Original Investigation
Dialysis Catheter–Related Bloodstream Infections:A Cluster-Randomized Trial of the ClearGuard HD Antimicrobial
Barrier Cap
Jeffrey L. Hymes, MD,1 Ann Mooney, MSN, RN, CNN,2 Carly Van Zandt, MS,2
Laurie Lynch, PhD,3 Robert Ziebol, BS,3 and Douglas Killion, MBA 3
Background: The rate of bloodstream infections (BSIs) is disproportionately high in hemodialysis (HD)patients with central venous catheters (CVCs) versus those with permanent accesses, contributing to poorer
outcomes, such as increased rates of death and hospitalizations.
Study Design: 12-month, prospective, cluster-randomized, multicenter, open-label trial.
Setting & Participants: 40 Fresenius Medical Care North America dialysis facilities were matched andpaired by positive blood culture rate and number of patients with CVCs and then cluster-randomized with 20 ineach study group. 2,470 patients participated in the study (1,245, intervention group; 1,225, control group),
accruing approximately 350,000 CVC-days.
Intervention: Use of ClearGuard HD Antimicrobial Barrier Caps versus use of standard CVC caps;
assigned at the facility level.
Outcome: Primary end point was positive blood culture rate as an indicator of BSI rate.
Measurements: Positive blood cultures, hospital admissions for BSI, hospitalization-days for BSI,
intravenous antibiotic starts, and CVC-days.
Results: Baseline positive blood culture rates were similar (P 5 0.8) between groups. Use of ClearGuard
HD caps for 12 months was associated with a 56% lower BSI rate versus use of standard CVC caps (0.26 vs
0.59/1,000 CVC-days, respectively; P 5 0.01). When considering sustained use (deﬁned as last 6 months ofthe study), the intervention versus the control was associated with a 69% lower BSI rate (0.22 vs 0.72/1,000
CVC-days, respectively; P 5 0.01), 43% fewer hospital admissions for BSI (0.28 vs 0.48/1,000 CVC-days,
respectively; P 5 0.04), and 51% fewer hospitalization days for BSI (2.42 vs 4.94/1,000 CVC-days,
respectively; P 5 0.04). No device-related adverse events were reported.
Limitations: Study was open label; patients occasionally received HD at nonresearch facilities; patients did
not receive the intervention when hospitalized.
Conclusions: The ﬁndings show that use of ClearGuard HD Antimicrobial Barrier Caps, when comparedwith standard CVC caps, signiﬁcantly lowers rates of catheter-related BSIs and hospital admissions for BSI in
HD patients using CVCs.
Am J Kidney Dis. 69(2):220-227. ª 2016 The Authors. Published by Elsevier Inc. on behalf of the National
Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
INDEX WORDS: Hemodialysis; central venous catheter (CVC); chlorhexidine acetate; bloodstream infection(BSI); positive blood culture; infection prevention; end-stage renal disease (ESRD); ClearGuard HD
antimicrobial barrier cap; antimicrobial lock; catheter-related bloodstream infection (CRBSI); central line–
associated bloodstream infection (CLABSI); cluster-randomized trial.

S

igniﬁcant efforts have been made over the past 25
years to reduce the number of bloodstream infections (BSIs) that are caused by use of hemodialysis(HD) central venous catheters (CVCs) in patients with
end-stage renal disease. These efforts include theCenters for Medicare & Medicaid Services FistulaFirst initiative,1 Centers for Disease Control andPrevention (CDC) guidelines including Scrub-theHub protocol,2 education and training of health carepersonnel,3 and using antimicrobial locks.3-8 Despite
these efforts, the use of CVCs for HD continues to bea leading contributor to higher rates of BSI, hospitalization, morbidity, and mortality, as well as
increased health care costs.9,10

From 1Fresenius Medical Care North America; 2Frenova Renal
Research, Waltham, MA; and 3Pursuit Vascular, Inc, Maple Grove, MN.
Received July 12, 2016. Accepted in revised form September 12,
2016. Originally published online November 10, 2016.
Trial registration: www.ClinicalTrials.gov; study number:
NCT02604264.
Address correspondence to Douglas Killion, MBA, Pursuit
Vascular, Inc, 6901 E Fish Lake Rd, Ste 166, Maple Grove,
MN 55369. E-mail: dkillion@pursuitvascular.com

