Parafilm Application to Prevent Central Line Associated Bloodstream Infections in Pediatric Patients Undergoing Hematopoietic Cell Transplantation
Phase: NA
Conditions: Central Line Associated Bloodstream Infections (CLABSI), Bone Marrow Transplant
Sponsor: Emory University

Parafilm Application to Prevent Central Line Associated Bloodstream Infections 
in Pediatric Patients Undergoing Hematopoietic Cell Transplantation 
Protocol version date: October 24, 2018 
NCT02575079 
 
Parafilm protocol v3 (10-24-18)                                                                                                                                     1 
 

Parafilm Application to Prevent Central Line Associated Bloodstream Infections in 
Pediatric Patients Undergoing Hematopoietic Cell Transplantation 
 
Principal Investigators 
Lakshmanan Krishnamurti, MD 
Elizabeth Stenger, MD (Adjunct faculty) 
 
 
Co-Investigators 
Lea Kendrick, LPN 
Leigh McManus, RN MSN 
Joanna Newton, MD 
Caroline Rooke, BSN CPHON 
 
 
 
Parafilm protocol v3 (10-24-18)                                                                                                                                     2 
 

TABLE OF CONTENTS 
  
SECTION  
 
 
 
 
 
 
 
 
 
 
PAGE  
 
ABSTRACT   
 
 
 
 
 
 
 
 
 
4  
 
 
 
 
 
 
 
1. GOALS AND OBJECTIVES (SCIENTIFIC AIMS) 
 
 
 
 
5 
1.1.  Primary  
 
 
 
 
 
 
 
 
 
5  
1.2.  Secondary   
 
 
 
 
 
 
 
 
5 
  
2. BACKGROUND   
 
 
 
 
 
 
 
 
5 
  
3. SUMMARY OF TRIAL TO DATE AND OVERVIEW OF MODIFICATIONS TO  
6  
      PROTOCOL 
 
4. RESEARCH DESIGN AND METHODS  
 
 
  
 
 
7  
4.1. Study Design  
 
 
 
 
 
 
 
 
7 
4.2. Study Enrollment  
 
 
 
 
 
 
 
 
7  
4.3. Eligibility Criteria  
 
 
 
 
 
 
 
 
7 
  
5. TREATMENT PLAN  
 
 
 
 
 
 
 
 
8 
5.1.  Overview 
 
 
 
 
 
 
 
 
 
8 
5.2.  Concomitant Treatment Restrictions 
 
 
 
 
 
8 
5.3.  Schedule for Parafilm 
 
 
 
 
 
 
 
8 
5.4.  Positive Blood Culture 
 
 
 
 
 
 
 
9 
 
6. AGENT INFORMATION   
 
 
 
 
 
 
 
9  
 
7. EVALUATIONS 
 
 
 
 
 
 
 
 
 
9 
 
8. CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY  
CRITERIA  
 
 
 
 
 
 
 
 
 
10 
 
8.1.  Criteria for Removal from Protocol Therapy  
 
 
 
 
10 
8.2.  Off Study Criteria  
 
 
 
 
 
 
 
 
10 
 
9.  STATISTICAL CONSIDERATIONS  
 
 
 
 
 
 
11 
9.1.  Statistical Design  
 
 
 
 
 
 
 
 
11 
9.2.  Patient Accrual and Expected Duration of Trial  
 
 
 
 
11 
9.3.  Statistical Analysis Methods  
 
 
 
 
 
 
11 
 
10.  ADVERSE EVENT REPORTING 
 
 
 
 
 
 
13 
10.1. 
Common Toxicity Criteria for Adverse Events 
 
 
 
13 
10.2. 
Reporting Requirements 
 
 
 
 
 
 
13 
 
11.  CENTRAL LINE ASSOCIATED BLOODSTREAM INFECTION (CLABSI) 
 
13 
11.1. 
CDC Criteria for CLABSI 
 
 
 
 
 
 
13 
11.2. 
BSI Committee 
 
 
 
