A Randomized Trial Examining Plasma Exchange Using the Becton Dickinson (BD) Catheter In an Outpatient Apheresis Unit
Phase: NA
Conditions: Plasma Exchange
Sponsor: University of Texas Southwestern Medical Center

Official title: A Randomized Trial Examining Plasma Exchange using the BD Catheter In an 
Outpatient Apheresis Unit (REPLACE) 
 
 
NCT number:  NCT04253756 
IRB Approved date: 4/22/2020 

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A Randomized Trial Examining Plasma Exchange using the BD Catheter In an Outpatient Apheresis Unit 
(REPLACE) 
 
 
PI: Tomas Armendariz BSN, RN, CMSRN, QIA 
 
Faculty Sponsor: Nicole De Simone MD 
 
Co-Investigator: DaiWai Olson, PhD, RN 
 
Research manager: Sonja Stutzman PhD 
 
Date: 11/27/2019 
 
Version: 1 
 
 

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Introduction and Purpose 
 
Nurses and apheresis technicians caring for patients requiring therapeutic apheresis 
procedures (TAP) utilize a wide range of intravenous catheters to obtain the access required to 
perform their procedures(Kalantari, 2012), (Golestaneh & Mokrzycki, 2013). The standard of 
care for our facility is to use an 18-gauge apheresis needle (Medisystems®) for the access site 
and an 18-gauge autogard catheter for the return site. Unfortunately, there is minimal literature 
defining best practices for catheter size selection(Salazar et al., 2017).  At UT Southwestern 
Medical Center, our goal is to provide peripheral therapy to reduce the need for central access, 
such as a medical ports or tunneled catheters(Spires et al., 2018).  However, the requirement for 
an 18 gauge catheter for an adequate return site, at times, rules out the patient for peripheral 
therapy(Putensen, Leverett, Patel, & Rivera, 2017).  This requires central venous access to be 
obtained, which can delay the start of the procedure.  
The lack of scientific evidence to support the use of smaller peripheral return 
catheters has increased the use of implanted ports in our institution(Putensen et al., 2017).  
The objectives of our pilot study are patient-centered and include analyzing the safety of using 
smaller peripheral return catheters without increasing the risk of hemolysis.  
Background and Significance 
TAP treats a wide range of disease processes and, in all cases, requires inlet and return 
venous access to perform the procedure. The goal of TAP is to return the patient to baseline and 
maintain independence and function. A larger needle (18 gauge) can cause more discomfort to 
the patient as well as additional scarring.  A smaller needle may present less discomfort and 
scarring to the patient. Our goal in our outpatient clinic is to minimize disruption to the patient’s 
routine and help them maintain normal activities of daily living.  
To accomplish these goals, our outpatient clinic is open Monday thru Friday offering 4 
different appointment times.  All patients that are referred to our clinic for TAP, first receive a 
vein evaluation to see if the patient is a candidate for peripheral IV therapy.  At our clinic, 
approximately 68% of our TAP’s are performed peripherally. This eliminates the risk of a central 
line infection and any alteration in activities of daily living, such as bathing(Kramer, 2016), 
(Shang, Ma, Poghosyan, Dowding, & Stone, 2014),(Keller et al., 2018; McDiarmid, 2015).  

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Our hypothesis, is that the 20-gauge BD Nexiva Diffusics catheter provides the same 
efficacy as current practice with no increase in adverse events for patients undergoing 
therapeutic apheresis.  The results from our study will be significant because if the 20 guage 
needle is equally effective for TAP, it can increase the number of patients that would be 
candidates for peripheral therapy.  Therefore, decreasing the need for central venous access, 
which place the patient at an increased risk of infection. Our study is a comparison of 2 types of 
infusion catheters.  The standard of care is an 18-gauge autogard catheter (control group) which 
will be compared to the 20-gauge BD Nexiva Diffusics (intervention).  
P – patients who require therapeutic apheresis procedures (TAP) 
I – use of 20G BD diffusics catheter during apheresis 
C – use of 18 G standard of care IV catheter during apheresis 
O – no difference in efficacy and no increase in safety events 
Concise Summary of Project 
This is a randomized pilot study of TAP using the current standard of care catheter (SOC) 
vs the BD Nexiva Diffusics Catheter. It is a single blinded, randomized study. Data will be used 
to refine and power a full randomized control trial. For this study, a sample of 33 encounters in 
each group (total of 66 encounters). Our specific aim is to test the hypothesis that the 20-gauge 
BD Nexiva Diffusics Catheter provides the same efficacy and lower pain level with no increase 
in adverse events for patients undergoing apheresis treatments. 
 