 2016 The Authors. Published by Elsevier Inc. on behalf of the
National Kidney Foundation, Inc. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
0272-6386
http://dx.doi.org/10.1053/j.ajkd.2016.09.014

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A Novel Device for Reducing BSIs

This study reports results of a novel device, theClearGuard HD Antimicrobial Barrier Cap (Pursuit
Vascular, Inc), hereinafter also referred to as the
ClearGuard HD cap, which was recently cleared formarket by the US Food and Drug Administration. As
shown in Fig 1, it is similar to a standard CVC cap,
except the ClearGuard HD cap contains a rod coatedwith the antimicrobial agent chlorhexidine acetate.
The rod extends into the CVC hub and has beenshown to reduce the presence of pathogenic organisms in the CVC lock solution proximal to the clamp
by .99.99%.11 Chlorhexidine is a nonantibiotic
antimicrobial agent; thus, the risk for developing
resistant organisms is minimal compared to the use ofantibiotics.12 In addition, it is effective against
antibiotic-resistant organisms.11 The ClearGuard HD
cap is used in the same manner as a standard CVCcap, without a change to procedural workﬂow.
The following model of the cause of catheterrelated BSI is useful for understanding the ClearGuard HD cap mode of action.8,13 Pathogenicorganisms are present in the environment surrounding
the CVC hub. Organisms may be transferred into the
hub during use and at the end of the dialysis procedure. The planktonic organisms tend to be ﬂushed
into the bloodstream, whereas the sessile organisms
tend to remain in the hub. Between dialysis sessions,any organisms in the hub are conﬁned between the
CVC cap and clamp within the lock solution, where
they can multiply and form a bioﬁlm. The clamp istypically repositioned after each dialysis session,
which eventually results in bioﬁlm distal to the clamp.
Organisms within the bioﬁlm can then multiply andcolonize the entire length of the CVC, enter the
bloodstream in increasing quantity, and eventually
overwhelm the immune system, causing a BSI.
The ClearGuard HD cap is intended to prevent thisintraluminal cascade from occurring by killing theorganisms within the lock solution proximal to theclamp, thus preventing the subsequent steps that leadto BSI. The ClearGuard HD cap does not eradicate
organisms in a previously colonized CVC and does
not address extraluminal sources of BSI.

The aim of the study was to investigate whether useof ClearGuard HD caps in HD patients is associatedwith improvements in rates of BSIs, hospital admissions for BSI, hospitalization-days for BSI, andintravenous (IV) antibiotic starts as compared withfacilities using standard CVC caps.

METHODS
DesignThis study was a prospective cluster-randomized comparativeeffectiveness trial intended to evaluate the assigned facilities’ useof the ClearGuard HD cap. A cluster was deﬁned as a pair offacilities that were matched for prestudy BSI rate and number ofpatients with CVCs using data obtained from March throughAugust 2014.
Only Fresenius Medical Care North America (FMCNA) facilities not currently participating in another study were eligible toparticipate. Forty facilities were matched and paired based on
positive blood culture rate and number of patients with CVCs, thenone of each matched facility pair was randomly assigned using acomputer-generated random number to either begin using ClearGuard HD caps (intervention group) or continue using standard
CVC caps (MPC-125 end caps; Molded Products, Inc; control
group). Facility staff members were trained on device use via agroup webinar.
The study was conducted by Frenova Renal Research, with datacollection through FMCNA’s electronic records. The study wasapproved by New England Independent Review Board (IRB# 14321), which also granted a patient informed consent waiver (TBP
reference TB14-032). The informed consent waiver resulted inbroad inclusion and ease of conducting the study. All HD patientswith a tunneled CVC within each facility were eligible to participate unless they had a known allergy to chlorhexidine. All patients with CVCs in all facilities were treated using the same
FMCNA standard best-practice policies and procedure throughout
the study.14 The only difference in intervention was the type of cap
used.
Standard policies and procedures require that clean gloves,gown, and full face shield with mask were worn during accessprocedures. Prior to accessing the CVC, the exit site wasroutinely inspected, the dressing was changed, and the site wascleaned using 2% chlorhexidine with 70% alcohol swab sticks.
The hub threads were wiped for 15 seconds using a 70% sterile
alcohol pad any time the blood lines were disconnected. Heparinized saline lock solution was used unless modiﬁed by physician order. After each dialysis session, a new pair of ClearGuard
HD caps (intervention) or standard CVC caps (control) wereplaced on the CVC hubs (typically 3 times per week). Whenclinical indications for BSI were present (eg, fever, chills, andFigure 1. Attaching ClearGuard HD Caps to a central venous catheter.
Am J Kidney Dis. 2017;69(2):220-227