 
 
 
 
14 
 
APPENDIX I: CVL Dressing Changes, Including PICCs 
 
 
 
 
15 
 
APPENDIX II: Protocol for the Management of Intravascular Devices 
 
 
18 
Parafilm protocol v3 (10-24-18)                                                                                                                                     3 
 

 
APPENDIX III: CVL Access: Blood Draws and Medication Administration  
 
26 
 
APPENDIX IV: Venous Line Flushing 
 
 
 
 
 
 
30 
 
REFERENCES  
 
 
 
 
 
 
 
 
 
32 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parafilm protocol v3 (10-24-18)                                                                                                                                     4 
 

ABSTRACT 
 
Central line associated bloodstream infections (CLABSI) result in significant morbidity and 
mortality, particularly in patients undergoing hematopoietic cell transplantation (HCT). HCT 
patients are at high risk for CLABSI due to multiple factors, including prolonged immune 
suppression and the need for long-term central venous access. Data in pediatric HCT patients is 
sparse and previous and current investigations have utilized interventions that may have 
downstream effects on bacterial flora and antibiotic resistance patterns. Parafilm is a plastic film 
made of paraffin that is primarily utilized to seal and/or protect containers in laboratories. Based 
upon its unique properties, parafilm was studied in a small series of TPN-dependent pediatric 
patients with short-gut syndrome. When applied as a protective barrier at the end of central lines, 
parafilm significantly reduced the incidence of CLABSI in this patient population. This non-
randomized pilot quality improvement initiative will extend the use of a parafilm central line barrier 
as standard of care to pediatric HCT patients. The primary aims of this study are to determine the 
feasibility of this intervention and to reduce the incidence of CLABSI in pediatric HCT patients. 
The secondary aims of this study are to further characterize factors that impact the CLABSI rate 
and to evaluate patient, caregiver, and healthcare provider perception of this intervention. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. GOALS AND OBJECTIVES (SCIENTIFIC AIMS) 
Parafilm protocol v3 (10-24-18)                                                                                                                                     5 
 

 
1.1. Primary 
 
1.1.1. To determine the feasibility of applying and maintaining parafilm as a protective 
barrier to the central lines of pediatric hematopoietic stem cell transplant (HCT) inpatients 
and outpatients in order to prevent central line associated bloodstream infections 
(CLABSI).  
 
1.1.2. To determine if parafilm application reduces the rate of CLABSI in pediatric patients 
undergoing HCT. 
 
1.2. Secondary 
 
1.2.1. To characterize the pre- and post-HCT characteristics which impact the rate of 
CLABSI in pediatric patients undergoing HCT. 
 
1.2.2. To evaluate patient and caregiver (family and healthcare provider) perception of the 
effectiveness of parafilm, including ease of use, ease of maintenance, and ability to 
prevent infection. 
 
2. BACKGROUND 
 
CLABSI are an important subset of hospital-acquired infections (HAI) that lead to significant 
morbidity and mortality.  The Centers for Disease Control and Prevention (CDC) estimates 
that 31,000 CLABSI occurred in U.S. hospitals in 2009, and that each episode carries mortality 
of 15-25% and excess costs of $16,550.1  Due to this significant burden, the Centers for 
Medicare and Medicaid Services (CMS) decreased reimbursement for CLABSI in October 
2008 and mandated that all acute care hospitals begin reporting CLABSI data to the CDC’s 
National Healthcare Safety Network (NHSN) in January 2011.   
 
