Hearing LossAURORANCT03253614
Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)
An observational study of Hearing Loss and Gentamicin Adverse Reaction, run by University Hospital of North Norway at 1 site in Norway.
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). Read more about this study
- Who is it for?
- Ages 5 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Hearing Loss, Gentamicin Adverse Reaction, Renal Tubular Disorder
- What is being tested?
- Audiometry, Urine biomarkers for renal tubular function and Blood pressure
- How many people
- 226 participants
- Where
- 1 siteNorway
- Study dates
- 15 Sep 2017to 15 Sep 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- Exposed to gentamicin therapy in the neonatal period and treated at neonatal unit at the University Hospital of North Norway
Who cannot join
- Not able to cooperate during an audiometry
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA-study)
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.
Read more
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.
- Being tested
- Audiometry, Urine biomarkers for renal tubular function, Blood pressure
- Medical subject headings
- Hearing Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AudiometryDiagnostic test
Extended high-frequency (EHF; 9-16 kHz) audiometry
Urine biomarkers for renal tubular functionDiagnostic test
Kidney Injury Molecule-1
Blood pressureDiagnostic test
Blood pressure right arm, measured With standard Methods 3 times
| Study group | Role | What they receive |
|---|---|---|
| Exposed group | 250 children aged 6-15 years exposed to gentamicin in the neonatal period Receives: 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 Receives: Diagnostic Test: Audiometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hearing threshold in the extended high-frequency range
kHz
Measured: Baseline
Secondary outcomes (3)
Urine biomarkers
Kidney injury molecule-1
Measured: Baseline
Blood pressure right arm
mm Hg
Measured: Baseline
Hearing threshold in the normal frequency range
kHz
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2017
- Study start15 Sep 2017
- Primary completion15 Sep 2018
- Study completion15 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hearing LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital of North Norway
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Claus Klingenberg, University Hospital of North Norway
- Investigators
- Claus Klingenberg, MD, PhD, Principal investigator, University Hospital of North Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03253614
- Sponsor's protocol ID
- REK Nord 2016/1786
- Acronym
- AURORA
- Status last verified
- Mar 2019
- First submitted
- 14 Aug 2017
- Last updated
- 7 Mar 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data will be made available after publication of the first scientific report. Sharing of data will be done after a signed agreement.
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 24233331Setiabudy 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 23557866Rypdal 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 34917565Hemmingsen 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 33838463Hemmingsen 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA-study)
- ClinicalTrials.gov ID
- NCT03253614
- Acronym / sponsor ID
- AURORA / REK Nord 2016/1786
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- University Hospital of North NorwayUniversity, hospital or other
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- 15 Sep 2018 (actual)
- Study completion
- 15 Sep 2018 (actual)
- First posted
- 18 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed group | – | Diagnostic Test: Audiometry, Diagnostic Test: Urine biomarkers for renal tubular function, Diagnostic Test: Blood pressure250 children aged 6-15 years exposed to gentamicin in the neonatal period |
| Control group | – | Diagnostic Test: Audiometry25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (1 listed)
- Exposed to gentamicin therapy in the neonatal period and treated at neonatal unit at the University Hospital of North Norway
Key exclusion criteria (1 listed)
- Not able to cooperate during an audiometry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AudiometryExtended high-frequency (EHF; 9-16 kHz) audiometry | Diagnostic test | Control group, Exposed group |
| Urine biomarkers for renal tubular functionKidney Injury Molecule-1 | Diagnostic test | Exposed group |
| Blood pressureBlood pressure right arm, measured With standard Methods 3 times | Diagnostic test | Exposed group |
Primary outcome
Hearing threshold in the extended high-frequency range
Time frame: Baseline
kHz
3 secondary outcomes
Urine biomarkers
Time frame: Baseline
Blood pressure right arm
Time frame: Baseline
Hearing threshold in the normal frequency range
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2019.
- Background: PubMed 24233331Fjalstad 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.
- Background: PubMed 23557866Setiabudy 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.
- Derived from this study: PubMed 34917565Rypdal 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.
- Derived from this study: PubMed 33838463Hemmingsen 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.
- Derived from this study: PubMed 31915192Hemmingsen 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.
- Individual participant dataSharing planned: 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claus Klingenberg, MD, PhD principal investigator
University Hospital of North Norway
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hearing Loss and Gentamicin Adverse Reaction, run by University Hospital of North Norway at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hearing threshold in the extended high-frequency range (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03253614, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2019.