221

Hymes et al
hypotension), blood cultures were collected from the CVC and/or
peripheral vein.
In order to avoid counting pre-existing BSIs, patients were
censored for the ﬁrst 21 days after entering the study. To avoid
double-counting the same BSI, patients were censored using the
CDC’s National Healthcare Safety Network2recommended 21day rule15: a positive blood culture is counted only if it occurred
21 days or more after a previously reported positive blood culturein the same patient, new positive blood culture events are based onblood cultures drawn as an outpatient or within 1 calendar day
after a hospital admission, and following a positive blood culture,
hospitalization for BSI, or IV antibiotic start, additional same-type
events are not counted for 21 days following the initial event(CVC-days are counted during this period). Patients were censoredat CVC removal, death, withdrawal from intervention, or loss tofollow-up.

Evaluation Periods
A 1-month preintervention baseline period occurred in
November 2014. Subsequently, all facilities participated in the 12month follow-up from December 1, 2014, through November 30,
2015. Every patient with a CVC who came into a study facility fordialysis received the facility’s assigned intervention.

Primary and Secondary End Points
The primary end point was comparison of the overall rate of
BSIs (represented by positive blood culture episodes divided by
CVC-days) between patients in the intervention group (ClearGuard HD cap facilities) and the control group (standard CVC cap
facilities). Greater than 93% of blood cultures were analyzed by asingle central laboratory.
Secondary end points were rates of hospital admissions andhospitalization-days for BSI (Item S1) and IV antibiotic starts.

Statistical Analysis
Because randomization was performed with the facility as thecluster, incidence rate ratios (IRRs) and corresponding 95% conﬁdence intervals (CIs) were calculated using a Poisson regression
model with a log link function and the natural logarithm of patientyears at risk for offset and adjusted for the facility cluster effect,
where each matched facility pair was considered a cluster. All
statistical analyses were performed using SAS, version 9.3 orhigher (SAS Institute Inc).

RESULTS
Cohort Population and Trends
Characteristics of the groups at baseline andthroughout the follow-up period are summarized inTable 1. Outcomes were analyzed within the subgroups of white and nonwhite participants and were
found to be comparable.
All facilities started the study simultaneously on
December 1, 2014; existing HD patients with atunneled CVC (hereafter referred to as patients with
CVCs) received the facility’s assigned intervention
at their ﬁrst dialysis session after the study start date,and new patients with CVCs coming into the facility
were added as appropriate throughout the study.
During the study period, there were 2,912 patientswith CVCs at all 40 participating facilities. Of these,
2,470 patients with CVCs dialyzed for longer thanthe 21-day censor period were included in the analysis. A breakdown of patient disposition is shown in
Fig 2.
In the 1-month baseline period prior to the start ofthe study, there were 1,229 patients (618 intervention
and 611 control) who accrued approximately 30,000
CVC-days. This was calculated without imposing 21day censoring at the beginning of the baseline period
because the intent was to understand the attributes ofthe baseline population prior to the start of the study.
During the 12-month follow-up period, the 2,470
patients in the analysis accrued approximately
350,000 CVC-days. Data are shown by quarters in
Fig 3. The ﬁrst quarter is lower than the other quarters
due to a greater number of patients censored for the
21-day period as they ﬁrst entered the study.
All patients who dialyzed for more than 21 days
and had a standard tunneled CVC were enteredinto the study. Additionally, no patients with an