Patients undergoing HCT are at particularly high risk for CLABSI due to need for longer term 
central venous access, prolonged period of neutropenia, breakdown of mucosal barriers (e.g. 
mucositis), and, in allogeneic HCT, the need for post-transplant immune suppression.  
Previous studies of pediatric and adult HCT patients report a 21-49% incidence for bacteremia 
and 17-36% for CLABSI.2-6  A recent report in pediatric HCT patients was strengthened by the 
number of patients (n=319), the prospective study design, the inclusion of both ambulatory 
and inpatient data, and the use of current CLABSI nomenclature, although this study 
combined pediatric HCT and oncology patients.7  They report 0.65 ambulatory CLABSI and 
2.2 inpatient CLABSI, both per 1000 central line days, which is comparable to the 2011 NHSN 
report of 2.2 inpatient CLABSI per 1000 central line days in pediatric HCT (mean; 13 
centers).7,8   
 
Lukenbill et al9 recently differentiated between standard definition CLABSI and “modified 
CLABSI,” which excluded pathogens associated with mucosal breakdown, although this 
report was only in young adult and adult patients undergoing HCT for myelodysplastic 
syndrome and acute myeloid leukemia.9  This distinction is important as the 2014 CDC 
guidelines subdifferentiate mucosal barrier injury laboratory-confirmed bloodstream infections 
(MBI-LCBI) from CLABSI.  MBI-LCBI include bloodstream infections with intestinal organisms 
or viridans group streptococci in patients who are neutropenic or who have undergone HCT 
within the prior year and currently complicated by grade III-IV graft-versus-host disease 
(GVHD).  While this subgroup of CLABSI is currently only being utilized for reporting purposes, 
Parafilm protocol v3 (10-24-18)                                                                                                                                     6 
 

it is possible that certain subgroups of CLABSI (such as MBI-LCBI) may be viewed differently 
in the future with differential CMS reimbursement (as opposed to current non-reimbursement 
for all CLABSI). 
  
The collection and reporting of CLABSI data has allowed quantification of the burden, but 
most importantly, it allows for implementation of interventions to decrease CLABSI.  Simple 
interventions, such as the use of central line maintenance bundles to improve compliance with 
evidence-based practices, have decreased CLABSI in pediatric ICU patients and shown 
promise in pediatric oncology.10,11  The electronic medical record can also be used to improve 
bundle compliance.10  In pediatric HCT patients, training of medical staff and patient 
caregivers in best practice central line care has been shown to decrease CLABSI.12   
 
Therapies to prevent CLABSI are also being investigated.  The use of quinolone antibiotics 
has been shown to decrease the incidence of CLABSI in pediatric HCT patients,3 and the use 
of levofloxacin is currently being investigated in a randomized fashion in pediatric patients 
with acute leukemia or undergoing HCT by the Children’s Oncology Group (COG) (NCT 
01371656).   In another ongoing trial, the COG is comparing the use of standard central line 
cleansing to cleansing with chlorhexidine gluconate (CHG; NCT01817075).  While these 
interventions hold promise in decreasing the incidence of CLABSI, both levofloxacin and CHG 
may alter bacterial flora and/or bacterial drug resistance; as such, both COG studies will be 
investigating these as secondary outcomes. 
 
Parafilm is a plastic film made of paraffin (Sigma-Aldrich; St Louis, MO) that is used 
ubiquitously by laboratories to seal or protect containers based upon its unique properties of 
being waterproof, self-sealing, and moldable.13 Because of its physical properties and its ease 
of use, parafilm lends itself to use as an additional barrier to prevent exposure of CVL 
connections and caps to sources of infection. In infants and young children such a barrier 
could prevent exposure of CVL caps to environmental sources of infection such as the 
contents of the diaper. In six pediatric patients with total parenteral nutrition (TPN) dependent 
intestinal failure, the use of parafilm around central line hubs decreased the mean rate of 
CLABSI by about 76% (p=0.01).13 Parafilm has also been used as a standard of care CVC 
barrier in pediatric HCT patients at the Children’s Hospital of Pittsburgh since 2013, although 
it’s use has not been studied. This intervention is simple and inexpensive, and as compared 
to antibiotic prophylaxis or CHG, it will not impact on bacterial flora or antibiotics sensitivity.  
The nonrandomized study we propose will extend the use of parafilm as standard of care to 
prevent CLABSI to pediatric patients undergoing HCT and will allow us to evaluate the 
intervention in a scientific manner.   
 
