Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Exposed group 250 children aged 6-15 years exposed to gentamicin in the neonatal period |
Diagnostic Test: Audiometry
Extended high-frequency (EHF; 9-16 kHz) audiometry
Diagnostic Test: Urine biomarkers for renal tubular function
Kidney Injury Molecule-1
Diagnostic Test: Blood pressure
Blood pressure right arm, measured With standard Methods 3 times
|
| Control group 25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period |
Diagnostic Test: Audiometry
Extended high-frequency (EHF; 9-16 kHz) audiometry
|
Outcome Measures
Primary Outcome Measures
- Hearing threshold in the extended high-frequency range [Baseline]
kHz
Secondary Outcome Measures
- Urine biomarkers [Baseline]
Kidney injury molecule-1
- Blood pressure right arm [Baseline]
mm Hg
- Hearing threshold in the normal frequency range [Baseline]
kHz
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital of North Norway | Tromsø | Norway | N-9038 |
Sponsors and Collaborators
- University Hospital of North Norway
Investigators
- Principal Investigator: Claus Klingenberg, MD, PhD, University Hospital of North Norway
Study Documents (Full-Text)
None provided.More Information
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. [Epub ahead of print]
- 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.
- REK Nord 2016/1786