Table 1. Facility and Patient Characteristics at Baseline and Follow-up
Baseline (Nov 2014)

Follow-Up (Dec 2014-Nov 2015)

Characteristic

AllIntervention Group

Control GroupIntervention Group

Control GroupNo. of facilities
No. of CVC patients
Age, yMale sex
Race
White
Black
Other
Missing

40
1,229
61.1 6 15.5
624 (51)20
618
61.5 6 15.6
321 (52)20
611
60.7 6 15.3
303 (50)20
1,245
61.5 6 15.1
654 (53)20
1,22560.6 6 15.1
666 (54)591 (48)587 (48)
24 (2)
27 (2)

295 (48)306 (50)
6 (1)
11 (2)

296 (48)281 (46)
18 (3)
16 (3)

609 (49)566 (46)
17 (1)
53 (4)

631 (52)495 (40)40 (3)
59 (5)

Diabetes
Dialysis vintage, y722 (59)
3.2 6 4.2

363 (59)
3.0 6 4.0359 (59)
3.4 6 4.3

705 (57)
2.2 6 3.7

698 (57)
2.6 6 4.0

Note: Values for categorical variables are given as number (percentage); values for continuous variables, as mean 6 standard
deviation.
Abbreviation: CVC, central venous catheter.
222

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A Novel Device for Reducing BSIs

Patients from 40 Dialysis Facilities

Treatment Group
Patients from 20 Dialysis Facilities

Control Group
Patients from 20 Dialysis Facilities

12/1/2014

568 tunneled CVC patients begin study

579 tunneled CVC patients begin study

12/2/2014 –11/30/2015

877 new tunneled CVC patients join study• 200 excluded since CVC <21 days

888 new tunneled CVC patients join study 242 excluded since CVC <21 days

Transitioned to fistula orgraft (n=509)
Left facility: e.g., death,lost to follow-up (n=264)
1,245 Patients Included in Analysis

Transitioned to fistula orgraft (n=483)
Left facility: e.g., death,lost to follow-up (n=283)
1,225 Patients Included in Analysis

Figure 2. Patient count during follow-up period for the intervention and control groups. Abbreviation: CVC, central venous catheter.

intervention group versus 0.59/1,000 CVC-days in
the control group (56% less in the intervention group;P 5 0.01), as shown in Table 2. The positive blood
culture IRR of the intervention compared to thecontrol was 0.44 (95% CI, 0.23-0.83).
Quarterly results are shown in Fig 4. The rate of
positive blood cultures between groups during thelast 6 months of the study (Fig 5) indicated a signiﬁcant difference: 0.22/1,000 CVC-days in theintervention group versus 0.72/1,000 CVC-days in
the control group (69% less in the intervention group;P 5 0.01).
In addition, subgroup analysis of de novo CVCs,
deﬁned as patients who entered the study with a new
CVC, demonstrated a signiﬁcantly lower positive
blood culture rate: 0.16/1,000 CVC-days in theintervention group versus 0.50/1,000 CVC-days inappropriate CVC were excluded from study (ie, nochlorhexidine allergies), and no device-related
adverse events were reported. There were no protocol changes during the study.
Primary Outcome: Positive Blood Cultures
During the baseline period, there was no signiﬁcantdifference between the intervention and control
groups (0.56 vs 0.60/1,000 CVC-days; P 5 0.8).
During the follow-up period, there were 153 positive
blood cultures, with 46 in the intervention group and
107 in the control group. There were 346,946 CVCdays during the follow-up period, with 169,609
CVC-days in the intervention group and 177,337
CVC-days in the control group. The resultant followup positive blood culture rate (adjusted for facility
cluster effect) was 0.26/1,000 CVC-days in the70

Treatment Group (177K CVC-days 12/14-11/15)
Total CVC-days (thousands)

60

Control Group (170K CVC-days 12/14-11/15)