Randomization Procedure 
After an eligible participant is consented to the study the patient will be randomized 
without replacement to the use of one of the two catheters. Using a random number generator, 
numbers between (1-66) were randomly divided into two groups: SOC Control group and BD 
Intervention group (Figure 1). A study identification number (SID) key will be saved on a 
UTSW approved secure device and only the research coordinator will have access to the SID key 
showing which SID coordinates with each group. This will ensure that unblinding can occur is 
necessary and there is a backup to randomization.  
The research coordinator will have 66 randomized envelops without replacement. Half of 
the envelops wil be assigned to  18G catheter SOC (control) and the other half  be assigned to 

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20G BD Nexiva Diffusics catheter (intervention). The PI will be blinded, therefore the PI will 
pick an envelope when patients are consented and ready for treatment. Participants will be 
randomized after they have consented to the study.  Participants’ will then be randomized to one 
of the two groups again at each encounter (i.e., SOC visit). Inside the envelope it will tell the 
investigator if the patient is in the control or intervention group of the study.   
 
To promote a more representative sample, each patient may participate a maximum of 10 times.  
 
Study procedure: 
Each enrolled patient will 
participate in the study will be 
randomized at each encounter. 
During each encounter the 
following information will be 
captured: 
1. CBC 
2. Patient discomfort 
level with placement of catheter 
3. Inlet rate 
4. Return line pressures 
5. Procedures alarms 
6. Procedure total time 
7. Post procedure sample   
 
Treating nurse (RN) will start the TAPs procedure with one of the 2 catheters. During the 
intervention period, the RN will be at bedside during as it is SOC in the Apheresis unit however 
for the purpose of this study the RN will have the study data collection form (DCF, Appendix1).  
The RN will complete the pre-assessment including a pain assessment to establish pain level 
prior to procedure that is currently documented in the electronic medical record. The patient will 
be asked to self-report the pain level after the return line has been started on the visual analog 
scale (VAS) Scale from 0mm to 100mm “0 being the lowest/ no pain, 100mm being the highest 
Figure 1. REPLACE study design
 

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level of pain”.  The VAS scale will be used for both the SOC and intervention group to compare 
the pain level when starting the return line. The RN will collect a CBC before the start of the 
procedure which will be used in the programing of the TAP procedure.  The RN will start 
recording the “inlet rate, return line pressures, and alarms” every 15 minutes until the procedure 
is completed.  
Before patient disconnects, and after the completion of procedure sing the same therapeutic 
apheresis procedure access site, a blood sample will be drawn by the RN 2 lavender top tubes 
(4ml) for plasma hemoglobin test. The plasma hemoglobin test will be sent to the UTSW lab for 
analysis of hemoloysis and results will be sent back directly to the PI. Blood sample results will 
be collected by the PI or the study team in an excel spreadsheet (CRF) that will be saved on a 
secure drive on the UTSW campus. 
Hemolysis is defined as the destruction of red blood cells which leads to the release of 
hemoglobin from the red blood cells into the blood plasma. Each patient will be tested for 
hemolysis by running plasma hemoglobin test after the procedure has finished. This will be 
collected in a two lavender tops (4ml) The cost for this test is covered by sponsor and because 
the patient has an indwelling access to venous blood there will no charge for drawing the 
sample.. There is no clinical suspicion that the use of the 20-gauge BD Nexiva Diffusics Catheter 
will increase this risk. Hemolysis will be scored dichotomously as present or absent for each 
encounter.   
Pain is defined as any increase discomfort experienced by the patient associated with the 
apheresis procedure. The current standard of care is to ask the patient “are you having pain” and 
then ask them to rate the pain from 0 to 10. For this study, one additional question will be asked 
after the patient’s vein has been accessed (IV catheter in place). The patient will self-report their 
pain using a 100 mm VAS scale. “The VAS has been used by healthcare providers to measure 
the characteristics of disease severity in each patient individually”(Klimek et al., 2017) 
Currently, all peripheral apheresis patients have some pain/discomfort while having a treatment, 
however; it is usually tolerated with minimal complaints. 
Measures of Quality of Apheresis will include inlet rate, and return pressures, 
procedure time. These measures are all readily available in the electronic medical record (EMR) 
and are all currently recorded as standard of care.  