3. SUMMARY OF TRIAL TO DATE AND OVERVIEW OF MODIFICATIONS TO PROTOCOL 
This trial opened in May 2015 and met the initial accrual goal (of 6-8 months) in January 2015, 
when the last of 27 patients was enrolled on study.  There are currently 8 patients who remain 
on study, and this cohort of patients will remain on study until their CVLs are removed. 
Importantly, there have been no unexpected serious adverse events (SAEs) or SAEs related 
to research in these 27 patients to date. The statistical plan will be modified to plan for interim 
data analysis on all 27 patients before CVL removal; this will include analysis of day +30 
CLABSI as well as CLABSI during initial admission period for HCT. Data will still be analyzed 
at the completion of the study for this cohort, e.g. following CVL removal. 
 
As this is a single arm pilot study, for the primary efficacy endpoint (section 1.1.2) and the 
secondary endpoint evaluating characteristics that impact the rate of CLABSI in pediatric HCT 
patients (section 1.2.2), a comparison group not receiving the parafilm intervention is needed. 
Parafilm protocol v3 (10-24-18)                                                                                                                                     7 
 

This protocol will be modified to allow for retrospective data collection in a historical cohort of 
pediatric HCT patients. 
 
Further, this study will be modified to extend the accrual goal for an additional 6-8 months. 
This modification will enable us to increase the power of this study to detect a difference in 
CLABSI between patients receiving parafilm (on current study) and receiving standard CVL 
care (historical cohort), particularly in higher risk subsets of patients (such as our youngest 
patients in diapers).    
 
4. RESEARCH DESIGN AND METHODS 
 
4.1. Study Design 
 
This will be a non-randomized pilot quality improvement initiative designed to evaluate the 
feasibility and efficacy of using parafilm as a protective central line barrier to prevent 
CLABSI in pediatric HCT patients. 
 
4.2. Study Enrollment 
 
Patients will be recruited through the Aflac Blood and Cancer Center’s Pediatric Blood and 
Marrow Transplant Division and will be enrolled by the research nurse who will confirm 
eligibility and assign a subject number.   
 
4.3. Eligibility Criteria 
 
4.3.1. Inclusion Criteria 
 
4.3.1.1. 
Must be between the age of 0 and 21 years at the time enrollment 
 
4.3.1.2. 
Must be underdoing allogeneic or autologous HCT for a malignant or non-
malignant disorder 
 
4.3.1.3. 
Must have or be scheduled to have a tunneled CVC 
 
4.3.2. Exclusion Criteria 
 
4.3.2.1. 
Patients undergoing other interventions to prevent CLABSI (e.g. COG 
ACCL1034 with CHG, antimicrobial lock therapy, etc.) are ineligible. 
 
4.3.2.2. 
Patients who only have a port are ineligible. 
 
4.4. Comparison Group 
 
Data will be collected in a retrospective fashion from a historical cohort of pediatric HCT 
patients receiving standard of care CVL care. This will include patients undergoing HCT 
during the same period of time that the study is open, but that do not either consent or 
assent to participate on study. Additionally, this will include patients undergoing HCT 
during the same calendar months 1 year prior and for the initial months preceding the 
study period. For example, for the initial cohort of 27 patients enrolled over the 8 month 
period of May 2015 to January 2016, we will compare to historical cohorts both from May 
Parafilm protocol v3 (10-24-18)                                                                                                                                     8 
 

2014 to January 2015 and from the immediately preceding 8 months (October 2014 to 
May 2015).  
 
 
 
 
5. TREATMENT PLAN 
 
5.1. Overview 
 
This is a non-randomized, open-label pilot quality improvement initiative to evaluate the 
feasibility and efficacy of using parafilm as a protective barrier to prevent CLABSI in 
pediatric HCT patients with CVCs. All Aflac HCT patients with central lines who do not 
meet exclusion criteria will have parafilm applied to their CVC at the time of admission for 
HCT. Parafilm will be maintained on the CVC and routine CVC care will be continued, per 
institutional standard of practice, until the CVC is removed. Prior to discharge from the 
inpatient HCT unit, at home caregivers will be taught how to apply and maintain parafilm 
on the line so the barrier is maintained as an outpatient. 
 
