Community Central Line Infection Prevention Trial
Condition: Infection
MeSH terms: Infections; Communicable Diseases
Study type: Interventional

Summary: 
      The overall goal of this Community Central Line Infection Prevention (CCLIP) trial, supported
      by grant R01 HS022870 from the Agency for Healthcare Research and Quality, is to determine
      whether use of a promising new intervention, namely 70% isopropyl alcohol embedded protective
      caps on central lines, in the home setting is associated with a reduction in ambulatory
      central line-associated bloodstream infections (CLABSI) in a high-risk population of
      pediatric hematology/oncology patients. Despite successes in CLABSI reduction efforts for
      inpatients, it remains unknown what generalizable best practices should be with chronic
      central lines in the home setting and how effective involving patients and caregivers across
      multiple institutions in CLABSI reduction efforts will be. This research will involve a
      cluster-randomized, cross-over design, clinical trial. This proposal will focus on the
      caregivers integral to ambulatory pediatric central line care: patients and families. The
      specific aims of the proposed research program are:

      Specific Aim #1: Evaluate whether use of 70% isopropyl alcohol embedded protective caps on
      central lines reduces the rate of CLABSI in ambulatory pediatric hematology/oncology
      patients.

      Hypothesis: Use of 70% isopropyl alcohol embedded protective caps on central lines will be
      associated with at least a 25% reduction in the ambulatory CLABSI rate for pediatric
      hematology/oncology patients.

      Specific Aim #2: Evaluate whether use of 70% isopropyl alcohol embedded protective caps on
      central lines reduces the rate of all positive blood cultures in ambulatory pediatric
      hematology/oncology patients.

      Hypothesis: Use of 70% isopropyl alcohol embedded protective caps on central lines will be
      associated with at least a 25% reduction in the positive blood culture rate at home for
      pediatric hematology/oncology patients.

      Specific Aim #3: Evaluate whether the use of 70% isopropyl alcohol embedded protective caps
      on central lines changes the distribution of bacteria isolated from blood cultures of
      pediatric hematology/oncology patients.

      Hypothesis: Use of 70% isopropyl alcohol embedded protective caps on central lines will
      reduce Gram-positive CLABSI, secondary blood steam infections, and single positive blood
      cultures at home for pediatric hematology/oncology patients.
    

Detailed description: 
      Study Design and Population: The proposed study will use a cluster-randomized, 2 period
      crossover design, clinical trial to evaluate a promising new intervention, namely 70%
      isopropyl alcohol embedded protective caps, to reduce CLABSIs, 2ndry BSI, and SPBC at home
      for chronic central lines in pediatric hematology/oncology patients. The Control Arm will
      involve "usual care" for ambulatory central lines per institutional policy and the
      Intervention Arm will add use of 70% isopropyl alcohol embedded protective caps to "usual
      care. Each participating institution will be randomly assigned to either the intervention or
      control phase of the design for the first 12 months of the study. There will then be a 3
      month wash out period, followed by each institution then implementing either the control or
      intervention phase for another 12 months such that each institution will complete 12 months
      each in the intervention arm and the control arms of the study.

      Sixteen pediatric hematology/oncology institutions will serve as the core population for this
      proposal and unit of randomization. All ambulatory patients taken care of by these pediatric
      hematology/oncology clinics at these institutions will be eligible for this study. The only
      inclusion criteria will be presence of an external central line. Given the intervention is a
      protective cap for central line access ports, patients who only have a totally implanted port
      as their central venous access will not be eligible for this study as the intervention is not
      physically applicable to such central lines.

      The intervention the investigators will deploy is the CUROS® brand of 70% isopropyl alcohol
      embedded protective caps for central lines. These caps are manufactured by Ivera Medical
      Corporation. As in kind contribution to this proposed study, Ivera Medical Corporation has
      agreed to donate and distribute all needed CUROS® caps to the participating institutions for
      the duration of this study. If any of the participating teams wishes to instead use a
      comparable brand of 70% isopropyl alcohol embedded protective caps for central lines that
      will be permitted.