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The inlet rate is defined as the percent of patient inlet rate divided by the maximum 
allowable inlet rate. Because inlet rates are different for each type of TAP has a different 
maximum inlet rate, this will allow standardization across procedures. The max inlet rate for 
Photopheresis is 50ml/sec, the max inlet for plasma exchange is 100ml/sec inlet for red blood 
cell exchange is 55ml/sec. In addition, the inlet rate for each participant in the intervention arm 
will be compared to the average of their last 5 procedures. This measure will compare the 
efficiency of the SOC verses the intervention.  
Inclusion Criteria 
• Adult (≥18 years old) 
• Speaks and reads English 
• A patient of the Apheresis clinic at UT Southwestern University Hospital and Clinics   
• Scheduled to receive TAP (therapeutic plasma exchange, red blood cell exchange and 
extracorporeal Photopheresis) as standard of care 
Exclusion Criteria 
• Prisoners 
• Persons under the age of 18 years  
• Patient who are actively involved in chemotherapy 
Sources of Research Material 
There are three sources of data for this study: electronic medical record (EMR) and 
paper-and-pen data collection from the patient’s bedside (Data Collection form), and lab results 
provided by the UTSW laboratory via EMR.  The EMR data that will be collected will include 
demographic information such as: age, sex, race, ethnicity, and admission diagnosis.  The paper-
and pen-data collection will include the patient self-reported pain level (VAS Scale), CBC 
collection, procedure data (minutes, inlet rate, return line pressures and alarms) total procedure 
time and post procedure sample. The paper-and-pen data collection form (Appendix 1) will 
record data only during patients TAP’s encounter. Blood sample will be obtained from a SOC 
line.  An additional 8 ml’s for blood will be drawn from the patients for research purposes. 
Results from the bloodwork will be provided by the UTSW laboratory via the patient’s EMR.   

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Recruitment Methods and Consenting Process 
For this study, patients will be recruited from the Apheresis Unit at UT Southwestern 
University Hospital and Clinics by a member of the research team. A member of the research 
team will screen the electronic medical record to determine a patient’s eligibility.  If a patient 
appears eligible for the study a member of the research team will discuss eligibility criteria with 
a member of the clinical team (nurse manger, nurse, physician, resident, fellow, social worker). 
The researcher will communicate with the clinical team to ensure eligibility: adult (≥18 years 
old), speaks and reads English, admitted to the Apheresis Unit at UT Southwestern University 
Hospital and Clinics at the time of consent. All patients in this study will be able to provide self-
consent (read and speak English).  
When a patient is deemed eligible, a member of the research team will discuss consent 
and study procedures with that patient, in a place that is comfortable for the patient. After being 
approached by a member of the research team, patients will have up to next visit to consider 
participation in the study. The study team expects recruitment of 30 participants to last 
approximately 8 months. (Table 1) 
Potential Benefits 
There may or may not be a direct benefit to the participants in this study. Any additional 
blood test result that seems out of the norm will be shared with the nurse on duty or treating 
physician. We would also hope to share this with the greater research and clinical community in 
hopes of finding an alternative way for apheresis patients to have therapeutic apheresis 
procedures with less pain and no increase in adverse events. 
Potential Risks 
Risks associated with BD Cather: 
  Longer procedure time might occur if the inlet rate of the treatment is slower.  The patient 
will be informed of this during the ICF process. With smaller catheters there’s a risk of not 
obtaining the appropriate return rate for the patient.  When the return rate is out of the SOC 
parameters the SOC apheresis equipment (Optia or Cellex) will alarm.  If the alarm sounds 3 times 
the RN will decrease inlet rate by 5 ml/sec until the minimum threshold is reached (if needed), 
which is 50 ml/sec for plasma exchange and 35 ml/sec for RBC exchange and 20 ml/sec for 
photopheresis. If the alarm continues to when the minimum threshold is reached the catheter will 

