<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/NCT02967432</url>
  </required_header>
  <id_info>
    <org_study_id>Crouse Hospital 2016.0125</org_study_id>
    <nct_id>NCT02967432</nct_id>
  </id_info>
  <brief_title>Mupirocin to Reduce Staphylococcus Aureus Colonization in Infants Hospitalized in a NICU</brief_title>
  <official_title>Randomized Controlled Trial of Mupirocin to Reduce Staphylococcus Aureus Colonization in Infants Hospitalized in a Neonatal Intensive Care Unit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Crouse Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jana Shaw, MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Steven Gross, MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>David Martin, RN</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dale Franz, RPh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rachel Carey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Crouse Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether or not mupirocin treatment results in S.&#xD;
      aureus decolonization in affected NICU patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized controlled trial of mupirocin treatment of MSSA- and MRSA-colonized infants&#xD;
      aims to determine whether or not mupirocin treatment results in S. aureus decolonization in&#xD;
      affected NICU patients. MSSA- or MRSA-colonized patients who enroll in the study will be&#xD;
      randomized to either a treatment group (treatment with mupirocin) or control group (treatment&#xD;
      with placebo). A combination of active surveillance and targeted decolonization will&#xD;
      qualitatively and quantitatively enable assessment of any changes in S. aureus colonization&#xD;
      in study patients. The primary outcome measure will be the number of MSSA/MRSA patient&#xD;
      colonization days in the treatment versus control groups. Secondary outcome measures will&#xD;
      include the proportion of persistently colonized patients at each subsequent weekly screening&#xD;
      interval in the treatment versus control group, incidence and timing of MSSA/MRSA&#xD;
      recolonization in the treatment group, incidence of invasive infections with S. aureus in the&#xD;
      treatment versus control group, incidence of mupirocin-resistance in treatment versus control&#xD;
      group, and incidence of MSSA/MRSA colonization after NICU discharge in the treatment versus&#xD;
      control group.&#xD;
&#xD;
      STUDY PROCEDURES&#xD;
&#xD;
      Current standard of care in the NICU includes active universal screening of all admitted&#xD;
      patients weekly for MSSA/MRSA colonization and contact precautions for MRSA-positive&#xD;
      patients. No universal or targeted decolonization procedures are currently utilized. NICU&#xD;
      patients who screen positive for MSSA/MRSA colonization will be approached for participation&#xD;
      in this study and consent will be obtained from a parent within 2 days of the initial&#xD;
      positive screening result by a neonatologist. At time of enrollment, patients will be&#xD;
      randomized to either the treatment or control group. The pharmacy team will assign&#xD;
      randomization; all NICU staff will be blinded to the patient's study group assignments&#xD;
      throughout their admission. The treatment group will receive mupirocin ointment applied twice&#xD;
      daily inside the nares and to the skin around the umbilicus for five days. The control group&#xD;
      will receive a placebo ointment (petroleum jelly) applied in an identical fashion. The&#xD;
      control group will not receive mupirocin ointment at any time, regardless of colonization&#xD;
      status. If patients have recurrent positive MSSA/MRSA screens during the study, they may&#xD;
      receive additional identical courses of treatment with either mupirocin or placebo based on&#xD;
      their study group assignment.&#xD;
&#xD;
      The mupirocin and placebo petroleum jelly ointments will be supplied by the Crouse Hospital&#xD;
      pharmacy and sent to the NICU daily for twice daily application by the nursing staff. Both&#xD;
      groups will receive a ½ inch ribbon topical application of mupirocin or petroleum jelly&#xD;
      ointment according to their assignment around the umbilicus and a ½ inch ribbon inside each&#xD;
      nare. The neonatal nursing staff will receive appropriate education regarding the application&#xD;
      technique and study protocol prior to study initiation. The cost of the mupirocin and placebo&#xD;
      ointments will be paid for by Neonatal Associates of Central New York, LLC, and patients will&#xD;
      not receive any fee for this service.&#xD;
&#xD;
      Colonization with MSSA/MRSA will be screened weekly on Mondays, in line with current Crouse&#xD;
