Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates
NCT ID: NCT02443389
Last Updated: 2022-12-15
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
COMPLETED
Total Enrollment
2186 participants
Study Classification
OBSERVATIONAL
Study Start Date
2015-03-31
Study Completion Date
2016-03-31
Brief Summary
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Introduction:
Based on single-center data, approximately 1 of every 3 newborns admitted to tertiary level neonatal intensive care units (NICU) develops acute kidney injury (AKI), and those with AKI have significantly worse outcomes. To stimulate discussion among researchers, the NIH NIDDK sponsored a workshop on neonatal AKI in April 2013. At that workshop, the group recognized the need to improve collaborations between neonatologists and nephrologists within and across centers. The investigators have created a multi-institutional, multi-disciplinary group, Neonatal Kidney Collaborative (NKC), in order to address the following critical needs identified at the workshop: AWAKEN is the inaugural study of this new collaboration.
1. Development of a standardized evidence-based definition of neonatal AKI
2. Evaluation of risk factors that predispose neonatal to AKI
3. Investigation into how fluid provision/ balance impacts biochemical and clinical outcomes
Based on single-center data, approximately 1 of every 3 newborns admitted to tertiary level neonatal intensive care units (NICU) develops acute kidney injury (AKI), and those with AKI have significantly worse outcomes. To stimulate discussion among researchers, the NIH NIDDK sponsored a workshop on neonatal AKI in April 2013. At that workshop, the group recognized the need to improve collaborations between neonatologists and nephrologists within and across centers. The investigators have created a multi-institutional, multi-disciplinary group, Neonatal Kidney Collaborative (NKC), in order to address the following critical needs identified at the workshop: AWAKEN is the inaugural study of this new collaboration.
1. Development of a standardized evidence-based definition of neonatal AKI
2. Evaluation of risk factors that predispose neonatal to AKI
3. Investigation into how fluid provision/ balance impacts biochemical and clinical outcomes
Detailed Description
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The investigators will conduct a multi-center retrospective cohort 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 2013 at our centers who meet inclusion and exclusion criteria, and estimate that it can enroll approximately 3000 infants during this time.
A. Specific Aim 1: Determine if the proposed neonatal AKI definition adapted to neonates is able to predict mortality, length of stay, and discharge serum creatinine (SCr).
1. Our primary hypothesis is that higher stages of AKI are associated with mortality, even after controlling for severity of illness, interventions and demographics.
2. Populations
1. Inclusion Criteria - All infants born or admitted to a level 2 or 3 NICU will be screened. Infants who received intravenous fluids for \> 48 hours will be eligible.
2. Exclusion -- Infants admitted to the NICU at 2 weeks of age or older; Infants who undergo cardiovascular surgery repair of a congenital heart lesion within 1 week of life; Infants diagnosed with a lethal anomaly upon admission; Infants who die within 48 hours after birth
3. Primary Exposure - Neonatal AKI definitions (table 3)
4. Primary Outcome - Survival
1. In premature infants - defined as survival to 36 weeks post gestational age or hospital discharge (whichever comes first)
2. In term infants - defined as hospital survival to 28 days.
5. Secondary outcomes
1. Hospital length of stay
2. Last serum creatinine obtained
6. Potential confounders - gestational age, birth weight, 5 minute APGAR score, multiple gestation, significant renal anomalies, SNAP-II score
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 urine output, fluid balance and other factors.
B. Specific Aim 2: Define the risk factors associated with neonatal AKI.
1. Our hypothesis is that maternal and infant risk factors will predict AKI.
2. Population - same as in Specific Aim 1
3. Design - randomize cohort to a prediction and a validation groups. Develop a risk factor prediction model with the first group, and test the ability of the model to predict AKI with the second group.
4. Exposures (see full list in appendix 1 - Data collection sheets)
1. Maternal Demographic Factors
2. Neonatal Demographic Factors
3. Interventions / Medications
4. Co-Morbidities
5. Primary Outcome - KDIGO AKI definition modified for neonates (Table 3).
C. Specific Aim 3: Determine how fluid balance during the first few weeks of life relates to biochemical data and clinical outcomes.
1. Our hypotheses are that fluid provision affects chemistry panels (serum creatinine, blood urea nitrogen, serum sodium) and that fluid balance is associated with clinical outcomes.
2. Population - same as in Specific Aim 1
3. Design
1. Evaluation of fluid balance - will use birth weight as the reference weight and calculate changes in weight over time as a percentage of birth weight.
2. Will describe the association between fluid balance and changes in serum creatinine (SCr), blood urea nitrogen (BUN) and serum sodium.
3. Will then evaluate how fluid balance (and the associated biochemical changes) affects clinical outcomes.
4. Primary Clinical Outcome - Survival
1. In premature infants - defined as survival to 36 weeks post gestational age or hospital discharge (whichever comes first)
2. In term infants - defined as hospital survival to 28 days.
5. Secondary outcomes
1. Hospital length of stay
2. Ventilator free days in the first 28 days of life.
3. Bronchopulmonary dysplasia
4. Intraventricular hemorrhage
5. Last serum creatinine obtained
6. Use of blood pressure support medications
7. Use of diuretics
8. Patent ductus arteriosus
Data will be captured at each institution and entered into web-based forms in real time.
The investigators plan to have 5 different integrated forms:
1. Screening form
2. Baseline form for included infants
3. Daily Assessment form (first 7 days after birth)
4. Weekly Assessment form (weeks 2 - 18)
5. Discharge form
A. Specific Aim 1: Determine if the proposed neonatal AKI definition adapted to neonates is able to predict mortality, length of stay, and discharge serum creatinine (SCr).
1. Our primary hypothesis is that higher stages of AKI are associated with mortality, even after controlling for severity of illness, interventions and demographics.
2. Populations
1. Inclusion Criteria - All infants born or admitted to a level 2 or 3 NICU will be screened. Infants who received intravenous fluids for \> 48 hours will be eligible.
2. Exclusion -- Infants admitted to the NICU at 2 weeks of age or older; Infants who undergo cardiovascular surgery repair of a congenital heart lesion within 1 week of life; Infants diagnosed with a lethal anomaly upon admission; Infants who die within 48 hours after birth
3. Primary Exposure - Neonatal AKI definitions (table 3)
4. Primary Outcome - Survival
1. In premature infants - defined as survival to 36 weeks post gestational age or hospital discharge (whichever comes first)
2. In term infants - defined as hospital survival to 28 days.
5. Secondary outcomes
1. Hospital length of stay
2. Last serum creatinine obtained
6. Potential confounders - gestational age, birth weight, 5 minute APGAR score, multiple gestation, significant renal anomalies, SNAP-II score
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 urine output, fluid balance and other factors.
B. Specific Aim 2: Define the risk factors associated with neonatal AKI.
1. Our hypothesis is that maternal and infant risk factors will predict AKI.
2. Population - same as in Specific Aim 1
3. Design - randomize cohort to a prediction and a validation groups. Develop a risk factor prediction model with the first group, and test the ability of the model to predict AKI with the second group.
4. Exposures (see full list in appendix 1 - Data collection sheets)
1. Maternal Demographic Factors
2. Neonatal Demographic Factors
3. Interventions / Medications
4. Co-Morbidities
5. Primary Outcome - KDIGO AKI definition modified for neonates (Table 3).
C. Specific Aim 3: Determine how fluid balance during the first few weeks of life relates to biochemical data and clinical outcomes.
1. Our hypotheses are that fluid provision affects chemistry panels (serum creatinine, blood urea nitrogen, serum sodium) and that fluid balance is associated with clinical outcomes.
2. Population - same as in Specific Aim 1
3. Design
1. Evaluation of fluid balance - will use birth weight as the reference weight and calculate changes in weight over time as a percentage of birth weight.
2. Will describe the association between fluid balance and changes in serum creatinine (SCr), blood urea nitrogen (BUN) and serum sodium.
3. Will then evaluate how fluid balance (and the associated biochemical changes) affects clinical outcomes.
4. Primary Clinical Outcome - Survival
1. In premature infants - defined as survival to 36 weeks post gestational age or hospital discharge (whichever comes first)
2. In term infants - defined as hospital survival to 28 days.
5. Secondary outcomes
1. Hospital length of stay
2. Ventilator free days in the first 28 days of life.
3. Bronchopulmonary dysplasia
4. Intraventricular hemorrhage
5. Last serum creatinine obtained
6. Use of blood pressure support medications
7. Use of diuretics
8. Patent ductus arteriosus
Data will be captured at each institution and entered into web-based forms in real time.
The investigators plan to have 5 different integrated forms:
1. Screening form
2. Baseline form for included infants
3. Daily Assessment form (first 7 days after birth)
4. Weekly Assessment form (weeks 2 - 18)
5. Discharge form
Conditions
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Acute Kidney Injury
Keywords
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nephrotoxic
Fluid overload
Acute renal failure
Prematurity
Risk factors
Epidemiology
Study Design
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Observational Model Type
COHORT
Study Time Perspective
OTHER
Study Groups
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Neonates admitted to NICU
Retrospective cohort of neonates admitted to NICU with stated inclusion and exclusion criteria
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
1. All infants born or admitted to a level 2 or 3 NICU will be screened.
2. Infants who received intravenous fluids for \> 48 hours will be eligible.
2. Infants who received intravenous fluids for \> 48 hours will be eligible.
Exclusion Criteria
1. Infants admitted to the NICU at 2 weeks of age or older
2. Infants who undergo cardiovascular surgery repair of a congenital heart lesion within 1 week of life
3. Infants diagnosed with a lethal anomaly upon admission
4. Infants who die within 48 hours after birth
2. Infants who undergo cardiovascular surgery repair of a congenital heart lesion within 1 week of life
3. Infants diagnosed with a lethal anomaly upon admission
4. Infants who die within 48 hours after birth
Minimum Eligible Age
1 Minute
Maximum Eligible Age
2 Weeks
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Children's Hospital Medical Center, Cincinnati
OTHER
Sponsor Role
collaborator
George Washington University
OTHER
Sponsor Role
collaborator
McGill University
OTHER
Sponsor Role
collaborator
Albert Einstein College of Medicine
OTHER
Sponsor Role
collaborator
University of Rochester
OTHER
Sponsor Role
collaborator
University of British Columbia
OTHER
Sponsor Role
collaborator
University of Iowa
OTHER
Sponsor Role
collaborator
University of Michigan
OTHER
Sponsor Role
collaborator
University of New Mexico
OTHER
Sponsor Role
collaborator
University of Virginia
OTHER
Sponsor Role
collaborator
University of Washington
OTHER
Sponsor Role
collaborator
University of Miami
OTHER
Sponsor Role
collaborator
Case Western Reserve University
OTHER
Sponsor Role
collaborator
University of Kentucky
OTHER
Sponsor Role
collaborator
Maimonides Medical Center
OTHER
Sponsor Role
collaborator
Stony Brook University
OTHER
Sponsor Role
collaborator
The Canberra Hospital
OTHER
Sponsor Role
collaborator
Children's Hospital Colorado
OTHER
Sponsor Role
collaborator
St. Louis Children's Hospital
OTHER
Sponsor Role
collaborator
Baylor College of Medicine
OTHER
Sponsor Role
collaborator
Medanta, The Medicity, India
OTHER
Sponsor Role
collaborator
Ohio State University
OTHER
Sponsor Role
collaborator
University of Alabama at Birmingham
OTHER
Sponsor Role
lead
Responsible Party
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David Askenazi
MD, MsPH, Associate Professor
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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David Askenazi, MD
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Locations
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University of Alabama
Birmingham, Alabama, United States
Site Status
Countries
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United States
References
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Selewski DT, Gist KM, Nathan AT, Goldstein SL, Boohaker LJ, Akcan-Arikan A, Bonachea EM, Hanna M, Joseph C, Mahan JD, Mammen C, Nada A, Reidy K, Staples A, Wintermark P, Griffin R, Askenazi DJ, Guillet R; Neonatal Kidney Collaborative. The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group. Pediatr Res. 2020 Feb;87(3):550-557. doi: 10.1038/s41390-019-0579-1. Epub 2019 Sep 19.
Reference Type
BACKGROUND
Starr MC, Boohaker L, Eldredge LC, Menon S, Griffin R, Mayock D, Askenazi D, Hingorani S; Neonatal Kidney Collaborative. Acute Kidney Injury is Associated with Poor Lung Outcomes in Infants Born >/=32 Weeks of Gestational Age. Am J Perinatol. 2020 Jan;37(2):231-240. doi: 10.1055/s-0039-1698836. Epub 2019 Nov 18.
Reference Type
BACKGROUND
Askenazi D, Abitbol C, Boohaker L, Griffin R, Raina R, Dower J, Davis TK, Ray PE, Perazzo S, DeFreitas M, Milner L, Ambalavanan N, Cole FS, Rademacher E, Zappitelli M, Mhanna M; Neonatal Kidney Collaborative. Optimizing the AKI definition during first postnatal week using Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) cohort. Pediatr Res. 2019 Feb;85(3):329-338. doi: 10.1038/s41390-018-0249-8. Epub 2018 Dec 13.
Reference Type
BACKGROUND
Charlton JR, Boohaker L, Askenazi D, Brophy PD, D'Angio C, Fuloria M, Gien J, Griffin R, Hingorani S, Ingraham S, Mian A, Ohls RK, Rastogi S, Rhee CJ, Revenis M, Sarkar S, Smith A, Starr M, Kent AL; Neonatal Kidney Collaborative. Incidence and Risk Factors of Early Onset Neonatal AKI. Clin J Am Soc Nephrol. 2019 Feb 7;14(2):184-195. doi: 10.2215/CJN.03670318. Epub 2019 Jan 31.
Reference Type
BACKGROUND
Harer MW, Askenazi DJ, Boohaker LJ, Carmody JB, Griffin RL, Guillet R, Selewski DT, Swanson JR, Charlton JR; Neonatal Kidney Collaborative (NKC). Association Between Early Caffeine Citrate Administration and Risk of Acute Kidney Injury in Preterm Neonates: Results From the AWAKEN Study. JAMA Pediatr. 2018 Jun 4;172(6):e180322. doi: 10.1001/jamapediatrics.2018.0322. Epub 2018 Jun 4.
Reference Type
BACKGROUND
Kraut EJ, Boohaker LJ, Askenazi DJ, Fletcher J, Kent AL; Neonatal Kidney Collaborative (NKC). Incidence of neonatal hypertension from a large multicenter study [Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates-AWAKEN]. Pediatr Res. 2018 Aug;84(2):279-289. doi: 10.1038/s41390-018-0018-8. Epub 2018 May 23.
Reference Type
BACKGROUND
Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Rohatgi S, Soranno DE, Chishti AS, Woroniecki R, Mammen C, Swanson JR, Sridhar S, Wong CS, Kupferman JC, Griffin RL, Askenazi DJ; Neonatal Kidney Collaborative (NKC). Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017 Nov;1(3):184-194. doi: 10.1016/S2352-4642(17)30069-X.
Reference Type
BACKGROUND
Selewski DT, Akcan-Arikan A, Bonachea EM, Gist KM, Goldstein SL, Hanna M, Joseph C, Mahan JD, Nada A, Nathan AT, Reidy K, Staples A, Wintermark P, Boohaker LJ, Griffin R, Askenazi DJ, Guillet R; Neonatal Kidney Collaborative. The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group. Pediatr Res. 2019 Jan;85(1):79-85. doi: 10.1038/s41390-018-0183-9. Epub 2018 Sep 20.
Reference Type
BACKGROUND
Kirkley MJ, Boohaker L, Griffin R, Soranno DE, Gien J, Askenazi D, Gist KM; Neonatal Kidney Collaborative (NKC). Acute kidney injury in neonatal encephalopathy: an evaluation of the AWAKEN database. Pediatr Nephrol. 2019 Jan;34(1):169-176. doi: 10.1007/s00467-018-4068-2. Epub 2018 Aug 28.
Reference Type
BACKGROUND
Charlton JR, Boohaker L, Askenazi D, Brophy PD, Fuloria M, Gien J, Griffin R, Hingorani S, Ingraham S, Mian A, Ohls RK, Rastogi S, Rhee CJ, Revenis M, Sarkar S, Starr M, Kent AL; Neonatal Kidney Collaborative (NKC). Late onset neonatal acute kidney injury: results from the AWAKEN Study. Pediatr Res. 2019 Feb;85(3):339-348. doi: 10.1038/s41390-018-0255-x. Epub 2018 Dec 13.
Reference Type
BACKGROUND
Jetton JG, Guillet R, Askenazi DJ, Dill L, Jacobs J, Kent AL, Selewski DT, Abitbol CL, Kaskel FJ, Mhanna MJ, Ambalavanan N, Charlton JR; Neonatal Kidney Collaborative. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study. Front Pediatr. 2016 Jul 19;4:68. doi: 10.3389/fped.2016.00068. eCollection 2016.
Reference Type
BACKGROUND
Kent AL, Charlton JR, Guillet R, Gist KM, Hanna M, El Samra A, Fletcher J, Selewski DT, Mammen C. Neonatal Acute Kidney Injury: A Survey of Neonatologists' and Nephrologists' Perceptions and Practice Management. Am J Perinatol. 2018 Jan;35(1):1-9. doi: 10.1055/s-0037-1604260. Epub 2017 Jul 14.
Reference Type
BACKGROUND
Stoops C, Boohaker L, Sims B, Griffin R, Selewski DT, Askenazi D; on behalf of the National Kidney Collaborative (NKC). The Association of Intraventricular Hemorrhage and Acute Kidney Injury in Premature Infants from the Assessment of the Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study. Neonatology. 2019;116(4):321-330. doi: 10.1159/000501708. Epub 2019 Aug 28.
Reference Type
BACKGROUND
Other Identifiers
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X140917002
Identifier Type: -
Identifier Source: org_study_id