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be replaced with the SOC 18-gauge catheter. Obtaining blood samples may cause some discomfort, 
feeling lightheaded, fainting, bruising, clotting, and bleeding from the site of the needle stick and, 
in rare cases, infection. The risks are mitigated by drawing blood from a line that has already been 
established as part of SOC. 
There is a low risk of breach in confidentiality. Subjects will be assigned individual study 
identification (SID) numbers and no personal identifiers will be included in the final summary.  
Patients who are randomized to the 20-guage needle group and who fail the intervention 
will be given the 18-guage standard of care needle. At the patient’s next visit, the patient will  once 
again be randomized. If the patient is randomized into the 20-guage needle arm and fails the 
intervention a second time, the patient will be removed from the study.  
 
Procedures to Maintain Confidentiality 
Study participants will be given a study identification (SID) number. Only the approved 
study personnel and the principal investigator have access to the database linking the SID to the 
patient name. This database is kept on a protected drive on a password protected computer. Paper 
or hard copy participant records will be kept in a locked file cabinet in a locked office. If any 
identifying information is transmitted, it will be done so via secure e-mail and/or dedicated fax 
machines.  
Statistical Analysis Plan 
All data will be first collected on the DCF (Appendix I) and then entered into an 
electronic spreadsheet (e.g., MS Excel) which will be converted to SAS v 9.4 for analysis. All 
statistical analyses will be performed at UTSW in a location with secure data encryption 
capability. Initially, the data will be summarized first using standard measures of central 
tendency (mean, median, standard deviation, and interquartile range) for each variable. These 
will be examined to support the assumption of being approximately normally distributed. 
Baseline characteristics will be summarized using appropriate parametric and non-parametric 
measures. 
The primary hypothesis is that the 20-gauge BD Nexiva Diffusics catheter provides the 
same efficacy of current practice with no increase in adverse events for patients undergoing 
therapeutic apheresis. This will be examined in 2 steps. First, ANOVA will be used to explore 

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efficacy wherein efficacy is represented by 1) the plasma hemoglobin value, and 2) the amount 
of time (minutes) required to complete a TAP. Hence models will be constructed to compare the 
mean plasma hemoglobin values by group, and to compare the mean number of minutes to 
complete TAP by group. Second, ANOVA will be used to compare the mean number of adverse 
events subjects experience in each group (intervention vs control).  
Finally, a planned secondary analysis is to examine if the percent of lumen occupied by 
the return catheter is associated with return pressures. The suggested standard is that a catheter 
occupies < 45% of the inner-lumen diameter (measured with ultrasound). Return pressures >400 
mm Hg are considered problematic. Chi-square analysis will be used to explore the odds of 
experiencing a return pressure > 400 mm Hg when the return catheter occupies <45% of the 
inner-lumen diameter.  
 
Project Timeline 
Item 
Month 1-2 
Month 3-6 
Month 4-8 
Month 9-11 
Month 12-18 
IRB approval 
X 
 
 
 
 
Consent/ 
Enrollment 
X 
X 
 
 
 
Randomization 
X 
X 
X 
X 
 
Data collection 
X 
X 
X 
X 
 
Manuscript 
prep 
 
 
 
X 
X 
Study closeout 
 
 
 
 
X 
 
Enrollment of first patient (month 1), enrollment of the last patient (month 12), 
completion of data analysis (month 14), and manuscript submission (month 18). The apheresis 
team see approximatley 3000 TAP treaments each year. Of these, approximately 1500 
encounters will meet the primary inclusion criteria. We anticipate that it will take less than 1-
year to complete the study.  
 