To track inpatient compliance, a nurse and physician will document the application of 
parafilm to the CVC on a weekly basis during interdisciplinary inpatient line rounds on a 
spreadsheet. To facilitate adherence to the intervention and to quickly identify any 
practical concerns, nursing will confirm that parafilm is being used on a patient’s line 
during daily rounds when lines and drains are discussed and will document appropriate 
application to each lumen on a daily basis in the EMR. Any non-compliance discussed 
during daily rounds will be documented.  To track outpatient compliance, the clinic nurse 
or physician/advanced practice practitioner will document correct application of parafilm 
during all outpatient clinic visits. Parent/guardian will maintain a log documenting 
application of parafilm at home which will be reviewed at the subsequent outpatient clinic 
visit.  
 
5.2. Concomitant Treatment Restrictions 
 
Standard CVC care should be per institutional guidelines (see Appendices I-IV for CHOA 
Standard Operating Procedures for CVC care).   Patients may receive systemic anti-
fungal therapy (for prophylaxis or treatment) and systemic antibiotics (for treatment) 
without any restrictions. 
 
5.3. Schedule for Parafilm 
 
Nursing (or parent/guarding during outpatient period) will apply pre-cut, single use 
sections of parafilm over the CVC hub (if not connected) or around the CVC hub 
connection (if connected). A new section of paraflim should be reapplied approximately 
once per day as well as following any break into the CVC or CVC disconnection. A new 
section of parafilm may be reapplied at the discretion of the caregiver or medical provider 
(e.g. if concern that it may not be applied properly or that it is coming off). 
 
5.4. Training and Education on Parafilm Use 
 
Inpatient and outpatient HCT nurses will receive formal education on the proper use and 
application of parafilm and documentation of its use, prior to the opening of this study. 
Upon admission for HCT, patients and their caregivers will also receive training on the 
Parafilm protocol v3 (10-24-18)                                                                                                                                     9 
 

use/application and documentation and such training will be repeated prior to discharge. 
Ongoing education will be provided during visits to the outpatient clinic. 
 
5.5. Positive Blood Culture 
 
If treatment for a positive blood culture requires line removal and the line is replaced (or 
if the CVC is removed for any reason and not replaced), the patient will not be followed 
for CLABSI beyond two days from CVC removal.  These patients will continue to be 
followed through day 100 for clinical outcomes/endpoints. 
 
6. AGENT INFORMATION 
 
Parafilm 
 
6.1. Source 
 
Parafilm is a plastic film with paper backing that is made from paraffin and has unique 
properties including being waterproof, self-sealing, moldable and translucent.  It is able 
to be stretched to 3-4 times its original size without breaking.  It is primarily used in 
laboratories to seal containers from outside contamination, but it has been shown to 
decrease the incidence of CLABSI in parenteral nutrition dependent pediatric patients 
with intestinal failure when used as a protective barrier at the CVC hub.13   
 
6.2. Toxicity 
 
No known toxicity when used as a CVC protective barrier, although the experience is 
small.  However, toxicity is not expected given that the parafilm will be used only as a 
protective barrier on the outside of the CVC. 
 
6.3. Formulation and Stability 
 
Parafilm is 0.005 inches thick and is supplied in 4 inch wide, 250 foot long rolls.  
Recommended storage parameters include 50% relative humidity and temperature 
ranging from 7-32 degrees Celsius, where it can be stored for up to 3 years.  
 
6.4. Supplier 
 
Parafilm is supplied by Sigma-Aldrich (St Louis, MO) and is commercially available. 
 