50

50
46

40

36

30

45

48
43

42

37

20

10

15

15

0

Baseline

WINTERSPRINGSUMMERFALL(NOV 2014)(12/14 - 2/15)(3/15 - 5/15)(6/15-8/15)(9/15-11/15)

Figure 3. Central venous catheter (CVC)-days each period for the intervention and control groups.
Am J Kidney Dis. 2017;69(2):220-227

223

Hymes et al
Table 2. Twelve-Month Comparison of Rates for Bloodstream Infections, Cause-Speciﬁc Hospitalizations, and IV Antibiotics
Episodes/1,000 CVC-Days

Poisson Regression

Intervention Group

Control GroupIRR (95% CI)

P

0.26

0.59

0.44 (0.23-0.83)

0.01

0.28
3.24
1.68

0.47
4.68
1.78

0.60 (0.37-0.97)
0.69 (0.41-1.16)
0.94 (0.74-1.19)

0.04
0.2
0.6

Primary end point: positive blood culture episodes
Secondary end points
No. of hospital admissions for BSI
No. of hospitalization-days for BSI
No. of IV antibiotic starts

Abbreviations: BSI, bloodstream infection; CI, conﬁdence interval; IRR, incidence rate ratio; IV, intravenous.

group (4.68/1,000 CVC-days), but the difference was
not statistically signiﬁcant (31% less in the intervention group; P 5 0.2; Table 2).
Comparing the rates between groups during the last
6 months of the study (Fig 5) indicated a signiﬁcantdifference: 2.42/1,000 CVC-days in the intervention
group versus 4.94/1,000 CVC-days in the control
group (51% less in intervention group; P 5 0.04).

the control group (68% less in the intervention group;P 5 0.02; n 5 678 patients).
Secondary Outcomes
Hospital Admissions for BSI
During the baseline period, there was no signiﬁcantdifference between the intervention and control
groups (P 5 0.6) for hospital admissions for BSI.
During the follow-up period, the rate of hospital
admissions for BSI between groups (Table 2)demonstrated a signiﬁcant improvement: 0.28/1,000
CVC-days in the intervention group versus 0.47/
1,000 CVC-days in the control group (40% less inintervention group; P 5 0.04).
Comparing rates between groups during the last 6months of the study (Fig 5) indicated a signiﬁcantdifference: 0.28/1,000 CVC-days in the intervention
group versus 0.48/1,000 CVC-days in the control
group (43% less in intervention group; P 5 0.04).

IV Antibiotic Starts
During the baseline period, there was no signiﬁcantdifference between the intervention and control
groups (P 5 0.4) for new IV antibiotic starts. During
the follow-up period, there were nominally fewer IV
antibiotic starts in the intervention group (1.68/1,000
CVC-days) compared to the control group (1.78/
1,000 CVC-days), but the difference was not statistically signiﬁcant (6% less in intervention group;P 5 0.6; Table 2).

DISCUSSION

Hospitalization-Days for BSI
During the baseline period, there was no signiﬁcantdifference between the intervention and control
groups (P 5 0.7) for hospitalization-days for BSI.
During the follow-up period, there were nominallyfewer hospitalization-days in the intervention group(3.24/1,000 CVC-days) compared to the control

This prospective cluster-randomized comparativeeffectiveness study demonstrated that use of ClearGuard HD caps for 12 months was associated with a
56% lower BSI rate versus use of standard CVC caps.
We also observed a 69% lower rate of BSI(P 5 0.01), 43% fewer hospital admissions for BSI

1.0

No. of PBC episodes / 1,000 CVC-days

Treatment Group

IRR [95% CI] =0.27 [0.09, 0.82]
P = 0.02

Control Group0.8

p = 0.8
0.6

0 .5 6

IRR [95% CI] =0.74 [0.33, 1.65]
P = 0.5

IRR [95% CI] =0.34 [0.10, 1.12]
P = 0.08

IRR [95% CI] =0.60 [0.37, 0.99]
P = 0.04

0 .7 5
0 .6 6

0 .6 00 .5 40.4

0 .4 5
0 .3 3

0 .3 30 .2 60.2

0 .1 80.0

Baseline

WINTERSPRINGSUMMERFALL(NOV 2014)(12/14 - 2/15)(3/15 - 5/15)(6/15-8/15)(9/15-11/15)

