AKI awareness, treatment strategies). Secondly, the findings of the AWAKEN study were geographically limited. While the AWAKEN study was multi-national and multi-center, it represented only 24 centers (22 from North America, 1 from India and 1 from Australia). Finally, information collected from AWAKEN ended at hospital discharge.

The investigators seek to leverage the strength of the Neonatal Kidney Collaborative along with other organizations and collaboratives interested in neonatal kidney health to address these gaps. Therefore, the investigators are conducting a second, modified iteration of this study entitled "AWAKEN 2.0". AWAKEN 2.0 will be a multi-center multi-national retrospective analysis utilizing similar methodology to the AWAKEN study.

Read the detailed description

AWAKEN 2.0 is a multi-center multi-national retrospective analysis utilizing similar methodology to the AWAKEN study. The investigators will capture information on all infants admitted to participating level 3 and 4 NICUs between January 1-March 31, 2019, to answer specific hypothesis regarding the following three inter-connected but independent specific aims:

Specific Aim 1. Describe prevalence of AKI in a multi-national multi-center retrospective cohort, 5 years after the original AWAKEN study.

  1. Primary hypothesis: The investigators hypothesize that rates of neonatal AKI are higher than the rate described in the original AWAKEN study.
  2. Population:

    1. Inclusion Criteria include all infants admitted to participating NICUs between 1/1/19- 3/31/19 and receiving > 48 hours of IV fluids
    2. Exclusion Criteria include age > 14 days at admission, congenital heart disease requiring transfer for escalation of CHD care and/or surgery within the first 7 days, lethal chromosomal anomalies and/or neonatal mortality \<48 hours
  3. Primary Outcome - Neonatal AKI
  4. Potential confounders - gestational age, birth weight, 5 minute APGAR score, multiple gestation, significant renal anomalies, site characteristics.

Specific Aim 2. Determine if AKI is independently associated with mortality, length of stay, and discharge serum creatinine (SCr).

  1. The investigators hypothesize that higher stages of AKI are associated with higher mortality, longer lengths of stay and higher serum creatinine at discharge, even after controlling for confounding factors.
  2. Populations - Same as Specific Aim 1.
  3. Primary Exposure - Neonatal AKI definitions (table 3)
  4. Primary Outcome - Survival
  5. Secondary outcomes will include: Hospital length of stay, BPD.
  6. Potential confounders - gestational age, birth weight, 5 minute APGAR score, multiple gestation, significant renal anomalies,
  7. Exploratory outcomes - recognize that the proposed definition may not be the best definition to predict clinical outcomes. Also recognize that there may be a need to have different definitions for premature infants. The investigators plan to explore how other definitions reported in the literature can predict these outcomes (for example using the 90th % for normative values). In addition, this will have the largest comprehensive database to explore new definitions which could incorporate fluid balance and other factors.

Specific Aim 3. Determine if AKI can predict chronic kidney disease, recurrent AKI and hypertension during early childhood.

  1. The investigators hypothesize that higher stages of AKI are associated with chronic kidney disease and recurrent AKI during early childhood.
  2. Population - Same as Specific Aim 1
  3. Primary Exposure - Neonatal AKI definitions (table 3)
  4. Primary Outcome - Childhood CKD
  5. Secondary Outcomes - Childhood hypertension, recurrent AKI and childhood ESRD.

Each participating site will screen all neonates admitted to the NICU during the 3 months of study and capture additional data on those who meet the same inclusion and exclusion criteria as the original cohort. There will be 6 different integrated forms.

  1. Screening form (all infants)
  2. Baseline form for included infants (maternal demographic data, admission indication)
  3. First 14 days form (i.e. urine output, medications and respiratory support)
  4. Serum creatinine data (all values from date of birth to date of IRB approval)
  5. Discharge form (discharge diagnoses, medications, follow-up anticipated)
  6. Follow-up Information (clinically obtained follow-up after discharge)
02

Conditions studied

  • Acute Kidney Injury
  • Fluid Overload
  • Prematurity Complications
  • Risk Factors
  • Epidemiology
  • Chronic Kidney Disease(CKD)
  • Hypertension

Keywords

  • acute kidney injury
  • chronic kidney disease
  • neonates
  • prematurity
  • hypertension
03

Who can participate

Ages eligible
0 Minutes to 2 Weeks
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

The investigators will conduct a multi-center retrospective cohort study. All infants admitted to the NICU between January 1, 2019 and March 31, 2019 will be screened for the study.The investigators will enroll eligible infants who meet inclusion and exclusion criteria at each center for 3 consecutive months. Based on average admissions for 2018 at our centers who meet inclusion and exclusion criteria, it is estimated that it can enroll approximately 4000 infants during this time.