Future directions  

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The intention of this pilot study is to test the 20-gauge BD Nexiva Diffusics Catheter 
performance and efficacy. The findings from this study will be used to provide additional 
preliminary data to BD to support a National Institutes of Health or Agency for Healthcare 
Research and Quality (AHRQ) application (pending 2017 AHRQ funding announcements). 
Stakeholder feedback will be provided through an optional de-identified report to all patients and 
families.  
Presentation of data 
It is anticipated that the results from this study will be presented to American Society for 
Apheresis at their annual convention. The results will also be summarized in a manuscript and 
submitted for peer-review publication to Journal of Clinical Apheresis. 
 
 

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Appendix 1 
 
A Randomized Trial Examining Plasma Exchange using the BD Catheter In an Outpatient Apheresis Unit  
The “REPLACE” study 
 
 
Date _______________ 
SID __________  Procedure Type ___________ 
 
Instructions:  
Please complete the following form except for the VAS scale. Must be 
completed by patient to measure the characteristics of pain severity. 
Please circle option that apply.   
Collect CBC 
Yes 
No 
Catheter type 
18 GA BD Autogard 
20 GA BD Nexiva Diffusics 
Vein diameter w/tourniquet: 
 
___________________ 
Vein diameter w/o turniquet: 
 
_____________________ 
Vein diameter Procedure Running: 
 
_________________________ 
Asses pain after return placement 
Please rate your current pain by drawing a vertical line across the bar below 
 
 
Procedure data 
          Procedure start time: 
 
Minutes 
Inlet rate 
Return 
line 
pressures 
Alarms 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not At All Severe 
Extremely Severe 
100 (mm) 
0 (mm) 
Patient Sticker 

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References 
 
Golestaneh, L., & Mokrzycki, M. H. (2013). Vascular access in therapeutic apheresis: update 
2013. Journal of clinical apheresis, 28(1), 64-72.  
Kalantari, K. (2012). The choice of vascular access for therapeutic apheresis. Journal of clinical 
apheresis, 27(3), 153-159.  
Keller, S. C., Williams, D., Rock, C., Deol, S., Trexler, P., & Cosgrove, S. E. (2018). A new 
frontier: Central line–associated bloodstream infection surveillance in home infusion 
therapy. American journal of infection control, 46(12), 1419-1421.  
Klimek, L., Bergmann, K.-C., Biedermann, T., Bousquet, J., Hellings, P., Jung, K., . . . Stock, P. 
(2017). Visual analogue scales (VAS): Measuring instruments for the documentation of 
symptoms and therapy monitoring in cases of allergic rhinitis in everyday health care. 
Allergo journal international, 26(1), 16-24.  
Kramer, N. (2016). Monitoring Central Line-Associated Bloodstream Infections (CLABSI) in 
Home Infusion. Infusion, 22(4), 35-44.  
McDiarmid, S. (2015). Reduce the risk of infection by reducing the need for central lines: using 
ultrasound guidance to establish peripheral access in patients with sickle cell disease 
undergoing red cell exchange apheresis. Journal of clinical apheresis, 30(2), 98-99.  
Putensen, D., Leverett, D., Patel, B., & Rivera, J. (2017). Is peripheral access for apheresis 
procedures underutilized in clinical practice?—A single centre experience. Journal of 
clinical apheresis, 32(6), 553-559.  
Salazar, E., Garcia, S., Miguel, R., Segura, F. J., Ipe, T. S., & Leveque, C. (2017). Ultrasound‐
guided peripheral venous access for therapeutic apheresis procedures reduces need for 
central venous catheters. Journal of clinical apheresis, 32(4), 266-269.  
Shang, J., Ma, C., Poghosyan, L., Dowding, D., & Stone, P. (2014). The prevalence of infections 
and patient risk factors in home health care: a systematic review. American journal of 
infection control, 42(5), 479-484.  
Spires, S. S., Rebeiro, P. F., Miller, M., Koss, K., Wright, P. W., & Talbot, T. R. (2018). 
Medically attended catheter complications are common in patients with outpatient central 
venous catheters. infection control & hospital epidemiology, 39(4), 439-444.  
 
Total Procedure  time:  
Procedure end time: 
Final Inlet Volume/Blood 
Processed: 
 
Collect post proceduer  
Plasma Hemoglobin 
Yes 
No