International Journal of Nephrology and Renovascular Disease

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Open Access Full Text Article

Use of the Tego needlefree connector
is associated with reduced incidenceof catheter-related bloodstream
infections in hemodialysis patients
This article was published in the following Dove Press journal:
International Journal of Nephrology and Renovascular Disease
3 April 2014
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Steven M Brunelli 1
Levi Njord 2
Abigail E Hunt 1
Scott P Sibbel 1
DaVita Clinical Research ®,Minneapolis, MN, USA; 2DaVita
HealthCare Partners, Inc, Denver,
CO, USA
1

Background and objectives: Catheter-related bloodstream infections (CRBSIs) are ­common
in hemodialysis patients using central venous catheters, and catheter occlusion also occurs
frequently. The Tego needlefree connector was developed to reduce the incidence of thesecomplications; however, existing studies of its effectiveness and safety are limited.
Materials and methods: This retrospective analysis compared outcomes among patients ofa large dialysis organization receiving in-center hemodialysis using a central venous catheterwith either the Tego connector or standard catheter caps between October 1 and June 30, 2013.
Incidence rates for intravenous (IV) antibiotic starts, receipt of an IV antibiotic course, positive
blood cultures, mortality, and missed dialysis treatments were calculated, and incidence-rate ratios(IRRs) were estimated using Poisson regression models. Utilization of erythropoiesis-stimulating
agents (ESAs) and thrombolytics was described for each patient-month and compared using
mixed linear models. Models were run without adjustment, adjusted for covariates that were
imbalanced between cohorts, or fully adjusted for all potential confounders.
Results: The analysis comprised 10,652 Tego patients and 6,493 controls. Tego use was independently associated with decreased risk of CRBSI, defined by initiation of IV antibiotics (adjusted
IRR 0.92, 95% confidence interval [CI] 0.87–0.97) or initiation of IV antibiotic course (adjusted
IRR 0.89, 95% CI 0.84–0.95). Tego use was independently associated with decreased rate of
missed dialysis treatments (adjusted IRR 0.98, 95% CI 0.97–1.00); no significant ­difference
between Tego and control cohorts was observed with respect to mortality. Tego use was ­associatedwith decreased likelihood of thrombolytic use (adjusted per-month probability of 5.6% versus
6.2% for controls) and lower utilization of ESAs in study months 7–9.
Conclusion: Use of the Tego connector may reduce the risk of CRBSI and result in lower utilization of thrombolytics, antibiotics, and ESAs, as well as fewer missed dialysis treatments.
Keywords: catheter, dialysis, end-stage renal disease, ESA, infection, mortality

Introduction

Correspondence: Steven M Brunelli
DaVita Clinical Research®, 825 South
8th Street – Suite 300, Minneapolis,
MN 55404, USA
Tel +1 781 292 0901
Fax +1 877 683 2671
Email steven.brunelli@davita.com

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http://dx.doi.org/10.2147/IJNRD.S59937
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Catheter-related bloodstream infections (CRBSIs) are a common complication of­long-term use of central venous catheters (CVCs) for vascular access in end-stage renal
disease (ESRD) patients receiving hemodialysis (HD). Data from the United States
Renal Data System suggest that from 2000 to 2008, hospitalizations for ­bacteremia
and sepsis increased, a change that parallels the increase in use of CVCs among
US HD patients. From 2008 onward, rates have remained high: at approximately
300 admissions with bacteremia/sepsis per 1,000 patient-years in 2011.1 Aside fromhaving a direct impact on patient well-being, catheter infection, including ­subclinicalDovepress

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Brunelli et alcolonization, also contributes to systemic inflammation,
which has important downstream consequences, including
increased dose requirements for erythropoiesis-stimulating
agents (ESAs).2,3
Catheter occlusion due to thrombosis is another common issue, and can result in lower blood flow and dialysis
inadequacy.4 To prevent catheter dysfunction caused bythrombotic occlusions, standard protocols require that
CVCs are locked with heparin after completion of atreatment.5,6 However, a number of concerns have beenraised regarding heparin use: dosing errors or overfillingof the catheter lumen can result in systemic anticoagulationand heparin-induced thrombocytopenia, and heparin has
also been shown to promote Staphylococcus aureus biofilm
formation in vitro.7,8Recent initiatives to reduce rates of CVC use in HD
patients have had some success,9,10 although rates remain
unacceptably high.1 A variety of factors contribute to thehigh rates of CVC use in HD patients, including lack ofpredialysis care, maturation failure for arteriovenous fistulas
and grafts, patient resistance to permanent access placement,
and fistula stenosis and thrombosis.11 Therefore, despite
concerted efforts to reduce catheter use, a proportion of HD
patients will remain reliant on this access type.
The Tego® needlefree hemodialysis connector (ICU
Medical, Inc., San Clemente, CA, USA) was developed toreduce catheter-related infections and thrombotic occlusions
associated with the use of CVCs for HD.12 The Tego connector device has been cleared by the US Food and Drug
­Administration, and can be flushed and locked with either
saline or heparin. Between November 2010 and July 2011,
DaVita® implemented use of the Tego connector in nearly
70% of its CVC patients. Implementation was not universal,
owing to delayed or absent uptake by individual facilities.
However, within individual facilities, Tego connectors arenearly universally used or universally not used. The resulting
natural experiment forms the basis for rigorous evaluationof the comparative effectiveness of Tego versus standard
catheter caps, an analysis that is lacking from the publishedliterature; available studies have been small, and yielded
equivocal results.13,14 The current retrospective, observational
analysis was designed to assess the comparative effectivenessand safety of Tego connectors, relative to standard catheter
caps, in a large, real-world, in-center HD patient population
at a large dialysis organization (LDO) with respect to rates
of catheter-related bacteremia, missed treatments, death, andutilization of ESAs and thrombolytics.