Inclusion criteria

  1. All infants born or admitted to a participating level 3 or 4 NICU between 1/1/19- 3/31/19 will be screened.
  2. Infants who received intravenous fluids for > 48 hours will be eligible.

Exclusion criteria

Exclusion Criteria:

  1. Age > 14 days at admission
  2. Congenital heart disease requiring transfer for escalation of CHD care and/or surgery within the first 7 days
  3. Lethal chromosomal anomalies
  4. Neonatal mortality \<48 hours
04

Study design

Observational model
Cohort
Time perspective
Retrospective
Enrollment
4,000 participants (estimated)
Patient registry
No

Groups and cohorts

  • Neonates at Risk of Kidney Disease

    Inclusion Criteria 1. Admitted to participating NICUs between 1/1/19- 3/31/19 2. \> 48 hours of IV fluids Exclusion Criteria 1. Age \> 14 days at admission 2. Congenital heart disease requiring transfer for escalation of CHD care and/or surgery within the first 7 days 3. Lethal chromosomal anomalies 4. Neonatal mortality \<48 hours

05

What researchers measure

Primary outcomes

  1. Neonatal Acute Kidney Injury

    The investigators will evaluate the rate of neonatal AKI among infants that meet inclusion criteria across all sites. Neonatal Acute Kidney Injury will be defined by the standard neonatal definitions, including serum creatinine values and urine output (when available). Furthermore, investigators will examine if different thresholds or definitions of AKI will better predict outcomes.

    Time frame: Up to 6 months or NICU discharge, whichever comes first

Secondary outcomes

  1. Risk factors for Neonatal AKI

    Define the major risk factors associated with neonatal AKI. The investigators will randomly split the cohort into two groups. The investigators will develop a risk factor prediction model with the first group, and test the ability of the model to predict AKI with the second group.

    Time frame: Up to 6 months or NICU discharge, whichever comes first

  2. Fluid Overload

    Fluid overload will be calculated based on daily weights and intake and output values. We will determine how fluid balance during the first few weeks of life relates to biochemical data and clinical outcomes.

    Time frame: NICU admission through discharge.

  3. Mortality

    Determine if the KDIGO AKI definition adapted to neonates can predict mortality. Investigators will also evaluate if other thresholds or proposed AKI definitions can better predict mortality.

    Time frame: Up to 6 months or NICU discharge, whichever comes first

  4. Chronic Kidney Disease

    In infants with available follow-up data clinically obtained, investigators will determine the rates of both clinically diagnosed (by ICD code or note) and laboratory determined Chronic Kidney Disease (using the CKID-U25 eGFR definitions).

    Time frame: NICU discharge to 5 year follow-up

  5. Hypertension

    In infants with available follow-up data clinically obtained, investigators will determine the rates of both clinically diagnosed (by ICD code or note) and value determined hypertension (using AAP Hypertension thresholds)

    Time frame: NICU discharge to 5 year follow-up

  6. Proteinuria

    In infants with available follow-up data clinically obtained, investigators will determine the rates of both clinically diagnosed (by ICD code or note) and laboratory determined proteinuria.