Figure 4. Baseline and quarterly follow-up comparison of positive blood culture (PBC) rates for the intervention and control groups.
Abbreviations: CI, conﬁdence interval; CVC, central venous catheter; IRR, incidence rate ratio.
224

Am J Kidney Dis. 2017;69(2):220-227

A Novel Device for Reducing BSIs

Treatment Group
Control Group
IRR [95% CI] =0.31 [0.12, 0.79]
P = 0.01

0.8

IRR [95% CI] =0.57 [0.33, 0.98]
P = 0.04

Episodes / 1,000 CVC-days

Episodes / 1,000 CVC-days

0 .7 20.4

0.2

0 .2 2

6

5

IRR [95% CI] =0.49 [0.25, 0.96]
P = 0.04

4 .9 4

0.6

0 .4 80.4

0 .2 8

Episodes / 1,000 CVC-days

0.8

4

3

2

2 .4 2

0.2

1

0.0

0.0

PBCs

0

Hospital Admits for BSI

Hospital-days for BSI

Figure 5. Comparison of sustained rates (last 6 months) for positive blood cultures (PBCs), hospital admissions for bloodstream
infection (BSI), and hospitalization-days for BSI for the intervention and control groups. Abbreviations: CI, conﬁdence interval; CVC,
central venous catheter; IRR, incidence rate ratio.

(P 5 0.04) and 51% fewer hospitalization-days for
BSI (P 5 0.04) associated with facilities with sustained use of the ClearGuard HD cap versus facilities
with sustained use of standard CVC caps, where
sustained use was deﬁned as the last 6 months of thestudy.
The baseline BSI rate at facilities participating inthis study was better than the national average (0.58/
1,000 vs 0.71/1,000 CVC-days). In addition, the BSI
rate during the 12-month follow-up period at thecontrol facilities (0.59/1,000 CVC-days; Table 2)
was also better than the national average. Therefore,
results of this study are representative of what would
be expected in better-than-average facilities. The
national average BSI rate is from the 2014 national
aggregate National Healthcare Safety Network
Dialysis Event Surveillance data for “any CVC” of
0.71/1,000 CVC-days.16 This national rate represents
the aggregate pooled mean values from more than
6,000 outpatient HD facilities throughout the UnitedStates. It may be noted that the BSI rate in the control
facilities increased during the follow-up period (Fig4). Because the study started in the winter, one
possible explanation for the control arm’s increasing
positive blood culture rate over time is the seasonal
trend for the “summer bloom” of bacteremias during
the warmer months.14
This study accepted all patients regardless of CVC
vintage; thus, many CVCs were likely precolonizedwith organisms at the beginning of the study.17
Because the mode of action of the ClearGuard HD
cap is to prevent colonization and not eradicate organisms in a previously colonized CVC, it was
Am J Kidney Dis. 2017;69(2):220-227

anticipated that the ClearGuard HD cap might be lesseffective with CVCs that had previously used standard CVC caps. Based on the mode of action, efﬁcacy
was expected to improve over time as old CVCs are
replaced with new CVCs. Therefore, an analysis was
performed in quarterly increments, as shown in Fig 4.
Consistent with the mode of action, there was a lower
positive blood culture rate in the intervention versus
control group during the ﬁrst quarter, which improved
further during the second quarter and was greatest
during the third and fourth quarters. During the last 6months of the study, the positive blood culture
decrease had reached a sustained level (IRR, 0.31 forthe intervention vs control group; P 5 0.01).
The mode of action also predicts that the device
will be most effective on new CVCs that are only
capped using the ClearGuard HD cap (de novo
CVCs). Results in the de novo CVC subgroup werecomparable to results during the last 6 months of thestudy (IRR, 0.32 for the intervention vs control group;P 5 0.02). These results provide the best indication of
expected sustained performance if ClearGuard HD
caps were fully implemented as standard of careacross all dialysis centers.
Use of ClearGuard HD caps resulted in 6% fewer
IV antibiotic starts in the intervention group versus
the control group, but the difference was not statistically signiﬁcant. The reason for the smaller than expected decrease is not fully understood, but it is
known that IV antibiotics are often administeredwhen a BSI is suspected but might not be present. In
addition, IV antibiotics are administered for othertypes of infections, which are often present in this225

