Clinical trial NCT03253614: Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)
Official title: Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA-study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hearing Loss
Gentamicin Adverse Reaction
Renal Tubular Disorder
Lead sponsor: University Hospital of North Norway
Sponsor class: OTHER
First posted: 2017-08-18
Enrollment: 226
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

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.


Eligibility criteria: Inclusion Criteria:

* Exposed to gentamicin therapy in the neonatal period and treated at neonatal unit at the University Hospital of North Norway

Exclusion Criteria:

* Not able to cooperate during an audiometry

Primary outcomes:
measure: Hearing threshold in the extended high-frequency range
timeFrame: Baseline
Secondary outcomes:
measure: Urine biomarkers
timeFrame: Baseline
measure: Blood pressure right arm
timeFrame: Baseline
measure: Hearing threshold in the normal frequency range
timeFrame: Baseline
Other outcomes:
Locations:
city: Tromsø
country: Norway
facility: University Hospital of North Norway
Study officials:
affiliation: University Hospital of North Norway
name: Claus Klingenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Setiabudy 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.
citation: Rypdal 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.
citation: Hemmingsen 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.
citation: Hemmingsen 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.