Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02537964 |
| Other study ID # |
0018-15-SZMC |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 2016 |
| Est. completion date |
October 1, 2020 |
Study information
| Verified date |
October 2020 |
| Source |
Shaare Zedek Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a prospective, controlled; crossover study of daily bathing with no-rinse, 2%
chlorhexidine gluconate (CHG) impregnated washcloths versus bathing with water/soap or water
according to gestational age and weight (e.g. standard bathing). The trial will take place in
the Neonatal intensive care unit (NICU).
Baseline data ragarding bloodstream infections (BSI) and colonization with multidrug
resistant orgnisms (MDRO) will be collected for 3-6 months prior to patient enrollment. In
the preliminary phase of the study we will establish the safety of chlorhexidine bathing
using Clinell ® Chlorhexidine wash cloths on three groups of patients: term infants admitted
to the NICU; late preterm infants (34-37 weeks); preterm infants 30-34 weeks of gestation.
Interim analysis for adverse events will be performed after each group of patients.
In the subsequent phases of the study, all infants admitted to the NICU and enrolled in the
study will be bathed three times a week with Chlorhexidine wash cloths during the initial
6-months study period (intervention), followed by standard bathing during the second 6-months
period, then again intervention period for 6 months and standard bathing for 6-months. Total
study period- 3 years.
Data collection will include all bloodstream infections as well as surveillance cultures
Description:
The study will take place in the Neonatal intensive care unit (NICU) of Shaare-Zedek Medical
Center
Baseline data ragarding bloodstream infections (BSI) and colonization with multidrug
resistant orgnisms (MDRO) will be collected for 3-6 months prior to patient enrollment.
Preliminary study:
In order to establish safety , we will enroll infants admitted to the NICU to three
successive treatment groups , as follows: the first group will include term infants admitted
to the NICU (gestational age 37+6 and >7 days old), the second group will include near-term
infants (gestational age > 34+0 to 36+6 weeks and >7 days old) and the third group will
include premature infants (gestational age >30+0 to 33+6 and >=10 days old). We intend to
enroll up to 20 patients in each group, for a minimum of 200 patient days per group . All
infants will be assigned for bathing three times a week with washcloths impregnated with 2%
chlorhexidine gluconate (Clinell ® Chlorhexidine wash cloths, GAMA healthcare) for the
duration of their NICU stay. The infant's skin will be monitored continuously as described
below . In case of grade 3 or 4 reactions, the study interventions will be temporarily
suspended, and the adverse event will be reported to the Helsinky committee and to the study
steering committee. If no grade 3 or 4 reactions will be encountered after at least 200
patient days per group, enrollment to the subsequent group will be performed (e.g if no grade
3-4 reaction will be encountered for 200 patient days in group 1, we will start enrolling
patients for group 2 etc.). If no grade 3-4 dermatitis is encountered in the preliminary
study, we will initiate enrollment as described below.
In the subsequent phases of the study, :
All infants in the NICU eligible for the study will be assigned for bathing three times a
week with washcloths impregnated with 2% chlorhexidine gluconate (Clinell ® Chlorhexidine
wash cloths, GAMA healthcare) during the initial 6-months study period (intervention),
followed by standard bathing during the second 6-months period, then again intervention
period for 6 months and standard bathing for 6-months. Total study period- 2.5 years.
Inclusion criteria: infants weighing ≥1500 grams and >=10 days of age ; parents' informed
consent Exclusion criteria: infants weighing <1500 grams or <10 days of age; parents' refusal
to sign informed consent.
For standard bathing procedure see appendix 1.
Before the study initiation, as well as at the beginning of each study period, nurses will be
instructed on the proper technique for bathing patients. Bathing will be performed according
to product brochure, three times a week.
Outcome measures
A. Number of bacteremia episodes per 1000 patient days during the intervention periods
compared with the control periods.
