Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02967432 |
| Other study ID # |
Crouse Hospital 2016.0125 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
October 2016 |
| Est. completion date |
December 2019 |
Study information
| Verified date |
December 2020 |
| Source |
Crouse Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to determine whether or not mupirocin treatment results in S.
aureus decolonization in affected NICU patients.
Description:
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.