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Materials and methods
Study setting and patientsThe goal of this retrospective analysis was to assess the comparative effectiveness of Tego versus standard catheter caps.
In order to minimize any bias due to events that preceded thestudy, analysis was limited to catheters that were newly placed
during the study period. Although catheter implantation-site
information was not available for study patients, tunneledcatheters within the upper central vasculature are almost
universal within LDOs. Patients were therefore considered
if they: 1) underwent CVC placement during the period from
October 1, 2012 to June 30, 2013; 2) received in-center HD
via said CVC for at least 21 days thereafter (to avoid consideration of temporary catheters that may not have been left inplace long enough to manifest adverse events); 3) had available electronic health-record data regarding the catheter-cap
type used (ie, Tego or standard catheter cap); and 4) did notswitch (in either direction) between standard catheter cap
and Tego-connector use within 21 days of first in-center HDwith the new catheter. CVCs in place prior to October 1, 2012were not considered. However, patients with prior catheters
were eligible for study if they underwent placement of a newcatheter during the study period and met the aforementioned
criteria; in these instances, patients entered the study at thetime of the new catheter placement. Catheters with standard
caps were typically locked with unfractionated heparin, andcatheters with Tego connectors were locked with saline, as
per LDO policies and procedures.

Exposure
Patients were classified according to the catheter cap
type that was placed at the dialysis session following­catheter placement (Tego versus standard catheter cap). By­inclusionary restriction, the catheter type was maintained forat least 21 days thereafter (see earlier). Thereafter, patientsremained assigned to their starting group for the remainderof the study. Patients who crossed over between exposuregroups thereafter were censored 21 days after crossover;this lagged censoring was used to account for delays in­disease manifestation, as infections may have initiated during
use of the original cap type but not manifested until after­switching. At-risk time otherwise continued until ­censoringfor change in dialysis access type, transfer of care, change
in modality, transplant, withdrawal from dialysis, or end of
the study (June 30, 2013). Patients could therefore contribute a minimum of 21 days and a maximum of 270 days of
at-risk time.

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Outcome definitions
Occurrence of CRBSI was identified for each patient using threeoperational definitions: intravenous (IV) antibiotic start, receipt
of an IV antibiotic course (defined as patient having received
two or more doses of IV antibiotic within a 21-day period), or
confirmed positive blood culture. Blood cultures were groupedby a 21-day rule stipulating that any positive blood cultures
were considered part of the same infection if the draw dates
were #21 days apart. Of particular note, many dialysis patients(particularly when faced with more severe symptoms) will seek
urgent care outside the dialysis facility (eg, emergency department, hospital); blood culture results from such visits are notavailable through LDO electronic health records. Therefore,
outcomes based on LDO records of positive blood cultures areinsensitive measures of CRBSI, and were considered subordinate to CRBSI definitions based on IV antibiotic utilization,
particularly initiation of antibiotic courses.
Death data were abstracted from the LDO electronic
health record system. Missed treatments were also abstracted
from LDO electronic health records. Missed treatment rate
is important in its own right, because of implied effects on
the adequacy of renal replacement therapy and also as asurrogate of hospitalization; sensitivity of LDO electronic
health records for hospitalization events and particularcause-specific hospitalization events is poor. ESA andthrombolytic utilization were abstracted from LDOs’ treatment records.

Statistical analysis
Incidence rates (death, hospitalization, missed dialysis sessions, CRBSI under each definition) were calculated as thenumber of events divided by time at risk. Incidence rate ratios(IRRs) were estimated using Poisson regression models.
Drug use or nonuse (for ESAs and thrombolytics) was
described for each patient-month and compared using generalized estimating equations with logit link to a binomial
distribution. ESA dose was considered among ESA users
as the mean per-treatment dose for each patient-monthand compared using mixed linear models. Tego exposure­(dichotomous) was set as the primary fixed-effect term.
­Random patient intercepts were included, allowing for
estimation of ESA dose at the patient level. Additional
fixed-effect terms were entered as covariates in the mixed
models. ESA dose was estimated on the log scale; results
were back-transformed to the native scale.
All models were run to three specifications: unadjusted
for any covariate, adjusted for potential confounders that

International Journal of Nephrology and Renovascular Disease 2014:7

Reduced incidence of CRBSI with Tego connector use

were imbalanced between exposure groups (age, race,
vintage, etiology of ESRD; model 1), and adjusted for all
potential confounders considered (model 2). All data wereanalyzed using Stata 10.0 MP (StataCorp, College Station,
TX, USA).

