Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)

Study Overview
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Brief Summary
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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.

Official Title
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Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA-study)

Conditions
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Hearing Loss, Gentamicin Adverse Reaction, Renal Tubular Disorder

Intervention / Treatment
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* Diagnostic Test: Audiometry
* Diagnostic Test: Urine biomarkers for renal tubular function
* Diagnostic Test: Blood pressure


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed group<br>250 children aged 6-15 years exposed to gentamicin in the neonatal period | Diagnostic Test: Audiometry<br>* Extended high-frequency (EHF; 9-16 kHz) audiometry<br>Diagnostic Test: Urine biomarkers for renal tubular function<br>* Kidney Injury Molecule-1<br>Diagnostic Test: Blood pressure<br>* Blood pressure right arm, measured With standard Methods 3 times<br>|
| Control group<br>25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period | Diagnostic Test: Audiometry<br>* Extended high-frequency (EHF; 9-16 kHz) audiometry<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hearing threshold in the extended high-frequency range | kHz | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine biomarkers | Kidney injury molecule-1 | Baseline | 
| Blood pressure right arm | mm Hg | Baseline | 
| Hearing threshold in the normal frequency range | kHz | Baseline |