7. EVALUATIONS 
 
7.1. History and Demographic Information 
 
Baseline demographic data will be collected including age, race, gender, performance 
status, height and weight, diagnosis, presence of severe malabsorption (e.g. short gut 
syndrome), presence of stoma (e.g. colostomy or ileostomy), and previous BSI 
(particularly within 30 days prior to enrollment).  HCT related variables will also be 
collected, including donor type, stem cell source, HLA match, conditioning regimen, and 
indication for HCT. The identical data will be collected from the historical cohort in a 
retrospective manner. 
Parafilm protocol v3 (10-24-18)                              
10 
 

 
7.2. Clinical Information 
 
Clinical data will be collected including positive blood cultures (number; see section 7.3 
below), dates of administration of TPN, date of first ANC <500, date of neutrophil 
engraftment (first of three consecutive days when ANC >500), date of platelet 
engraftment (first day with platelet >20,000 without transfusion in the preceding 7 days), 
hospitalizations (reasons for hospitalization and dates of admission and discharge), ICU 
admissions (reasons for admission and dates of admission and discharge), use of 
systemic antibiotics or antifungals (with dates and types), GVHD prophylaxis, and 
development of GVHD (with date of diagnosis) and treatment, if applicable.  CVC specific 
data will be collected including date of placement, type of line, number of lumens, date of 
removal, reason for removal, and date of repair, if applicable. The identical data will be 
collected from the historical cohort in a retrospective manner. 
 
7.3. CLABSI 
 
Patients will be followed for BSI throughout the study period (from enrollment through 
CVC removal).  Data on all BSI will be collected including date of culture, CVC status 
(present or absent), inpatient or outpatient status, concurrent infections at other sites of 
the body, and concurrent positive cultures at other sites of the body.  Data will be reviewed 
to determine if the BSI meets criteria for CLABSI, including MBI-LCBI, according to CDC 
definitions (see section 13). The identical data will be collected from the historical cohort 
in a retrospective manner. 
 
7.4. Compliance Data 
 
Data will be collected on a periodic basis on both inpatient and outpatient compliance.  
Inpatient compliance will be documented by a nurse and physician on a weekly basis 
during interdisciplinary inpatient line rounds and will be documented by the patient’s nurse 
on a daily basis in the EMR. Outpatient compliance will be documented during all 
outpatient clinic visits by the clinic nurse or physician/advanced practice practitioner.  
Compliance will be documented as “yes” (parafilm in place), “no” (parafilm not in place), 
or “yes-inc” (parafilm applied but is applied incorrectly, not fully intact, or visibly 
contaminated). Caregivers will document use of the parafilm barrier by making a tally 
mark on a provided log. Every attempt will be made to collect the log at the end of 
treatment, but in the event that the log is unable to be collected, this will not be considered 
a study deviation. 
 
8. CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA 
 
8.1. Criteria for Removal from Protocol Therapy 
 
8.1.1.1. 
Physician concludes removal from protocol therapy is in the patient’s best 
interest 
8.1.1.2. 
Patient or patient’s guardian refuses to use parafilm. In this case, the parent 
(or patient, if over 18 years old) must sign a form acknowledging that they 
acknowledge that the use of parafilm is our departmental standard of practice 
and that not using it may increase their risk for CLABSI.  
 
Parafilm protocol v3 (10-24-18)                             
11 
 

8.2. Off Study Criteria 
 
8.2.1.1. 
Completion of intended data collection and assessments 
8.2.1.2. 
Patient is lost to follow up 
8.2.1.3. 
Death 
 
Patients who require admission to the intensive care unit (e.g. PICU) will not be 
removed from study. It is acceptable to not apply parafilm while in the PICU. 
 
9. STATISTICAL CONSIDERATIONS 
 
9.1. Statistical Design 
 
 
This is a non-randomized pilot quality improvement initiative to assess the feasibility and 
efficacy of using parafilm to prevent CLABSI in pediatric HCT patients.  Every patient 
admitted to the Aflac HCT inpatient unit on the HCT service will have parafilm applied to 
and maintained on their CVC from the time of admission to the time of line removal.  
 