Hymes et al

population. Finally, in the baseline period prior to thestudy, the intervention group had a 25% higher rate of
new IV antibiotic starts versus the control group (3.32
vs 2.66/1,000 CVC-days, respectively; P 5 0.4).
In addition to the important patient-related beneﬁts
resulting from reduced BSIs and hospitalizations, theresulting economic savings for providers and payers
are substantial. Reducing catheter-related BSIs may
save dialysis providers $2,400 per BSI episode18 andsave Medicare $16,000 per BSI episode,19 primarily
due to reducing missed interventions, medication use,and hospitalization costs. This equates to a combined
per-member-per-month cost savings of $274 based on
the national average BSI rate (0.71/1,000 CVC-days)
and sustained use of the ClearGuard HD cap (IRR,0.31). If extended to all HD patients with CVCs in the
United States,20 the estimated combined savings areconservatively $300 million annually.
This study has many strengths. It was prospective
and randomized and used best-practice methods for
infection prevention in the control arm. All facilities
followed standard clinical policies and procedures
throughout the study, except for using the ClearGuard
HD cap at intervention group facilities; therefore,
results are representative of use in current clinicalpractice. Also, it was of 12 months’ duration, so
seasonal variations and sustainability were assessed.
In addition, it was larger than any reported antimicrobial lock meta-analysis study to date.4,5,21,22
The study also has limitations. It was open label,and intervention patients occasionally received dialysis at nonparticipating facilities, which likely
diminished the effectiveness of the intervention. Not
all positive blood culture measurements were
captured, such as during hospitalization; therefore,
BSI rates are under-reported. In addition, diagnosisspeciﬁc hospitalizations are not always accurately
coded and were likely underestimated due to barriers
preventing complete access to hospital discharge records23,24; however, there was no indication that potential biases were unbalanced between groups. In
consideration of these issues, the study is likely
generalizable to other dialysis facilities with similar
patient populations and intervention practices.
In summary, our ﬁndings show that the ClearGuard
HD cap, when compared to a standard CVC cap,
signiﬁcantly lowers rates of catheter-related BSI andhospital admissions for BSI, representing an important breakthrough for HD patient care in the UnitedStates.

ACKNOWLEDGEMENTS
We thank NAMSA (North American Science Associates Inc)
for performing the statistical analysis and the staff at Frenova
Renal Research for performing the study.
Support: This study was supported by Pursuit Vascular Inc.

226

Financial Disclosure: Dr Hymes is an employee of FMCNA;
Ms Mooney and Ms Van Zandt are employees of Frenova Renal
Research; Dr Lynch, Mr Ziebol, and Mr Killion are employees of
Pursuit Vascular Inc and may have patents, board membership,and stock and/or stock options.
Contributions: Research idea and study design: DK, RZ, LL,
JLH, AM; data acquisition: CVZ; data analysis/interpretation: RZ,
LL, CVZ. Each author contributed important intellectual content
during manuscript drafting or revision and accepts accountability
for the overall work by ensuring that questions pertaining to theaccuracy or integrity of any portion of the work are appropriately
investigated and resolved. The authors take responsibility that thisstudy has been reported honestly, accurately, and transparently;that no important aspects of the study have been omitted; and thatany discrepancies from the study as planned and registered havebeen explained.
Peer Review: Evaluated by two external peer reviewers, a Statistical Editor, a Co-Editor, and Editor-in-Chief Levey.

SUPPLEMENTARY MATERIAL
Item S1: Codes for hospital admission.
Note: The supplementary material accompanying this article(http://dx.doi.org/10.1053/j.ajkd.2016.09.014) is available atwww.ajkd.org

REFERENCES
1. Centers for Medicare & Medicaid Services. The Fistula First
breakthrough initiative. http://www.ﬁstulaﬁrst.org. Accessed May
25, 2016.
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