Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)
AURORA
1 other identifier
observational
226
1 country
1
Brief Summary
Gentamicin, in combination with a beta-lactam antibiotic, is commonly used for treatment of neonatal sepsis. Neonates have a high volume of distribution. It is a paradox that most neonatal dosing schedules still recommend lower gentamicin doses (4-5 mg/kg) than in older children (≥ 7 mg/kg). In the neonatal unit in Tromsø a simplified gentamicin high-dose (6 mg/kg) regimen has been in use since 2004. The investigators have previously shown that this regimen was associated with low number of elevated trough levels, low numbers of prescription errors and no evidence for ototoxicity in the immediate neonatal period. However, the long-term safety of gentamicin therapy in neonates is not well studied when it comes to ototoxicity and possible nephrotoxicity. The objective of the current study is therefore to perform a detailed hearing evaluation, including an extended high-frequency (EHF; 9-16 kHz) audiometry, in a follow-up study of children (participants) aged 6-15 years who were exposed to a high-dose gentamicin regimen in the neonatal period. Moreover, we will investigate blood pressure and urine biomarkers to assess renal tubular function. The aim is to include 250 children exposed to gentamicin in the neonatal period and a control group of 25 healthy children. EHF audiometry is a more sensitive method for detecting ototoxic damage and provides evidence of ototoxicity before any hearing loss is detected by conventional systems. This is the background for choice of method. The primary outcome is the difference in average hearing threshold in the EHF range between the control group and the exposed group. Secondary outcomes are i) difference in average hearing threshold in the EHF range between the children with gentamicin trough levels \> 1.0 mg/L versus those who had lower trough levels, ii) markers of renal tubular function (kidney injury molecule 1) and iii) blood pressure.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Sep 2017
Shorter than P25 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 14, 2017
CompletedFirst Posted
Study publicly available on registry
August 18, 2017
CompletedStudy Start
First participant enrolled
September 15, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 15, 2018
CompletedMarch 7, 2019
March 1, 2019
1 year
August 14, 2017
March 6, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Hearing threshold in the extended high-frequency range
kHz
Baseline
Secondary Outcomes (3)
Urine biomarkers
Baseline
Blood pressure right arm
Baseline
Hearing threshold in the normal frequency range
Baseline
Study Arms (2)
Exposed group
250 children aged 6-15 years exposed to gentamicin in the neonatal period
Control group
25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period
Interventions
Extended high-frequency (EHF; 9-16 kHz) audiometry
Blood pressure right arm, measured With standard Methods 3 times
Eligibility Criteria
Children aged 6-15 years and Exposed to gentamicin therapy in the neonatal period and treated at neonatal unit at the University Hospital of North Norway.
You may qualify if:
- Exposed to gentamicin therapy in the neonatal period and treated at neonatal unit at the University Hospital of North Norway
You may not qualify if:
- Not able to cooperate during an audiometry
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University Hospital of North Norway
Tromsø, N-9038, Norway
Related Publications (5)
Fjalstad JW, Laukli E, van den Anker JN, Klingenberg C. High-dose gentamicin in newborn infants: is it safe? Eur J Pediatr. 2013 Nov 14. doi: 10.1007/s00431-013-2194-1. Online ahead of print.
PMID: 24233331BACKGROUNDSetiabudy R, Suwento R, Rundjan L, Yasin FH, Louisa M, Dwijayanti A, Simanjuntak E. Lack of a relationship between the serum concentration of aminoglycosides and ototoxicity in neonates. Int J Clin Pharmacol Ther. 2013 May;51(5):401-6. doi: 10.5414/CP201833.
PMID: 23557866BACKGROUNDRypdal V, Jorandli S, Hemmingsen D, Solbu MD, Klingenberg C. Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity. Front Pediatr. 2021 Nov 30;9:779827. doi: 10.3389/fped.2021.779827. eCollection 2021.
PMID: 34917565DERIVEDHemmingsen D, Stenklev NC, Klingenberg C. Extended high frequency audiometry thresholds in healthy school children. Int J Pediatr Otorhinolaryngol. 2021 May;144:110686. doi: 10.1016/j.ijporl.2021.110686. Epub 2021 Mar 23.
PMID: 33838463DERIVEDHemmingsen D, Mikalsen C, Hansen AR, Fjalstad JW, Stenklev NC, Klingenberg C. Hearing in Schoolchildren After Neonatal Exposure to a High-Dose Gentamicin Regimen. Pediatrics. 2020 Feb;145(2):e20192373. doi: 10.1542/peds.2019-2373. Epub 2020 Jan 8.
PMID: 31915192DERIVED
Biospecimen
Urine biomarkers
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Claus Klingenberg, MD, PhD
University Hospital of North Norway
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
August 14, 2017
First Posted
August 18, 2017
Study Start
September 15, 2017
Primary Completion
September 15, 2018
Study Completion
September 15, 2018
Last Updated
March 7, 2019
Record last verified: 2019-03