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

Hearing Loss Clinical Trial

— AURORA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03253614
• Other study ID #: REK Nord 2016/1786
• Status: Completed
• Start date: September 15, 2017
• Est. completion date: September 15, 2018

Study information

• Verified date: March 2019
• Source: University Hospital of North Norway
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: September 15, 2018
• Est. primary completion date: September 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Gentamicin Adverse Reaction
• Hearing Loss
• Renal Tubular Disorder

Intervention

Diagnostic Test:
• Audiometry
Extended high-frequency (EHF; 9-16 kHz) audiometry
• Urine biomarkers for renal tubular function
Kidney Injury Molecule-1
• Blood pressure
Blood pressure right arm, measured With standard Methods 3 times

Locations

Country	Name	City	State
Norway	University Hospital of North Norway	Tromsø

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of North Norway

Country where clinical trial is conducted

Norway, 

References & Publications (2)

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] — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hearing threshold in the extended high-frequency range	kHz	Baseline
Secondary	Urine biomarkers	Kidney injury molecule-1	Baseline
Secondary	Blood pressure right arm	mm Hg	Baseline
Secondary	Hearing threshold in the normal frequency range	kHz	Baseline