<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03253614</url>
  </required_header>
  <id_info>
    <org_study_id>REK Nord 2016/1786</org_study_id>
    <nct_id>NCT03253614</nct_id>
  </id_info>
  <brief_title>Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)</brief_title>
  <acronym>AURORA</acronym>
  <official_title>Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA-study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital of North Norway</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital of North Norway</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gentamicin, in combination with a beta-lactam antibiotic, is commonly used for treatment of&#xD;
      neonatal sepsis. Neonates have a high volume of distribution. It is a paradox that most&#xD;
      neonatal dosing schedules still recommend lower gentamicin doses (4-5 mg/kg) than in older&#xD;
      children (≥ 7 mg/kg). In the neonatal unit in Tromsø a simplified gentamicin high-dose (6&#xD;
      mg/kg) regimen has been in use since 2004.&#xD;
&#xD;
      The investigators have previously shown that this regimen was associated with low number of&#xD;
      elevated trough levels, low numbers of prescription errors and no evidence for ototoxicity in&#xD;
      the immediate neonatal period. However, the long-term safety of gentamicin therapy in&#xD;
      neonates is not well studied when it comes to ototoxicity and possible nephrotoxicity.&#xD;
&#xD;
      The objective of the current study is therefore to perform a detailed hearing evaluation,&#xD;
      including an extended high-frequency (EHF; 9-16 kHz) audiometry, in a follow-up study of&#xD;
      children (participants) aged 6-15 years who were exposed to a high-dose gentamicin regimen in&#xD;
      the neonatal period. Moreover, we will investigate blood pressure and urine biomarkers to&#xD;
      assess renal tubular function. The aim is to include 250 children exposed to gentamicin in&#xD;
      the neonatal period and a control group of 25 healthy children.&#xD;
&#xD;
      EHF audiometry is a more sensitive method for detecting ototoxic damage and provides evidence&#xD;
      of ototoxicity before any hearing loss is detected by conventional systems. This is the&#xD;
      background for choice of method.&#xD;
&#xD;
      The primary outcome is the difference in average hearing threshold in the EHF range between&#xD;
      the control group and the exposed group.&#xD;
&#xD;
      Secondary outcomes are i) difference in average hearing threshold in the EHF range between&#xD;
      the children with gentamicin trough levels &gt; 1.0 mg/L versus those who had lower trough&#xD;
      levels, ii) markers of renal tubular function (kidney injury molecule 1) and iii) blood&#xD;
      pressure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">September 15, 2018</completion_date>
  <primary_completion_date type="Actual">September 15, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Hearing threshold in the extended high-frequency range</measure>
    <time_frame>Baseline</time_frame>
    <description>kHz</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urine biomarkers</measure>
    <time_frame>Baseline</time_frame>
    <description>Kidney injury molecule-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure right arm</measure>
    <time_frame>Baseline</time_frame>
    <description>mm Hg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hearing threshold in the normal frequency range</measure>
    <time_frame>Baseline</time_frame>
    <description>kHz</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">226</enrollment>
  <condition>Hearing Loss</condition>
  <condition>Gentamicin Adverse Reaction</condition>
  <condition>Renal Tubular Disorder</condition>
  <arm_group>
    <arm_group_label>Exposed group</arm_group_label>
    <description>250 children aged 6-15 years exposed to gentamicin in the neonatal period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Audiometry</intervention_name>
    <description>Extended high-frequency (EHF; 9-16 kHz) audiometry</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Exposed group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Urine biomarkers for renal tubular function</intervention_name>
    <description>Kidney Injury Molecule-1</description>
    <arm_group_label>Exposed group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood pressure</intervention_name>
    <description>Blood pressure right arm, measured With standard Methods 3 times</description>
    <arm_group_label>Exposed group</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urine biomarkers&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children aged 6-15 years and Exposed to gentamicin therapy in the neonatal period and&#xD;
        treated at neonatal unit at the University Hospital of North Norway.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Exposed to gentamicin therapy in the neonatal period and treated at neonatal unit at&#xD;
             the University Hospital of North Norway&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not able to cooperate during an audiometry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claus Klingenberg, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of North Norway</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of North Norway</name>
      <address>
        <city>Tromsø</city>
        <zip>N-9038</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>24233331</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>23557866</PMID>
  </reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>March 6, 2019</last_update_submitted>
  <last_update_submitted_qc>March 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital of North Norway</investigator_affiliation>
    <investigator_full_name>Claus Klingenberg</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hearing Loss</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Data will be made available after publication of the first scientific report. Sharing of data will be done after a signed agreement.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03253614
org study id: REK Nord 2016/1786
nct id: NCT03253614
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Cohort
time perspective: Prospective
measure: Hearing threshold in the extended high-frequency range
time frame: Baseline
description: kHz
measure: Urine biomarkers
time frame: Baseline
description: Kidney injury molecule-1
measure: Blood pressure right arm
time frame: Baseline
description: mm Hg
measure: Hearing threshold in the normal frequency range
time frame: Baseline
description: kHz
arm group label: Exposed group
description: 250 children aged 6-15 years exposed to gentamicin in the neonatal period
arm group label: Control group
description: 25 healthy children aged 6-15 years NOT exposed to gentamicin in the neonatal period
intervention type: Diagnostic Test
intervention name: Audiometry
description: Extended high-frequency (EHF; 9-16 kHz) audiometry
arm group label: Control group
arm group label: Exposed group
intervention type: Diagnostic Test
intervention name: Urine biomarkers for renal tubular function
description: Kidney Injury Molecule-1
arm group label: Exposed group
intervention type: Diagnostic Test
intervention name: Blood pressure
description: Blood pressure right arm, measured With standard Methods 3 times
arm group label: Exposed group
Urine biomarkers
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 5 Years
maximum age: 15 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Claus Klingenberg, MD, PhD
role: Principal Investigator
affiliation: University Hospital of North Norway
facility: 
country: Norway
citation: 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.
PMID: 24233331
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.
PMID: 23557866
responsible party type: Principal Investigator
investigator affiliation: University Hospital of North Norway
investigator full name: Claus Klingenberg
investigator title: Professor
mesh term: Hearing Loss
sharing ipd: Undecided
ipd description: Data will be made available after publication of the first scientific report. Sharing of data will be done after a signed agreement.