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CompletedNCT03253614AURORAUpdated Mar 7, 2019

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

An observational study in Hearing Loss, Gentamicin Adverse Reaction and Renal Tubular Disorder, sponsored by University Hospital of North Norway. Completed at 1 site in Norway. Open to participants aged 5 Years to 15 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-03-07.

Sponsored by University Hospital of North Norway · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
226
Ages
5 Years to 15 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Hearing Loss
  • Gentamicin Adverse Reaction
  • Renal Tubular Disorder

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03

Who can participate

Ages eligible
5 Years to 15 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
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.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  • Not able to cooperate during an audiometry
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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
226 participants (actual)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • Exposed group

    250 children aged 6-15 years exposed to gentamicin in the neonatal period

    Diagnostic Test: Audiometry · Diagnostic Test: Urine biomarkers for renal tubular function · Diagnostic Test: Blood pressure

  • Control group

    25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period

    Diagnostic Test: Audiometry

Interventions

  • Diagnostic testAudiometry

    Extended high-frequency (EHF; 9-16 kHz) audiometry

  • Diagnostic testUrine biomarkers for renal tubular function

    Kidney Injury Molecule-1

  • Diagnostic testBlood pressure

    Blood pressure right arm, measured With standard Methods 3 times

05

What researchers measure

Primary outcomes

  1. Hearing threshold in the extended high-frequency range

    kHz

    Time frame: Baseline

Secondary outcomes

  1. Urine biomarkers

    Kidney injury molecule-1

    Time frame: Baseline

  2. Blood pressure right arm

    mm Hg

    Time frame: Baseline

  3. Hearing threshold in the normal frequency range

    kHz

    Time frame: Baseline

06

Study locations

1 site
  • University Hospital of North Norway
    Tromsø, N-9038, Norway
07

References and documents

Publications

  • 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. PubMed 24233331 ↗
  • 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. PubMed 23557866 ↗
  • 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. PubMed 34917565 ↗
  • 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. PubMed 33838463 ↗
  • 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. PubMed 31915192 ↗

Individual participant data

Plan to share: Undecided — Data will be made available after publication of the first scientific report. Sharing of data will be done after a signed agreement.

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Registry details

Key details

Study ID
NCT03253614
Lead sponsor
University Hospital of North Norway
Responsible party
Claus Klingenberg (Professor, University Hospital of North Norway) — Principal investigator
First posted
Aug 18, 2017
Start date
Sep 15, 2017
Primary completion
Sep 15, 2018
Completion
Sep 15, 2018
Last update
Mar 7, 2019

Study contacts

Claus Klingenberg, MD, PhD
principal investigator · University Hospital of North Norway

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.

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