      Hospital NICU standard of care. MSSA/MRSA screening is performed by polymerase chain reaction&#xD;
      (PCR). Sample collection involves swabbing an infant's nares, umbilicus, and groin with a&#xD;
      cotton-tipped applicator. The swab tip is then sent to the Crouse Hospital Laboratory for&#xD;
      Staphylococcus species identification. There will be no additional costs associated with&#xD;
      these screenings, as this is already standard of care. Mupirocin resistance will be assessed&#xD;
      by disk diffusion assay with E-test methodology to determine MICs. The costs associated with&#xD;
      this additional test will be paid for by Neonatal Associates of Central New York, LLC, and&#xD;
      patients will not receive any fee for this service. An additional MSSA/MRSA screen will be&#xD;
      performed approximately 2 months after discharge at a patient's primary care physicians'&#xD;
      office visit. Sample collection procedures will be identical to the screens performed at&#xD;
      Crouse, and the screens will be sent to Laboratory Alliance of Central New York's&#xD;
      Microbiology Department for testing. Results will be made available to the principal&#xD;
      investigator. The costs associated with this additional outpatient screening test will be&#xD;
      paid for by Neonatal Associates of Central New York, LLC, and patients will not receive any&#xD;
      fee for this service.&#xD;
&#xD;
      Routine Crouse Hospital NICU policies regarding the use of contact precautions for any MRSA&#xD;
      colonized infant will continue during the study period. If an infant enrolled in the study&#xD;
      displays signs or symptoms concerning for infection, diagnostic evaluation and treatment will&#xD;
      be guided by the attending neonatologist, not deviating from the current NICU standard of&#xD;
      care. Parents are notified if their infant screens positive for MRSA colonization and if any&#xD;
      diagnostic evaluation was performed on their infant. Current standards of infection&#xD;
      prevention, such as aggressive and consistent hand hygiene, sterile procedure policies, etc.&#xD;
      will be continued during this study.&#xD;
&#xD;
      Baseline patient demographics and clinical characteristics and outcomes will be collected on&#xD;
      every study subject, including: birth weight, sex, gestational age, birth hospital, mode of&#xD;
      delivery, maternal age, length of rupture of membranes, chorioamnionitis, documented maternal&#xD;
      MRSA history when available, maternal antibiotic exposure, maternal drug abuse history,&#xD;
      respiratory support throughout hospitalization, central line access, number of days on TPN,&#xD;
      maternal breast milk and/or formula use, gavage feeding, surgery, grade III/IV&#xD;
      intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), spontaneous intestinal&#xD;
      perforation (SIP), clinical condition and gestational age at time of any infectious&#xD;
      evaluation, description of any positive infection (cerebrospinal fluid, blood, urine,&#xD;
      pustule, abscess, osteomyelitis, endocarditis), antibiotic exposure (agent, antibiotic days),&#xD;
      length of hospital stay, discharge disposition, and MSSA/MRSA colonization screening results.&#xD;
&#xD;
      The number of MSSA/MRSA patient colonization days will be determined and compared between the&#xD;
      treatment and control groups. The proportion of persistently colonized, decolonized, and&#xD;
      recolonized study subjects at each subsequent weekly screening interval in each study group&#xD;
      will be determined and compared. The incidence and timing of MSSA/MRSA recolonization&#xD;
      following decolonization with mupirocin will be determined. The incidence of nosocomial&#xD;
      sepsis and invasive infections with any organisms will be determined and compared between the&#xD;
      two groups. The incidence of mupirocin resistance in each group will be compared. The&#xD;
      incidence of MSSA/MRSA colonization after discharge based on the outpatient screenings will&#xD;
      be compared.&#xD;
&#xD;
      An independent study monitoring committee, composed of a pharmacist and an attending&#xD;
      neonatologist (not the principal investigator), will meet after the first 30 patients are&#xD;
      enrolled and periodically after the first review to ensure the safety of this study protocol&#xD;
      for the duration of this study.&#xD;
&#xD;
      Rates of S. aureus colonization and infection during the study period will also be compared&#xD;
      with historical rates from the Crouse Hospital NICU to ensure that there was not some other&#xD;
      largely unanticipated change during the study period.&#xD;
&#xD;