9.2. Patient Accrual and Expected Duration of Trial  
 
The initial accrual period for this study was 8 months, and the study will be reopened for 
an additional up to 8 months. Follow up will occur until the last patient enrolled has their 
CVC removed, is taken off study, or is discharged from the BMT service, whichever 
occurs first. Total study duration is expected to be an additional 9-12 months, based on 
the typical length of time BMT patients retain their CVC (3 months). 
 
9.3. Statistical Analysis Methods 
 
9.3.1. Study Endpoints 
 
 
The primary outcome measure is compliance with the intervention, which is 
defined as the percentage of catheter days that patients had parafilm correctly 
applied and intact during the study period. Inpatient and outpatient compliance will 
be measured separately. For both inpatient and outpatient compliance, there will 
be two measures: reported and observed. In the inpatient setting, reported 
compliance will be measured during daily discussions of parafilm at patient care 
rounds and by daily recording of the nurse in the EMR (by lumen). Nurses will 
report whether or not parafilm is in use for a given patient or if parafilm was not 
intact or incorrectly applied during the preceding day. For each patient, parafilm 
status will be recorded as “yes,” “no,” or “yes-inc,” (if parafilm was incorrectly 
applied or applied but not intact). The percentage of catheter-days with intact, 
correctly applied parafilm, as reported by nursing staff, will be calculated. 
Observed compliance will occur during weekly line rounds. Again, rounding 
providers will indicate whether a patient’s parafilm is intact and correctly applied, 
not applied, or incorrectly applied or not intact. The percentage of “observed 
catheter-days” where patients had correct use of intact parafilm will be calculated. 
For outpatient reported compliance, parents will provide their logs to outpatient 
staff who will document a summary measure of the number of days parafilm was 
correctly in use/intact vs not in use or incorrectly in use/not intact. For example, if 
Parafilm protocol v3 (10-24-18)                              
12 
 

Patient A was last seen in clinic 4 days ago on day -4 (today is day 0), and Patient 
A’s mom recorded that parafilm was intact on days -3 and -2 but yesterday she 
found the parafilm off, nursing would record “yes” for 2 days and “no” for 1 day. 
The percentage of catheter-days where parafilm was intact will again be 
calculated. For observed compliance, the outpatient nurse will record whether the 
patient’s parafilm was correctly applied/intact (yes), not applied (no), or incorrectly 
applied/not intact (yes-inc) at the beginning of the visit. The percentage of 
outpatient “observed catheter-days” where parafilm was correctly in use/intact will 
be calculated. 
 
Additionally, CLABSI rate (total number of CLABSI/1000 catheter-days) will be 
calculated and compared to pre-intervention CLABSI rate in Aflac HCT patients 
over a similar time period (historical cohort). A stratified analysis will be performed 
to assess the rate in allogeneic vs autologous HCT recipients. CLABSI is defined 
as the identification of a bacterial infection from a blood culture drawn from a CVC 
in the absence of a primary source of infection from another body site (e.g. 
pneumonia, wound, skin abscess), in accordance with the CDC definition. Time is 
measured in catheter-days, wherein only the line most at risk for infection is 
counted in patients who have multiple CVCs. Catheter-days start at the time of 
enrollment or line placement, whichever occurs later. Secondary endpoints include 
number of antibiotic treatment courses per patient, total duration of antibiotic 
treatment exposure (excluding prophylactic antibiotics), number of ICU admissions 
secondary to sepsis, death from infection, death from any cause, total amount of 
parafilm used and associated expense, and subjective measures of caregiver 
perception of parafilm (ease of use, effectiveness, etc). 
 
9.3.2. Sample Size and Power Consideration 
 
 
Because CLABSI is a rare event in a relatively small population, calculations of 
sample size based on a normal distribution are invalid. As a quality improvement 
initiative, this intervention will be applied to all pediatric HCT patients as the 
standard of practice. We will accrue patients to include in the dataset for analysis 
of feasibility and efficacy during the first 6-8 months.  
 