      Distribution of the CUROS® caps will be accomplished within the clinics of each participating
      institution and compliance with the intervention at homes will be monitored by clinic staff
      via tracking counts of CUROS® caps dispensed to families. Children with chronic
      hematologic/oncologic conditions are seen frequently in clinic, often up to every week.
      Clinic staff can distribute and track volume of CUROS® caps dispensed to each family/patient,
      with the family/patient can report back each visit on the volume of CUROS® caps utilized.
      This will ensure reliable distribution to the families/patients, provide a face to face
      educational opportunity to ensure proper application of the CUROS® cap, and provide
      compliance opportunities via counts of CUROS® caps utilized.

      This proposal will involve a cluster-randomized, 2 period crossover design, clinical trial.
      Given this proposal's focus on reducing central line infections at home, the main
      facilitators of best practice use of these caps at home will be the families and patients
      themselves. The research team will spread the needed additional education, tools, data,
      analyses, and support for this proposal.

      Study Organization and Timeline: The work will build on the partnership between the pediatric
      quality improvement research group at Johns Hopkins University and the vendor Ivera Medical
      Corporation, maker of the CUROS® brand 70% isopropyl alcohol embedded protective caps for
      central lines. Dr. Miller is Principal Investigator and serves as Vice Chair of Quality and
      Safety, Director of Division of Quality and Safety at the Johns Hopkins Children's Center.
      Dr. Miller had led and continues to lead efforts to transform the quality and safety of the
      delivery system at Johns Hopkins University and is a formally trained in Lean Six Sigma
      quality improvement as well as having her Masters of Science degree in clinical research. In
      addition, Dr. Aaron Milstone at Johns Hopkins University, director of pediatric hospital
      epidemiology and infection control and an accomplished researcher in pediatric infection
      prevention, will be a Co-Investigator on this proposal. Dr. Milstone led the recently
      published clinical trial work in Lancet describing the impact of chlorhexidine bathing on
      CLABSI and positive blood cultures in children in 10 PICUs. Dr. Elizabeth Colantuoni is a
      Biostatistician and Assistant Scientist in the Johns Hopkins Bloomberg School of Public
      Health.

      The work will span four years. Year 1 Preparatory work will include establishing
      Institutional Review Board approval at each of the participating institutions, setting up
      data collection and submission processes, setting up distribution mechanisms for the
      intervention both to the clinics and then within each clinic to the homes, and educating
      providers, patients, and families on how to apply the CUROS® cap across all the participating
      institutions. Years 2, 3, and 4 will include two 12 month trial periods with a 3 month wash
      out period in between. The last 9 months of Year 4 will be used for data analysis and
      manuscript preparation.

      Methods SPECIFIC AIM 1 and SPECIFIC AIM 2:

      Specific Aim #1: Evaluate whether use of 70% isopropyl alcohol embedded protective caps on
      central lines reduces the rate of CLABSI in ambulatory pediatric hematology/oncology
      patients.

      Hypothesis: Use of 70% isopropyl alcohol embedded protective caps on central lines will be
      associated with at least a 25% reduction in the ambulatory CLABSI rate for pediatric
      hematology/oncology patients.

      Specific Aim #2: Evaluate whether use of 70% isopropyl alcohol embedded protective caps on
      central lines reduces the rate of all positive blood cultures in ambulatory pediatric
      hematology/oncology patients.

      Hypothesis: Use of 70% isopropyl alcohol embedded protective caps on central lines will be
      associated with at least a 25% reduction in the positive blood culture rate at home for
      pediatric hematology/oncology patients.

      Independent variables: The primary independent variable will be ambulatory CLABSI rates for
      Specific Aim #1 and all positive blood culture rates, defined as CLABSI rate + MBI-CLABSI
      rates + Secondary BSI rates + single positive blood culture (SPBC) rates, for Specific Aim
      #2. All of the participating units already devote Hospital Infection Control staff to
      identify and track all 3 of these types of ambulatory central line infections.