      All study data will be compiled into an electronic database, which will be kept in a secure&#xD;
      password-protected computer in the principal investigator's locked office on the ninth floor&#xD;
      of Crouse Hospital. The study subjects' personal health information including name, date of&#xD;
      birth, and medical record numbers will be used to identify subjects, and their study&#xD;
      information will be part of their medical record. A copy of the data collection form and data&#xD;
      analysis form will be submitted along with this protocol and application.&#xD;
&#xD;
      STATISTICAL METHODS, DATA ANALYSIS AND INTERPRETATION&#xD;
&#xD;
      Statistical analyses will include a descriptive phase to assess the frequencies of all&#xD;
      variables and an analytic phase to evaluate the associations between methicillin-sensitivity&#xD;
      or resistance status and the patient's gestational age, gender, birth weight, discharge&#xD;
      diagnoses, discharge disposition, length of NICU stay, or presence/type of underlying&#xD;
      condition, treatments, or clinical outcomes. Pearson's X2 test will be used to compare&#xD;
      categorical variable counts/frequencies between the treatment and control groups. The&#xD;
      two-sample t-test will be used for continuous variables with normal distribution to test&#xD;
      differences between means. Appropriate alternatives, such as Wilcoxon rank sum, will be used&#xD;
      if data violate t-test assumptions. The two-proportion z-test will be used to assess&#xD;
      differences between two proportions. All hypothesis testing will be 2-tailed with a P ≤ 0.05&#xD;
      considered statistically significant. An analyst for statistical support has been involved&#xD;
      with the study design, power analysis, and sample size calculation. She will remain involved&#xD;
      throughout the study period and will assist with data analysis.&#xD;
&#xD;
      Neonatal MSSA/MRSA patient colonization days data from the Crouse Hospital NICU was used for&#xD;
      sample size calculations. Approximately 12-15 new cases of MSSA- or MRSA-colonization occur&#xD;
      each month, with a mean of 21.5 patient colonization days (standard deviation 20 days). A&#xD;
      two-sample t-test with 95% confidence interval, power of 80, and hypothesized reduction of&#xD;
      40% (8 patient colonization days), suggests a sample size of 98 patients per group, or a&#xD;
      total of approximately 200 patients in the study.&#xD;
&#xD;
      All study personnel, aside from the pharmacy staff who will randomize patients, will be&#xD;
      blinded regarding patients' study group allocation until after discharge from the Crouse&#xD;
      Hospital NICU. At time of discharge, the pharmacy will notify the principal investigator of&#xD;
      each patient's study group allocation so that data analysis by treatment group can occur.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Decolonization efficacy</measure>
    <time_frame>Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days</time_frame>
    <description>Compare the number of S. aureus patient colonization days between treatment versus control group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Trajectory of decolonization efficacy</measure>
    <time_frame>Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days</time_frame>
    <description>Compare the proportions of persistently colonized, decolonized, and recolonized study subjects at each subsequent weekly screening interval in treatment versus control group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of recolonization</measure>
    <time_frame>Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days</time_frame>
    <description>Determine the incidence and timing of recolonization with S. aureus following decolonization within the treatment group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of S. aureus infection</measure>
    <time_frame>Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days</time_frame>
    <description>Determine and compare the incidence of nosocomial invasive S. aureus infection in treatment versus control group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of mupirocin-resistance</measure>
    <time_frame>Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days</time_frame>
    <description>Determine the incidence of mupirocin-resistance in S. aureus isolates from treatment versus control group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term decolonization efficacy</measure>
    <time_frame>Within 2 months of discharge from NICU</time_frame>
    <description>Determine and compare the incidence of S. aureus colonization between 1-2 months after discharge between treatment versus control group</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">216</enrollment>