B. Number of new patients colonized with methicillin resistant Staphylococcus aureus (MRSA),
vancomycin resitant enterococcus (VRE), carbapenem resistant Acinetobacter baumanii (CRAB) or
extended spectrum beta-lactamase (ESBL) producing organisms per total number of patients,
monthly range and variance.
C. Number of new patients colonized with MRSA, VRE, CRAB or ESBL per 1000 eligible patient
days [ Total patient days - total patient days for patients identified with multidrug
resistant organisms (MDRO)]
D. Time to colonization with MDRO during the intervention periods compared with the control
periods.
Data collection:
Each patient admitted to the NICU during the study periods and meeting the inclusion
criteria, will be recorded and assigned a specific study number. The dates of admission and
dates of discharge will be recorded and used to calculate length of stay and to determine the
incidence of nosocomial infections based on microbiological data. Clinical and laboratory
data, including the use of invasive device (intravascular devices, mechanical ventilation,
feeding tubes) will be collected on standardized forms. The data will be coded under a
password protected database and linked only to study patient identifier.
Infections and MDRO acquisitions will be monitored during the study period. Events occurring
within 2 days after the transition will be assigned to the previous bathing period.
For infection surveillance, daily review of cultures and new orders for antibiotic therapy
will be performed for all study participants. Infectious events will be evaluated by an
independent investigator blinded to the intervention period.
Active surveillance testing for MDRO will be performed once every two weeks during the study
period. Swabs from the nasopharynx (for MRSA)] and from the rectal area (for ESBL producing
organisms, VRE and CRAB) will be obtained by unit staff and processed in the microbiology
laboratory of Shaare-Zedek Medical Center.
Trial oversight:
The steering committee of the study will include, except for the PI, an Infectious Disease
physician and a neonatologist . There will be biweekly discussions of the progress report,
reporting of compliance with active surveillance, reporting of compliance with bathing, and
any adverse reactions or other problems.
Statistical analyses
Changes in the rates of BSI and clinical sepsis will be compared between the intervention and
the control period. Continuous variables will be examined with the use of two-sample t-tests
and linear regression modeling, and categorical variables will be examined by means of
Fisher's exact test. Cox proportional-hazards regression model will be used to compare the
time from admission until the first primary bloodstream infection , clinical sepsis or
acquisition of MDRO between the control and intervention periods.
Sample size calculation: based on our ongoing surveillance, there are 2-3 BSI events per 1000
patients -days in our NICU. In order to detect a 50% reduction in BSI rates , the
investigators will need 37,096 patient days (18,548 in each group) in order to have 80% power
to reject the null hypothesis, with 0.05 level of significance. Currently, our average annual
census is 45,000 patient days. therefore, a 2-year study will have >80% power to reject the
null hypothesis (the BSI rates in the control period equal the rates in the intervention
period).
Safety and monitoring.
A study that evaluated the tolerability of 2% CHG for catheter insertion antisepsis among
infants ≥1500 grams and ≥7 days old found no significant dermatitis reactions . Seven of 48
infants had measurable CHG levels in the blood. In a trial that evaluated a multifactorial
approach to reduce the rates of CLABSI, Andersen et al. noted that 4 of 36 neonates <1000g
developed contact dermatitis after a 2% CHG scrub. There were no episodes of contact
dermatitis in 49 study participants who were ≥1000g . The alternative for antisepsis in
neonates is povidone-iodine. However, iodine absorption that may compromise thyroid function
is one reason to explore the use of CHG. Although CHG was reported to be absorbed through
neonatal skin in several trials, no significant systemic side effects were reported ' .
Animal trials showed no significant toxicity from CHG . The US Food and Drug Administration
(FDA) states on the drug facts box of 2% CHG cloth:" use with care in premature infants or
infants under 2 months of age. These products may cause irritation or chemical burns".
Each participant's skin will be examined daily by nursing staff and twice a week by study
personnel.
Skin reactions will be graded and recorded on a standard report form (appendix 2).
Grade 3 and 4 skin reactions will be reported as serious adverse events.