9.3.3. Analysis Plan 
 
 
Primary outcome (Parafilm Compliance): The percentage of catheter-days 
where parafilm was correctly used and intact (both reported and observed 
compliance) for inpatients and outpatients will be reported.  
 
Secondary outcomes: For CLABSI rate, a univariate Poisson Regression Model 
or a Negative Binomial Model (depending on the results of goodness-of-fit tests) 
will be used to compare CLABSI rate before and after the use of parafilm and the 
Χ2 test of significance will be reported. A multivariate Poisson Regression Model 
(or Negative Binomial Model) will be used to explore the covariates that may 
influence CLABSI rate, such as type of HCT (allogeneic vs autologous), ANC, 
GVHD, compliance with parafilm, etc, and the Likelihood Ratio Test will be used 
to assess the relative contribution of individual covariates. Additionally, descriptive 
statistics reporting the total number of antibiotic courses, length of antibiotic 
exposure (days), total number of ICU admissions for sepsis, death from infection, 
Parafilm protocol v3 (10-24-18)                             
13 
 

and death from any cause both pre- and post-intervention will be reported and 
between groups differences will be assessed using two-sample T-tests to compare 
the means of these outcomes. Finally, descriptive statistics of the subjective data 
collected from provider and caregiver surveys regarding parafilm ease of use, 
perceived benefit, and other parameters will be reported. The Kruskal-Wallis Test 
will be used to compare the responses from nursing surveys to those from parental 
surveys.  
 
10. ADVERSE EVENT REPORTING 
 
10.1. 
Common Toxicity Criteria for Adverse Events (CTCAE) 
 
Adverse events will be described using event terms and severity grading from the 
National Cancer Institute (NCI) CTCAE version 4.0. Adverse events will be characterized 
by severity grading, attribution (relationship to study treatment), and expectedness 
(based upon prior experience). 
 
10.2. 
Reporting Requirements 
 
All unexpected serious adverse events (SAEs) or SAEs related to research that occur 
through completion of study should be reported within 5 business days.  Fatal events 
must be reported within 24 hours of knowledge of the event.  Unexpected problems that 
are not AE should reported within 5 business days. Documentation of SAE should be 
submitted to aflacpi@choa.org. The IRB should be notified of reported SAEs and 
unexpected problems in accordance with IRB guidelines.  
 
11. CLABSI 
 
Patients will be followed for BSI throughout the study period, and each BSI will prompt 
additional data collection (see section 7.3).  CHOA Infection Control (Lea Kendrick, 
epidemiologist) will determine whether the BSI meets criteria for CLABSI (or MBI-LCBI; 
according to CDC definitions).   
 
11.1. 
CDC Criteria for CLABSI 
 
The most recent CDC definitions will be used for determining CLABSI 
(http://www.cdc.gov/nhsn/PDFs/pscManual/4PSC_CLABScurrent.pdf). 
 
11.2. 
BSI Committee 
 
Determination of CLABSI is an ongoing occurrence happening in parallel to this 
research study by the Aflac Cancer and Blood Disorders Center BSI Committee.  
The BSI Committee meets biweekly to discuss every BSI occurring in an Aflac 
patient to review clinical details and to determine if any events could have been 
prevented. The BSI Committee also meets monthly for a BSI Prevention Taskforce 
Meeting during which monthly CLABSI rates are tracked and discussed and quality 
initiatives are discussed, including this study. 
 
 
 
Parafilm protocol v3 (10-24-18)                             
14 
 

 
 
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1. 
Vital signs: central line-associated blood stream infections--United States, 2001, 2008, 
and 2009. MMWR Morbidity and mortality weekly report 2011;60:243-8. 
2. 
Busca A, Saroglia EM, Giacchino M, et al. Analysis of early infectious complications in 
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Parafilm protocol v3 (10-24-18)                              
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