    Time frame: NICU discharge to 5 year follow-up

06

Study locations

87 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas 72202, United States
  • Stanford Children's
    Palo Alto, California 94304, United States
  • Rady Children's Hospital/UCSD
    San Diego, California 92123, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • Yale University
    New Haven, Connecticut 06511, United States
  • Children's National Hospital
    Washington D.C., District of Columbia 20010, United States
  • Miami Children's / Nichlaus Children's Hospital
    Miami, Florida 33155, United States
  • Baptist Health South Florida/South Miami Hospital
    South Miami, Florida 33176, United States
  • Emory Healthcare / Children's Healthcare of Atlanta
    Atlanta, Georgia 30322, United States
  • Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
  • SIU
    Springfield, Illinois 62702, United States
  • Indiana University School of Medicine
    Indianapolis, Indiana 46202, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • University of Iowa
    Iowa City, Iowa 52242, United States
  • University of Kentucky
    Lexington, Kentucky 40536, United States
  • University of Louisville
    Louisville, Kentucky 40202, United States
  • University of Maryland
    Baltimore, Maryland 21201, United States
  • Johns Hopkins University/Hospital
    Baltimore, Maryland 21287, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Children's Mercy Hospital
    Kansas City, Missouri 64108, United States
  • Washington University
    St Louis, Missouri 63110, United States
  • Children's Nebraska
    Omaha, Nebraska 68114, United States
  • Maimonides Medical Center
    Brooklyn, New York 11219, United States
  • Cohen Children's Hospital
    Queens, New York 11040, United States
  • University of Rochester / Golisano Children's Hospital
    Rochester, New York 14642, United States
  • Stony Brook Medicine
    Stony Brook, New York 11794, United States
  • Children's Hospital at Montefiore
    The Bronx, New York 10467, United States
  • Westchester Medical Center/Maria Fareri Children's Hospital
    Westchester, New York 10595, United States
  • UNC
    Chapel Hill, North Carolina 27514, United States
  • Wake Forest
    Winston-Salem, North Carolina 27157, United States
  • Akron Children's Hospital
    Akron, Ohio 44308, United States
  • Cincinnati Children's Hospital
    Cincinnati, Ohio 45229, United States
  • Nationwide Children's
    Columbus, Ohio 43205, United States
  • OHSU
    Portland, Oregon 97239, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Monroe Carell Jr. Children's Hospital at Vanderbilt
    Nashville, Tennessee 37232, United States
  • UT Southwestern
    Dallas, Texas 75235, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • Texas Tech
    Lubbock, Texas 79415, United States
  • Christus Children's Hospital
    San Antonio, Texas 78207, United States
  • Primary Children's Hospital
    Salt Lake City, Utah 84113, United States
  • Golisano Children's Hospital at University of Vermont Health
    Burlington, Vermont 05401, United States
  • University of Virginia
    Charlottesville, Virginia 22930, United States
  • Seattle Children's Hospital / University of Washington
    Seattle, Washington 98105, United States
  • University of Wisconsin
    Madison, Wisconsin 53792, United States
  • Medical College of Wisconsin / Children's Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • The Royal Children's Hospital Melbourne
    Melbourne, Victoria, Australia
  • Perth Children's Hospital
    Perth, Australia
  • Joana de Gusmao Children's Hospital
    Florianópolis, Brazil
  • Hospital de Clinicas de Porto Alegre
    Porto Alegre, Brazil
  • The Hospital for Sick Children
    Toronto, Ontario, Canada
  • Alberta Children's Hospital/University of Calgary
    Calgary, Canada
  • Stollery Children's Hospital
    Edmonton, Canada
  • McMaster Children's Hospital
    Hamilton, Canada
  • McGill University
    Montreal, Canada
  • Mount Sinai Hospital
    Toronto, Canada
  • Sunnybrook Health Sciences Center
    Toronto, Canada
  • Hospital Occidente de Kennedy
    Bogotá, Colombia
  • Fundacion Valle del Lili Cali
    Cali, Colombia
  • Clínica Universitaria Bolivariana
    Medellín, Colombia
  • Institute for the Care of Mother and Child
    Prague, Czechia
  • University of Cologne
    Cologne, Germany
  • Aghia Sofia Children's Hospital
    Athens, Greece
  • University Hospital of Heraklion
    Heraklion, Greece
  • Aristotle University
    Thessaloniki, Greece
  • Hippokration General Hospital of Thessaloniki
    Thessaloniki, Greece
  • University of Szeged Children's Hospital
    Szeged, Hungary
  • St. John's Medical College Hospital
    Bengaluru, India
  • Dr. Mehta's Hospitals
    Chennai, India
  • Christian Medical College
    Vellore, India
  • Centro de Alta Especialidad del Estado de Veracruz
    Veracruz, Mexico
  • Amalia Children's Hospital Radboudumc
    Nijmegen, Netherlands
  • University of Ibadan
    Ibadan, Nigeria
  • Hospital Santa Maria, Unidade Local de Saude de Santa Maria
    Lisbon, Portugal
  • Centro Materno Infantil de Norte Albino Aroso, Unidade Local de Saude de Santo Antonio
    Porto, Portugal
  • ULS Sao Joan
    Porto, Portugal
  • University Medical Centre Ljubljana
    Ljubljana, Slovenia
  • Puerta del Mar University Hospital
    Cadiz, Spain
  • Cukurova University
    Adana, Turkey (Türkiye)
  • Ankara Bilkent City Hospital, Children Hospital
    Ankara, Turkey (Türkiye)
  • Marmara University Pendik Research and Training Hospital
    Istanbul, Turkey (Türkiye)
  • St Francis Nsambya
    Kampala, Uganda
  • Bukovinian State Medical University
    Chernivtsi, Ukraine
07

References and documents

Individual participant data

Plan to share: No — As a retrospective study and based on terms of the data sharing agreements between sites, individual patient level data will not be made available. Investigators that have questions that may be answered by the data will be able to present proposal to request secondary data analyses to be conducted on de-identified data.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06823115
Lead sponsor
Indiana University
Collaborators
Neonatal Kidney Collaborative
Responsible party
Michelle Casey Starr (Associate Professor of Pediatrics, Indiana University) — Principal investigator
First posted
Feb 12, 2025
Start date
Mar 1, 2025
Primary completion
Jan 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Sep 4, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

No contact was published for this record. The registry link below has the sponsor’s details.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion