Acute Kidney InjuryNeoAKISTOPNCT05851222
A Big Data Approach to Predict NEOnatal Acute Kidney Injury in Newborns expoSed to nephroTOxic Drugs (NeoAKI STOP)
An observational study of Acute Kidney Injury and Drug Use, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial summary
This observational retrospective study aims to learn about the incidence of acute kidney (AKI) injury in newborns in infants exposed to nephrotoxic drugs with a big data approach. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Kidney Injury, Drug Use, Drug Interaction
- How many people
- 4,200 participants
- Where
- 1 siteItaly
- Study dates
- 1 Aug 2023to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: patients admitted to NICU and born between January 2010 and December 2022
Who may be able to join
- born between 01/01/2010 and 31/12/2022;
- admitted within 24 hours of birth in the NICU (both inborn and outborn);
- availability of at least two serum creatinine values or a daily hourly diuresis assessment in the first 30 days of life.
Who cannot join
- pre- or postnatal diagnosis of severe urologic and/or nephrologic pathology on a malformative and/or genetic basis;
- finding of serum creatinine > 2 mg/dl in the first 24 hours of life;
- genetic conditions that may impact patient survival or renal function;
- length of stay in the NICU less than 48 hours (death or transfer to another department);
- infants undergoing ECMO.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milan, MI, 20129
About this study
Official title: Predicting Acute Kidney Injury in Infants Exposed to Nephrotoxic Drugs: A Big Data Approach to Predict NEOnatal Acute Kidney Injury in Newborns expoSed to nephroTOxic Drugs. (NeoAKI STOP)
This observational retrospective study aims to learn about the incidence of acute kidney (AKI) injury in newborns in infants exposed to nephrotoxic drugs with a big data approach.
The main question it aims to answer are:
- Develop a model that can predict the occurrence of AKI in infants admitted to the NICU;
- Identify the drug or combination of drugs associated with an increased risk of AKI.
The group of infants exposed to drugs will be defined based on exposure for at least 1-day tone one or more therapies commonly used in the NICU. Once the AKI event has occurred, the observation of the trend of daily creatinine and diuresis values will be continued for the period covered by the study.
Read the detailed description
- Rationale and background Acute Kidney Injury (AKI) is defined as the sudden impairment of kidney function that results in altered hydro electrolyte balance and renal waste product elimination. Extensive evidence shows that the onset of AKI in critically ill pediatric patients is associated with an increased risk of death and a longer length of hospitalization. Furthermore, in patients who survive an episode of AKI, there is an increased risk of developing long-term morbidity, particularly Chronic Kidney Disease (CKD). The neonatal kidney has numerous features on the pathophysiological level that predispose this population more to AKI than at other life ages. In addition to the peculiarities related to the development and physiology of the kidney, especially if preterm, infants admitted to the NICU are exposed to multiple risk factors that may contribute to the onset of AKI. A recent multicenter study conducted in neonatal intensive care units in Canada, Australia, India, and the United States reported an overall incidence of AKI of 29.9% and showed that the development of AKI is an independent risk factor for death and prolonged hospitalization. The incidence of AKI by gestational age also showed a typical U-shaped distribution, with the greater occurrence at the two extremes represented by infants with gestational ages >36 weeks (36.7%) and <29 weeks (47.9%), while the lowest value was recorded in the 29-36 weeks range. The risk of developing acute kidney injury is known to increase with the number of medications used (especially if > 3) and the duration of exposure, especially for the aminoglycoside antibiotic category. In addition, critically ill patients who developed AKI were generally more exposed to nephrotoxic drugs than those who did not develop AKI. In the NICU setting, it is estimated that 87% of VLBW infants are exposed to at least one nephrotoxic drug during their hospital stay, and about a quarter of these infants develop at least one episode of acute renal distress. The diagnosis of AKI is based on increased serum creatinine (SCr) or decreased urinary output. To date, the definition of acute kidney injury is based on the former Kidney Disease Improving Global Outcomes (KIDGO) criteria modified for newborns. However, in light of the premises made, it can be understood how creatinine monitoring allows only passive observation of the phenomenon, noting the rise in creatinine values when renal insult has already occurred by then. This allows only retrospective changes in some aspects of the infant's management, such as optimizing fluid intake, suspending the administration of nephrotoxic drugs, and correcting any electrolyte imbalances, but without being able to prevent the onset of AKI. Ideally, the investigators should be able to understand and predict how different risk factors contribute to the beginning of renal damage in a given patient, thus allowing individualized management. Given the complexity of patients admitted to the NICU and the number of variables in the field, the problem lends itself well to analysis through AI and general statistical inference methods. Such methods have previously been used successfully for studies on adult patients but, to our knowledge, never on newborn patients. The investigators hope to apply these models in a prospective cohort study to validate their use and develop a real-time monitoring system of the kidney well-being of our nephrotoxic drug-exposed infants that can guide the clinician in patient management. Indeed, systematic surveillance of at-risk patients can significantly reduce the onset of kidney damage and limit both short-term and long-term consequences, thereby improving neonatal outcomes.
- Research question and objectives 2.1 Primary objectives
- Develop a model that can predict the occurrence of AKI in infants admitted to the NICU;
- Identify the drug or combination associated with an increased risk of AKI. 2.2 Secondary objectives
- Identify subgroups of patients at increased risk of AKI;
- Identify time windows at increased risk of AKI during NICU admission.
- Methods 3.1 Study design Single-center retrospective observational cohort study at the UOC of Neonatology and Neonatal Intensive Care Unit of Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 3.1.1 Primary endpoints
- Development of AKI defined according to modified KIDGO criteria for the newborn based on increased serum creatinine values or reduced mean hourly diuresis during NICU admission. 3.1.2 Secondary endpoints
- Number of AKI cases in risk subcategories: very low birth weight (birth weight < 1500 g), extremely low birth weight (birth weight < 1000 g), cardiopathic, with surgical pathology, sepsis, asphyxia;
- Number of AKI cases in the first week of hospitalization compared with other periods.
- Setting A population of infants admitted to the NICU of the Foundation will be retrospectively considered. 4.1 Study population The study population will consist of patients born between January 2010 and December 2022.
- Inclusion criteria
- Patients who meet all of the following criteria will be included in the study:
- born between 01/01/2010 and 31/12/2022;
- admitted within 24 hours of birth in the NICU (both inborn and outborn);
- availability of at least two serum creatinine values or a daily hourly diuresis assessment in the first 30 days of life.
- Exclusion Criteria Patients who meet even one of the following criteria will be excluded:
- pre- or postnatal diagnosis of severe urologic and/or nephrologic pathology on a malformative and/or genetic basis;
- finding of serum creatinine > 2 mg/dl in the first 24 hours of life;
- genetic conditions that may impact patient survival or renal function;
- length of stay in the NICU less than 48 hours (death or transfer to another department);
- infants undergoing ECMO.
- Variables Clinical and instrumental data regarding each patient's medical history will be acquired for the NICU admission by the first month of life. Definition of AKI All available serum creatinine values for each patient during the NICU admission will be recorded, considering that determinations made within the first 48 hours of the infant's life are affected by maternal creatinine values. The presence of AKI will be determined according to the modified KIDGO criteria for the newborn, as reported in previous work in the neonatal setting. Exposure to drugs. The group of infants exposed to drugs will be defined based on exposure for at least 1-day tone one or more therapies commonly used in the NICU. Special attention will be given to exposure to antibiotics, antivirals, antifungals, diuretics, anti-inflammatories, inotropes, and vasopressors. In addition to the active ingredient, other significant data such as prescribed dose, administration route, treatment duration, and temporal relationship between treatment and diagnosis of AKI will also be considered. Once the AKI event has occurred, the observation of the trend of daily creatinine and diuresis values will be continued for the period covered by the study.
- Source documents Data will be collected from each newborn's Neocare electronic medical record (GPI SpA).
- Sample size Approximately 600 newborns are admitted to the neonatal intensive care unit each year. The incidence of renal damage in the critically ill newborn population is reported in the literature to be approximately 30%. In light of these considerations, over the decade of our observation, the estimated number of infants admitted to the NICU is about 6000 patients. Assuming a 30% drop-out related to exclusion criteria (about 1800 subjects), the investigators expect to be able to include approximately 4200 subjects in the study, among whom the investigators should find about 1200 cases of acute renal damage.
- Data management Data will be collected anonymously by assigning a code to each patient. They will then be organized and stored on data storage systems with secure access.
- Data Analysis Data will be analyzed using statistical inference approaches peculiar to Data Science and Artificial Intelligence (AI), such as Decision Trees, Logistic Regression, and Machine Learning (ML). The data themselves will suggest the choice of methods used.
- Primary endpoint: analysis Identifying patterns or items in the administration of so-called off-label drugs in the neonatal patient (premature or not) and the development of renal syndromes related to the administration of the drug itself. Once one or more correlation factors have been identified, they could be entered within the Electronic Medical Record system (and in particular within the Clinical Decision Support System) in order to be able to alert the treating clinical staff of any clinical risk associated with the administration.
- Secondary endpoint: analysis Development of a computational Early Warning model for AKI that ensures the interpretability of the prediction.
- Conditions
- Acute Kidney Injury, Drug Use, Drug Interaction, Drug Toxicity, Drug-Induced Nephropathy, Machine Learning
- Medical subject headings
- Acute Kidney Injury, Drug-Related Side Effects and Adverse Reactions, Premature Birth
What is being measured
The primary outcome is the main question the study is designed to answer.
Develop a model that can predict the occurrence of AKI in infants admitted to the NICU;
All available serum creatinine values for each patient during the NICU admission will be recorded, considering that determinations made within the first 48 hours of the infant's life are affected by maternal creatinine values.
The presence of AKI will be determined according to the modified KIDGO criteria for the newborn, as reported in previous work in the neonatal setting (Jetton JG, 2017; Jetton JG and Askenazi DJ, 2012; Stoops C, 2016; Askenazi DJ, Patil NR, et al., 2015; Sarkar S, 2014).
Measured: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
Identify the drug or combination of drugs associated with an increased risk of AKI
The group of infants exposed to drugs will be defined based on exposure for at least 1-day tone one or more therapies commonly used in the NICU. Special attention will be given to exposure to antibiotics, antivirals, antifungals, diuretics, anti-inflammatories, inotropes, and vasopressors. In addition to the active ingredient, other significant data such as prescribed dose, administration route, treatment duration, and temporal relationship between treatment and diagnosis of AKI will also be considered.
Measured: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
Secondary outcomes (2)
Identify subgroups of patients at increased risk of AKI
Number of AKI cases in risk subcategories: very low birth weight (birth weight < 1500 g), extremely low birth weight (birth weight < 1000 g), cardiopathic, with surgical pathology, sepsis, asphyxia
Measured: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
Identify time windows at increased risk of AKI during NICU admission.
Number of AKI cases in the first week of hospitalization compared with other periods
Measured: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start1 Aug 2023 (estimated)
- Primary completion30 Sep 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (44)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 4,200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giacomo Cavallaro, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Investigators
- Giacomo Cavallaro, MD, PhD, Study director, Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoIlaria Amodeo, MD, Principal investigator, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05851222
- Sponsor's protocol ID
- NeoAKI STOP
- Acronym
- NeoAKISTOP
- Status last verified
- May 2023
- First submitted
- 9 Apr 2023
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abitbol CL, Seeherunvong W, Galarza MG, Katsoufis C, Francoeur D, Defreitas M, Edwards-Richards A, Master Sankar Raj V, Chandar J, Duara S, Yasin S, Zilleruelo G. Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate? J Pediatr. 2014 May;164(5):1026-1031.e2. doi: 10.1016/j.jpeds.2014.01.044. Epub 2014 Mar 5.
PubMed 24607244Askenazi D, Patil NR, Ambalavanan N, Balena-Borneman J, Lozano DJ, Ramani M, Collins M, Griffin RL. Acute kidney injury is associated with bronchopulmonary dysplasia/mortality in premature infants. Pediatr Nephrol. 2015 Sep;30(9):1511-8. doi: 10.1007/s00467-015-3087-5. Epub 2015 Mar 26.
PubMed 25808019Askenazi DJ, Feig DI, Graham NM, Hui-Stickle S, Goldstein SL. 3-5 year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int. 2006 Jan;69(1):184-9. doi: 10.1038/sj.ki.5000032.
PubMed 16374442Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, Ambalavanan N. Urine biomarkers predict acute kidney injury in newborns. J Pediatr. 2012 Aug;161(2):270-5.e1. doi: 10.1016/j.jpeds.2012.02.007. Epub 2012 Mar 16.
PubMed 22424940Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Patil N, Ambalavanan N. Fluid overload and mortality are associated with acute kidney injury in sick near-term/term neonate. Pediatr Nephrol. 2013 Apr;28(4):661-6. doi: 10.1007/s00467-012-2369-4. Epub 2012 Dec 9.
PubMed 23224224Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, Mehta RL, Ambalavanan N. Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatr Res. 2011 Sep;70(3):302-6. doi: 10.1203/PDR.0b013e3182275164.
PubMed 21646940Askenazi DJ, Montesanti A, Hundley H, Koralkar R, Pawar P, Shuaib F, Liwo A, Devarajan P, Ambalavanan N. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr. 2011 Dec;159(6):907-12.e1. doi: 10.1016/j.jpeds.2011.05.045. Epub 2011 Jul 23.
PubMed 21784446Auron A, Mhanna MJ. Serum creatinine in very low birth weight infants during their first days of life. J Perinatol. 2006 Dec;26(12):755-60. doi: 10.1038/sj.jp.7211604. Epub 2006 Oct 12.
PubMed 17036033Brion LP, Fleischman AR, McCarton C, Schwartz GJ. A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: noninvasive assessment of body composition and growth. J Pediatr. 1986 Oct;109(4):698-707. doi: 10.1016/s0022-3476(86)80245-1.
PubMed 3761090Carmody JB, Charlton JR. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics. 2013 Jun;131(6):1168-79. doi: 10.1542/peds.2013-0009. Epub 2013 May 13.
PubMed 23669525Carmody JB, Swanson JR, Rhone ET, Charlton JR. Recognition and reporting of AKI in very low birth weight infants. Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2036-43. doi: 10.2215/CJN.05190514. Epub 2014 Oct 3.
PubMed 25280497Drukker A, Guignard JP. Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr. 2002 Apr;14(2):175-82. doi: 10.1097/00008480-200204000-00006.
PubMed 11981287Faa G, Gerosa C, Fanni D, Nemolato S, Locci A, Cabras T, Marinelli V, Puddu M, Zaffanello M, Monga G, Fanos V. Marked interindividual variability in renal maturation of preterm infants: lessons from autopsy. J Matern Fetal Neonatal Med. 2010 Oct;23 Suppl 3:129-33. doi: 10.3109/14767058.2010.510646.
PubMed 20836739Gadepalli SK, Selewski DT, Drongowski RA, Mychaliska GB. Acute kidney injury in congenital diaphragmatic hernia requiring extracorporeal life support: an insidious problem. J Pediatr Surg. 2011 Apr;46(4):630-635. doi: 10.1016/j.jpedsurg.2010.11.031.
PubMed 21496529Gameiro J, Branco T, Lopes JA. Artificial Intelligence in Acute Kidney Injury Risk Prediction. J Clin Med. 2020 Mar 3;9(3):678. doi: 10.3390/jcm9030678.
PubMed 32138284
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Acute Kidney Injury in Infants Exposed to Nephrotoxic Drugs: A Big Data Approach to Predict NEOnatal Acute Kidney Injury in Newborns expoSed to nephroTOxic Drugs. (NeoAKI STOP)
- ClinicalTrials.gov ID
- NCT05851222
- Acronym / sponsor ID
- NeoAKISTOP / NeoAKI STOP
- Conditions
- Acute Kidney Injury, Drug Use, Drug Interaction, Drug Toxicity, Drug-Induced Nephropathy, Machine Learning
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 4,200 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- 1 Aug 2023 (estimated)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This observational retrospective study aims to learn about the incidence of acute kidney (AKI) injury in newborns in infants exposed to nephrotoxic drugs with a big data approach.
The main question it aims to answer are:
- Develop a model that can predict the occurrence of AKI in infants admitted to the NICU;
- Identify the drug or combination of drugs associated with an increased risk of AKI.
The group of infants exposed to drugs will be defined based on exposure for at least 1-day tone one or more therapies commonly used in the NICU. Once the AKI event has occurred, the observation of the trend of daily creatinine and diuresis values will be continued for the period covered by the study.
Detailed description
- Rationale and background Acute Kidney Injury (AKI) is defined as the sudden impairment of kidney function that results in altered hydro electrolyte balance and renal waste product elimination. Extensive evidence shows that the onset of AKI in critically ill pediatric patients is associated with an increased risk of death and a longer length of hospitalization. Furthermore, in patients who survive an episode of AKI, there is an increased risk of developing long-term morbidity, particularly Chronic Kidney Disease (CKD). The neonatal kidney has numerous features on the pathophysiological level that predispose this population more to AKI than at other life ages. In addition to the peculiarities related to the development and physiology of the kidney, especially if preterm, infants admitted to the NICU are exposed to multiple risk factors that may contribute to the onset of AKI. A recent multicenter study conducted in neonatal intensive care units in Canada, Australia, India, and the United States reported an overall incidence of AKI of 29.9% and showed that the development of AKI is an independent risk factor for death and prolonged hospitalization. The incidence of AKI by gestational age also showed a typical U-shaped distribution, with the greater occurrence at the two extremes represented by infants with gestational ages >36 weeks (36.7%) and <29 weeks (47.9%), while the lowest value was recorded in the 29-36 weeks range. The risk of developing acute kidney injury is known to increase with the number of medications used (especially if > 3) and the duration of exposure, especially for the aminoglycoside antibiotic category. In addition, critically ill patients who developed AKI were generally more exposed to nephrotoxic drugs than those who did not develop AKI. In the NICU setting, it is estimated that 87% of VLBW infants are exposed to at least one nephrotoxic drug during their hospital stay, and about a quarter of these infants develop at least one episode of acute renal distress. The diagnosis of AKI is based on increased serum creatinine (SCr) or decreased urinary output. To date, the definition of acute kidney injury is based on the former Kidney Disease Improving Global Outcomes (KIDGO) criteria modified for newborns. However, in light of the premises made, it can be understood how creatinine monitoring allows only passive observation of the phenomenon, noting the rise in creatinine values when renal insult has already occurred by then. This allows only retrospective changes in some aspects of the infant's management, such as optimizing fluid intake, suspending the administration of nephrotoxic drugs, and correcting any electrolyte imbalances, but without being able to prevent the onset of AKI. Ideally, the investigators should be able to understand and predict how different risk factors contribute to the beginning of renal damage in a given patient, thus allowing individualized management. Given the complexity of patients admitted to the NICU and the number of variables in the field, the problem lends itself well to analysis through AI and general statistical inference methods. Such methods have previously been used successfully for studies on adult patients but, to our knowledge, never on newborn patients. The investigators hope to apply these models in a prospective cohort study to validate their use and develop a real-time monitoring system of the kidney well-being of our nephrotoxic drug-exposed infants that can guide the clinician in patient management. Indeed, systematic surveillance of at-risk patients can significantly reduce the onset of kidney damage and limit both short-term and long-term consequences, thereby improving neonatal outcomes.
- Research question and objectives 2.1 Primary objectives
- Develop a model that can predict the occurrence of AKI in infants admitted to the NICU;
- Identify the drug or combination associated with an increased risk of AKI. 2.2 Secondary objectives
- Identify subgroups of patients at increased risk of AKI;
- Identify time windows at increased risk of AKI during NICU admission.
- Methods 3.1 Study design Single-center retrospective observational cohort study at the UOC of Neonatology and Neonatal Intensive Care Unit of Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 3.1.1 Primary endpoints
- Development of AKI defined according to modified KIDGO criteria for the newborn based on increased serum creatinine values or reduced mean hourly diuresis during NICU admission. 3.1.2 Secondary endpoints
- Number of AKI cases in risk subcategories: very low birth weight (birth weight < 1500 g), extremely low birth weight (birth weight < 1000 g), cardiopathic, with surgical pathology, sepsis, asphyxia;
- Number of AKI cases in the first week of hospitalization compared with other periods.
- Setting A population of infants admitted to the NICU of the Foundation will be retrospectively considered. 4.1 Study population The study population will consist of patients born between January 2010 and December 2022.
- Inclusion criteria
- Patients who meet all of the following criteria will be included in the study:
- born between 01/01/2010 and 31/12/2022;
- admitted within 24 hours of birth in the NICU (both inborn and outborn);
- availability of at least two serum creatinine values or a daily hourly diuresis assessment in the first 30 days of life.
- Exclusion Criteria Patients who meet even one of the following criteria will be excluded:
- pre- or postnatal diagnosis of severe urologic and/or nephrologic pathology on a malformative and/or genetic basis;
- finding of serum creatinine > 2 mg/dl in the first 24 hours of life;
- genetic conditions that may impact patient survival or renal function;
- length of stay in the NICU less than 48 hours (death or transfer to another department);
- infants undergoing ECMO.
- Variables Clinical and instrumental data regarding each patient's medical history will be acquired for the NICU admission by the first month of life. Definition of AKI All available serum creatinine values for each patient during the NICU admission will be recorded, considering that determinations made within the first 48 hours of the infant's life are affected by maternal creatinine values. The presence of AKI will be determined according to the modified KIDGO criteria for the newborn, as reported in previous work in the neonatal setting. Exposure to drugs. The group of infants exposed to drugs will be defined based on exposure for at least 1-day tone one or more therapies commonly used in the NICU. Special attention will be given to exposure to antibiotics, antivirals, antifungals, diuretics, anti-inflammatories, inotropes, and vasopressors. In addition to the active ingredient, other significant data such as prescribed dose, administration route, treatment duration, and temporal relationship between treatment and diagnosis of AKI will also be considered. Once the AKI event has occurred, the observation of the trend of daily creatinine and diuresis values will be continued for the period covered by the study.
- Source documents Data will be collected from each newborn's Neocare electronic medical record (GPI SpA).
- Sample size Approximately 600 newborns are admitted to the neonatal intensive care unit each year. The incidence of renal damage in the critically ill newborn population is reported in the literature to be approximately 30%. In light of these considerations, over the decade of our observation, the estimated number of infants admitted to the NICU is about 6000 patients. Assuming a 30% drop-out related to exclusion criteria (about 1800 subjects), the investigators expect to be able to include approximately 4200 subjects in the study, among whom the investigators should find about 1200 cases of acute renal damage.
- Data management Data will be collected anonymously by assigning a code to each patient. They will then be organized and stored on data storage systems with secure access.
- Data Analysis Data will be analyzed using statistical inference approaches peculiar to Data Science and Artificial Intelligence (AI), such as Decision Trees, Logistic Regression, and Machine Learning (ML). The data themselves will suggest the choice of methods used.
- Primary endpoint: analysis Identifying patterns or items in the administration of so-called off-label drugs in the neonatal patient (premature or not) and the development of renal syndromes related to the administration of the drug itself. Once one or more correlation factors have been identified, they could be entered within the Electronic Medical Record system (and in particular within the Clinical Decision Support System) in order to be able to alert the treating clinical staff of any clinical risk associated with the administration.
- Secondary endpoint: analysis Development of a computational Early Warning model for AKI that ensures the interpretability of the prediction.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patients admitted to NICU and born between January 2010 and December 2022
Key inclusion criteria (3 listed)
- born between 01/01/2010 and 31/12/2022;
- admitted within 24 hours of birth in the NICU (both inborn and outborn);
- availability of at least two serum creatinine values or a daily hourly diuresis assessment in the first 30 days of life.
Key exclusion criteria (5 listed)
- pre- or postnatal diagnosis of severe urologic and/or nephrologic pathology on a malformative and/or genetic basis;
- finding of serum creatinine > 2 mg/dl in the first 24 hours of life;
- genetic conditions that may impact patient survival or renal function;
- length of stay in the NICU less than 48 hours (death or transfer to another department);
- infants undergoing ECMO.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Develop a model that can predict the occurrence of AKI in infants admitted to the NICU;
Time frame: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
All available serum creatinine values for each patient during the NICU admission will be recorded, considering that determinations made within the first 48 hours of the infant's life are affected by maternal creatinine values. The presence of AKI will be determined according to the modified KIDGO criteria for the newborn, as reported in previous work in the neonatal setting (Jetton JG, 2017; Jetton JG and Askenazi DJ, 2012; Stoops C, 2016; Askenazi DJ, Patil NR, et al., 2015; Sarkar S, 2014).
Identify the drug or combination of drugs associated with an increased risk of AKI
Time frame: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
The group of infants exposed to drugs will be defined based on exposure for at least 1-day tone one or more therapies commonly used in the NICU. Special attention will be given to exposure to antibiotics, antivirals, antifungals, diuretics, anti-inflammatories, inotropes, and vasopressors. In addition to the active ingredient, other significant data such as prescribed dose, administration route, treatment duration, and temporal relationship between treatment and diagnosis of AKI will also be considered.
2 secondary outcomes
Identify subgroups of patients at increased risk of AKI
Time frame: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
Identify time windows at increased risk of AKI during NICU admission.
Time frame: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Results publication: PubMed 24607244Abitbol CL, Seeherunvong W, Galarza MG, Katsoufis C, Francoeur D, Defreitas M, Edwards-Richards A, Master Sankar Raj V, Chandar J, Duara S, Yasin S, Zilleruelo G. Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate? J Pediatr. 2014 May;164(5):1026-1031.e2. doi: 10.1016/j.jpeds.2014.01.044. Epub 2014 Mar 5.
- Results publication: PubMed 25808019Askenazi D, Patil NR, Ambalavanan N, Balena-Borneman J, Lozano DJ, Ramani M, Collins M, Griffin RL. Acute kidney injury is associated with bronchopulmonary dysplasia/mortality in premature infants. Pediatr Nephrol. 2015 Sep;30(9):1511-8. doi: 10.1007/s00467-015-3087-5. Epub 2015 Mar 26.
- Results publication: PubMed 16374442Askenazi DJ, Feig DI, Graham NM, Hui-Stickle S, Goldstein SL. 3-5 year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int. 2006 Jan;69(1):184-9. doi: 10.1038/sj.ki.5000032.
- Results publication: PubMed 22424940Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, Ambalavanan N. Urine biomarkers predict acute kidney injury in newborns. J Pediatr. 2012 Aug;161(2):270-5.e1. doi: 10.1016/j.jpeds.2012.02.007. Epub 2012 Mar 16.
- Results publication: PubMed 23224224Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Patil N, Ambalavanan N. Fluid overload and mortality are associated with acute kidney injury in sick near-term/term neonate. Pediatr Nephrol. 2013 Apr;28(4):661-6. doi: 10.1007/s00467-012-2369-4. Epub 2012 Dec 9.
- Results publication: PubMed 21646940Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, Mehta RL, Ambalavanan N. Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatr Res. 2011 Sep;70(3):302-6. doi: 10.1203/PDR.0b013e3182275164.
- Results publication: PubMed 21784446Askenazi DJ, Montesanti A, Hundley H, Koralkar R, Pawar P, Shuaib F, Liwo A, Devarajan P, Ambalavanan N. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr. 2011 Dec;159(6):907-12.e1. doi: 10.1016/j.jpeds.2011.05.045. Epub 2011 Jul 23.
- Results publication: PubMed 17036033Auron A, Mhanna MJ. Serum creatinine in very low birth weight infants during their first days of life. J Perinatol. 2006 Dec;26(12):755-60. doi: 10.1038/sj.jp.7211604. Epub 2006 Oct 12.
- Results publication: PubMed 3761090Brion LP, Fleischman AR, McCarton C, Schwartz GJ. A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: noninvasive assessment of body composition and growth. J Pediatr. 1986 Oct;109(4):698-707. doi: 10.1016/s0022-3476(86)80245-1.
- Results publication: PubMed 23669525Carmody JB, Charlton JR. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics. 2013 Jun;131(6):1168-79. doi: 10.1542/peds.2013-0009. Epub 2013 May 13.
- Results publication: PubMed 25280497Carmody JB, Swanson JR, Rhone ET, Charlton JR. Recognition and reporting of AKI in very low birth weight infants. Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2036-43. doi: 10.2215/CJN.05190514. Epub 2014 Oct 3.
- Results publication: PubMed 11981287Drukker A, Guignard JP. Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr. 2002 Apr;14(2):175-82. doi: 10.1097/00008480-200204000-00006.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giacomo Cavallaro, MD, PhD study director
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Ilaria Amodeo, MD principal investigator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Kidney Injury and Drug Use, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giacomo Cavallaro, MD, PhD (+390255032234, giacomo.cavallaro@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Develop a model that can predict the occurrence of AKI in infants admitted to the NICU; (time frame: From the date of randomization until the date of the first documented progression of AKI and up to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05851222, which also lists 44 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.