      Dependent variable: The dependent variable for these Specific Aims will be the dichotomous
      assignment to either control or intervention arms where unit will receive both arms.

      Data collection method: All Hematology/Oncology units will submit monthly aggregate clinic
      data on CLABSI, MBI-CLABSI, Secondary BSI and SPBC (numerators and denominators) via a
      web-based data entry tool.

      Exploratory analyses: Events and line-days at the unit level will be calculated to summarize
      rates of infections (CLABSI and all infections) by treatment and period as well as by month
      to assess for any important trends. These trends will be evaluated using scatterplots and
      line plots, overall and separately by treatment arm and period. Summary statistics, such as
      mean, median, interquartile range and variance, for the monthly number of infection events
      and rates will be calculated for the overall sample and by treatment and period. In case
      missing data occurs in our analysis we will explore the relationship between missing data and
      the unit's observed data in months prior and our analysis methods will be valid under the
      assumptions that the missing data are generated completely at random or depend on the prior
      observed rates (missing at random). Our data integrity efforts and frequent contacts with
      this team will work to minimize any instances of missing data.

      Multivariate analyses: Random effects Poisson regression models will be used to test for a
      treatment effect. Specifically, the monthly number of CLABSI (Specific Aim #1) or the monthly
      number of all infections (Specific Aim #2) will be modeled as a function of the dichotomous
      treatment assignment and an indicator for when the treatment arm was received (first or
      second 12 month period) with inclusion of an offset representing the monthly number of
      central line days and a random intercept for unit to account for the correlation of monthly
      rates of infections over time within the same unit. The models rely on two key assumptions:
      i) the infection rates follow a Poisson distribution where the mean rate is the same as the
      variance in the rate and ii) the correlation of the rates within a unit over time is
      exchangeable. These assumptions will be assessed via descriptive analyses and by adding a
      robust variance estimate clustering on the unit.

      Methods, Specific Aim #3: To evaluate whether the use of 70% isopropyl alcohol embedded
      protective caps on central lines changes the distribution of bacteria isolated from blood
      cultures of ambulatory pediatric hematology/oncology patients.

      Hypothesis: Use of 70% isopropyl alcohol embedded protective caps on central lines will be
      associated with altered microbial epidemiology for CLABSI, secondary blood steam infections,
      and single positive blood cultures at home for pediatric hematology/oncology patients.

      Independent variables: Organisms isolated for all blood cultures (CLABSI + MBI-CLABSI +
      Secondary BSI + SPBC) in patients involved in this study will be collected from participating
      teams during both the Control and Intervention arms of the clinical trial and sorted into
      Gram Positive versus Gram Negative organisms.

      Dependent variable: The dependent variable for this Specific Aim will be the dichotomous
      assignment to either control or intervention arms.

      Data collection method: All Hematology/Oncology ambulatory care teams will submit the
      microbial pattern data for all positive blood cultures.

      Analyses: The analysis would be a comparison of proportions of Gram positive organisms
      causing CLABSI, SPBC, and all positive blood cultures between the control and intervention
      study arms. Given that Gram positive organisms are the most common organisms causing CLABSI
      and SPBC in children, achieving a reduction in Gram positive organisms would be an important
      additional finding of this clinical trial.
    

Intervention name(s): 70% Isopropyl alcohol embedded caps; Usual Care
Intervention type(s): Device; Other
Intervention description(s): Protective cap on central lines; This involves the Best Practice Central Line Maintenance Care Bundle which includes;
Daily assessment whether central line is needed
Central line Site Care
Central line Hub/Cap/Tubing Care
Other intervention name(s): Curos Cap by Ivera Medical Corporation
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Pediatrics; Medical Oncology; Catheters; Infection