  <condition>Staphylococcus</condition>
  <arm_group>
    <arm_group_label>Mupirocin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Petroleum jelly</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mupirocin Topical Ointment</intervention_name>
    <description>Mupirocin ointment 1/2 inch ribbon applied topically to each nare and umbilicus twice daily for 5 days; repeat treatment courses possible.</description>
    <arm_group_label>Mupirocin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Petroleum Jelly</intervention_name>
    <description>Petroleum jelly ointment 1/2 inch ribbon applied topically to each nare and umbilicus twice daily for 5 days; repeat treatment courses possible.</description>
    <arm_group_label>Petroleum jelly</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants admitted to Crouse Hospital NICU with MSSA/MRSA colonization that have&#xD;
             parental consent for participation obtained within 2 days of their initial positive&#xD;
             screen.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any infant with an active or previous S. aureus infection at time of initial positive&#xD;
             S. aureus colonization screen.&#xD;
&#xD;
          -  Any infant with a condition thought to be fatal/irreversible (pulmonary hypoplasia,&#xD;
             chromosomal/genetic syndromes, fatal cardiac anomalies).&#xD;
&#xD;
          -  Any infant with a congenital condition that would prevent specimen collection or&#xD;
             treatment application (cleft lip/palate, choanal atresia, abdominal wall defects,&#xD;
             imperforate anus, etc.).&#xD;
&#xD;
          -  Sufficient length of NICU admission will be necessary to adequately measure the&#xD;
             primary outcome. Therefore, enrolled patients will only be included in data analysis&#xD;
             if they remain in the NICU until after at least one subsequent MSSA/MRSA screening is&#xD;
             performed following completion of their initial treatment course with either mupirocin&#xD;
             or placebo.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melissa U Nelson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Crouse Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Crouse Hospital - Neonatal Intensive Care Unit</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>December 18, 2020</last_update_submitted>
  <last_update_submitted_qc>December 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Crouse Hospital</investigator_affiliation>
    <investigator_full_name>Melissa Nelson</investigator_full_name>
    <investigator_title>MD, Attending Physician, Neonatologist</investigator_title>
  </responsible_party>
  <keyword>Staphylococcus aureus</keyword>
  <keyword>Staphylococcal colonization</keyword>
  <keyword>Staphylococcal infection</keyword>
  <keyword>Mupirocin</keyword>
  <keyword>Mupirocin-resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Staphylococcal Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mupirocin</mesh_term>
    <mesh_term>Petrolatum</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 13, 2021</submitted>
    <returned>October 7, 2021</returned>
  </pending_results>
  <!-- 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/NCT02967432
org study id: Crouse Hospital 2016.0125
nct id: NCT02967432
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether or not mupirocin treatment results in S.
      aureus decolonization in affected NICU patients.
This randomized controlled trial of mupirocin treatment of MSSA- and MRSA-colonized infants
      aims to determine whether or not mupirocin treatment results in S. aureus decolonization in
      affected NICU patients. MSSA- or MRSA-colonized patients who enroll in the study will be
      randomized to either a treatment group (treatment with mupirocin) or control group (treatment
      with placebo). A combination of active surveillance and targeted decolonization will
      qualitatively and quantitatively enable assessment of any changes in S. aureus colonization
      in study patients. The primary outcome measure will be the number of MSSA/MRSA patient
      colonization days in the treatment versus control groups. Secondary outcome measures will
      include the proportion of persistently colonized patients at each subsequent weekly screening
      interval in the treatment versus control group, incidence and timing of MSSA/MRSA
      recolonization in the treatment group, incidence of invasive infections with S. aureus in the
      treatment versus control group, incidence of mupirocin-resistance in treatment versus control
      group, and incidence of MSSA/MRSA colonization after NICU discharge in the treatment versus
      control group.

      STUDY PROCEDURES

      Current standard of care in the NICU includes active universal screening of all admitted
      patients weekly for MSSA/MRSA colonization and contact precautions for MRSA-positive
      patients. No universal or targeted decolonization procedures are currently utilized. NICU
      patients who screen positive for MSSA/MRSA colonization will be approached for participation
      in this study and consent will be obtained from a parent within 2 days of the initial
      positive screening result by a neonatologist. At time of enrollment, patients will be
      randomized to either the treatment or control group. The pharmacy team will assign
      randomization; all NICU staff will be blinded to the patient's study group assignments
      throughout their admission. The treatment group will receive mupirocin ointment applied twice
      daily inside the nares and to the skin around the umbilicus for five days. The control group
      will receive a placebo ointment (petroleum jelly) applied in an identical fashion. The
      control group will not receive mupirocin ointment at any time, regardless of colonization
      status. If patients have recurrent positive MSSA/MRSA screens during the study, they may
      receive additional identical courses of treatment with either mupirocin or placebo based on
      their study group assignment.

      The mupirocin and placebo petroleum jelly ointments will be supplied by the Crouse Hospital
      pharmacy and sent to the NICU daily for twice daily application by the nursing staff. Both
      groups will receive a ½ inch ribbon topical application of mupirocin or petroleum jelly
      ointment according to their assignment around the umbilicus and a ½ inch ribbon inside each
      nare. The neonatal nursing staff will receive appropriate education regarding the application
      technique and study protocol prior to study initiation. The cost of the mupirocin and placebo
      ointments will be paid for by Neonatal Associates of Central New York, LLC, and patients will
      not receive any fee for this service.

      Colonization with MSSA/MRSA will be screened weekly on Mondays, in line with current Crouse
      Hospital NICU standard of care. MSSA/MRSA screening is performed by polymerase chain reaction
      (PCR). Sample collection involves swabbing an infant's nares, umbilicus, and groin with a
      cotton-tipped applicator. The swab tip is then sent to the Crouse Hospital Laboratory for
      Staphylococcus species identification. There will be no additional costs associated with
      these screenings, as this is already standard of care. Mupirocin resistance will be assessed
      by disk diffusion assay with E-test methodology to determine MICs. The costs associated with
      this additional test will be paid for by Neonatal Associates of Central New York, LLC, and
      patients will not receive any fee for this service. An additional MSSA/MRSA screen will be
      performed approximately 2 months after discharge at a patient's primary care physicians'
      office visit. Sample collection procedures will be identical to the screens performed at
      Crouse, and the screens will be sent to Laboratory Alliance of Central New York's
      Microbiology Department for testing. Results will be made available to the principal
      investigator. The costs associated with this additional outpatient screening test will be
      paid for by Neonatal Associates of Central New York, LLC, and patients will not receive any
      fee for this service.

      Routine Crouse Hospital NICU policies regarding the use of contact precautions for any MRSA
      colonized infant will continue during the study period. If an infant enrolled in the study
      displays signs or symptoms concerning for infection, diagnostic evaluation and treatment will
      be guided by the attending neonatologist, not deviating from the current NICU standard of
      care. Parents are notified if their infant screens positive for MRSA colonization and if any
      diagnostic evaluation was performed on their infant. Current standards of infection
      prevention, such as aggressive and consistent hand hygiene, sterile procedure policies, etc.
      will be continued during this study.

      Baseline patient demographics and clinical characteristics and outcomes will be collected on
      every study subject, including: birth weight, sex, gestational age, birth hospital, mode of
      delivery, maternal age, length of rupture of membranes, chorioamnionitis, documented maternal
      MRSA history when available, maternal antibiotic exposure, maternal drug abuse history,
      respiratory support throughout hospitalization, central line access, number of days on TPN,
      maternal breast milk and/or formula use, gavage feeding, surgery, grade III/IV
      intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), spontaneous intestinal
      perforation (SIP), clinical condition and gestational age at time of any infectious
      evaluation, description of any positive infection (cerebrospinal fluid, blood, urine,
      pustule, abscess, osteomyelitis, endocarditis), antibiotic exposure (agent, antibiotic days),
      length of hospital stay, discharge disposition, and MSSA/MRSA colonization screening results.

      The number of MSSA/MRSA patient colonization days will be determined and compared between the
      treatment and control groups. The proportion of persistently colonized, decolonized, and
      recolonized study subjects at each subsequent weekly screening interval in each study group
      will be determined and compared. The incidence and timing of MSSA/MRSA recolonization
      following decolonization with mupirocin will be determined. The incidence of nosocomial
      sepsis and invasive infections with any organisms will be determined and compared between the
      two groups. The incidence of mupirocin resistance in each group will be compared. The
      incidence of MSSA/MRSA colonization after discharge based on the outpatient screenings will
      be compared.

      An independent study monitoring committee, composed of a pharmacist and an attending
      neonatologist (not the principal investigator), will meet after the first 30 patients are
      enrolled and periodically after the first review to ensure the safety of this study protocol
      for the duration of this study.

      Rates of S. aureus colonization and infection during the study period will also be compared
      with historical rates from the Crouse Hospital NICU to ensure that there was not some other
      largely unanticipated change during the study period.

      All study data will be compiled into an electronic database, which will be kept in a secure
      password-protected computer in the principal investigator's locked office on the ninth floor
      of Crouse Hospital. The study subjects' personal health information including name, date of
      birth, and medical record numbers will be used to identify subjects, and their study
      information will be part of their medical record. A copy of the data collection form and data
      analysis form will be submitted along with this protocol and application.

      STATISTICAL METHODS, DATA ANALYSIS AND INTERPRETATION

      Statistical analyses will include a descriptive phase to assess the frequencies of all
      variables and an analytic phase to evaluate the associations between methicillin-sensitivity
      or resistance status and the patient's gestational age, gender, birth weight, discharge
      diagnoses, discharge disposition, length of NICU stay, or presence/type of underlying
      condition, treatments, or clinical outcomes. Pearson's X2 test will be used to compare
      categorical variable counts/frequencies between the treatment and control groups. The
      two-sample t-test will be used for continuous variables with normal distribution to test
      differences between means. Appropriate alternatives, such as Wilcoxon rank sum, will be used
      if data violate t-test assumptions. The two-proportion z-test will be used to assess
      differences between two proportions. All hypothesis testing will be 2-tailed with a P ≤ 0.05
      considered statistically significant. An analyst for statistical support has been involved
      with the study design, power analysis, and sample size calculation. She will remain involved
      throughout the study period and will assist with data analysis.

      Neonatal MSSA/MRSA patient colonization days data from the Crouse Hospital NICU was used for
      sample size calculations. Approximately 12-15 new cases of MSSA- or MRSA-colonization occur
      each month, with a mean of 21.5 patient colonization days (standard deviation 20 days). A
      two-sample t-test with 95% confidence interval, power of 80, and hypothesized reduction of
      40% (8 patient colonization days), suggests a sample size of 98 patients per group, or a
      total of approximately 200 patients in the study.

      All study personnel, aside from the pharmacy staff who will randomize patients, will be
      blinded regarding patients' study group allocation until after discharge from the Crouse
      Hospital NICU. At time of discharge, the pharmacy will notify the principal investigator of
      each patient's study group allocation so that data analysis by treatment group can occur.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Decolonization efficacy
time frame: Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days
description: Compare the number of S. aureus patient colonization days between treatment versus control group
measure: Trajectory of decolonization efficacy
time frame: Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days
description: Compare the proportions of persistently colonized, decolonized, and recolonized study subjects at each subsequent weekly screening interval in treatment versus control group
measure: Incidence of recolonization
time frame: Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days
description: Determine the incidence and timing of recolonization with S. aureus following decolonization within the treatment group
measure: Incidence of S. aureus infection
time frame: Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days
description: Determine and compare the incidence of nosocomial invasive S. aureus infection in treatment versus control group
measure: Incidence of mupirocin-resistance
time frame: Remaining length of NICU admission status post positive screening culture, approximately between 7 to 365 days
description: Determine the incidence of mupirocin-resistance in S. aureus isolates from treatment versus control group
measure: Long-term decolonization efficacy
time frame: Within 2 months of discharge from NICU
description: Determine and compare the incidence of S. aureus colonization between 1-2 months after discharge between treatment versus control group
arm group label: Mupirocin
arm group type: Experimental
arm group label: Petroleum jelly
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Mupirocin Topical Ointment
description: Mupirocin ointment 1/2 inch ribbon applied topically to each nare and umbilicus twice daily for 5 days; repeat treatment courses possible.
arm group label: Mupirocin
intervention type: Drug
intervention name: Petroleum Jelly
description: Petroleum jelly ointment 1/2 inch ribbon applied topically to each nare and umbilicus twice daily for 5 days; repeat treatment courses possible.
arm group label: Petroleum jelly
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Melissa U Nelson, MD
role: Principal Investigator
affiliation: Crouse Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Crouse Hospital
investigator full name: Melissa Nelson
investigator title: MD, Attending Physician, Neonatologist
mesh term: Staphylococcal Infections
mesh term: Mupirocin
mesh term: Petrolatum
sharing ipd: No
submitted: September 13, 2021
returned: October 7, 2021