Results
Of 17,175 patients identified who met all inclusion criteria
for the study, 29 patients who were ,18 years old and one
patient for whom information on sex was missing were
excluded, leaving an analytical cohort of 17,145 patients.
Of these, 10,652 patients (62.13%) were classified as Tegocatheter connecter users, and 6,493 patients (37.87%) wereclassified as conventional catheter cap users.

Patient characteristics
Demographic information for the Tego and control cohorts
at the time of first qualifying catheter placement in the
study time frame is provided in Table 1. The mean age ofTego patients was 61.7 years, and the mean age of control
patients was 61.3 years. Tego patients were more likely to be
Hispanic (17.5% versus 13.3%) and less likely to be Black(31.6% versus 33.5%) than controls. Differences between
the cohorts in dialysis vintage and etiology of ESRD wereobserved: a higher proportion of Tego patients were new todialysis (47.7% for Tego versus 41.9% for controls) and a lower
proportion of Tego patients had been on dialysis for more than
12 months (32.4% versus 37.6%), while Tego patients weremore likely to have ESRD attributed to hypertension (28.3%
versus 26.3%) and less likely to have ESRD attributed to diabetes or other causes (44.9% and 26.8% for Tego versus 45.9% and27.8% for controls, respectively). There was no significant sex
imbalance between Tego patients and controls (46.0% female
for Tego patients versus 46.1% for controls) and there were no
meaningful differences in Charlson Comorbidity Index score,a composite score that reflects the number and severity ofcomorbid conditions and which has been shown to predictpatient 10-year mortality,15 or the presence of specific comorbid conditions.

CRBSIsThree metrics of CRBSIs were assessed: IV antibiotic starts,
IV antibiotic courses (defined as receipt of two or moredoses of IV antibiotics within a 21-day period), and positive
blood cultures. The number of events, crude rates, and IRRs
for each are reported in Table 2, and IRRs are represented
graphically in Figure 1A.

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Brunelli et al

Table 1 Demographic comparisons for Tego and control cohorts

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Control(n=6,493)
Age, years Mean ± SD
61.3±15.2
Median (IQR)
62 (51–73)
Minimum–maximum
18–99
Sex
 Male3,501 (53.9%)
Female2,992 (46.1%)
Race/ethnicity White2,938 (45.3%)
Black2,178 (33.5%)
Hispanic
865 (13.3%)
Other
512 (7.9%)
Dialysis vintage, months 02,723 (41.9%)
1–12
1,037 (16.0%).122,441 (37.6%)
Unknown
292 (4.5%)
Primary cause of ESRD
 Hypertension
1,710 (26.3%)
Diabetes
2,981 (45.9%)
Other/unknown
1,802 (27.8%)
Diabetes
4,384 (67.5%)
Heart failure
1,285 (19.8%)
Ischemic heart disease1,184 (18.2%)
Cerebrovascular disease
173 (2.7%)
Peripheral vascular disease
376 (5.8%)
Cardiac dysrhythmia
451 (7.0%)
COPD
602 (9.3%)
Liver disease
123 (1.9%)
Malignancy
247 (3.8%)
Charlson Comorbidity Index15 2495 (7.6%)
3486 (7.5%)
4931 (14.3%)
51,156 (17.8%)
61,201 (18.5%)
7991 (15.3%)
8+1,233 (19.0%)

Tego(n=10,652)

P-value0.1161.7±15.2
63 (52–73)
18–1000.93
5,751 (54.0%)
4,901 (46.0%),0.001
4,602 (43.2%)
3,365 (31.6%)
1,865 (17.5%)
820 (7.7%),0.001
5,077 (47.7%)
1,657 (15.6%)
3,449 (32.4%)
469 (4.4%)
0.02
3,012 (28.3%)
4,785 (44.9%)
2,855 (26.8%)
7,202 (67.6%)
2,104 (19.8%)
2,006 (18.8%)
266 (2.5%)
596 (5.6%)
800 (7.5%)
949 (8.9%)236 (2.2%)
417 (3.9%)

0.90
0.95
0.33
0.50
0.59
0.17
0.42
0.15
0.72
0.34

747 (7.0%)
833 (7.8%)
1,466 (13.8%)
1,825 (17.1%)
2,062 (19.4%)
1,653 (15.5%)
2,066 (19.4%)

Note: Tego needlefree connector is manufactured by ICU Medical, Inc., San
Clemente, CA, USA.
Abbreviations: COPD, chronic obstructive pulmonary disease; ESRD, end-stage
renal disease; IQR, interquartile range; SD, standard deviation.

Among controls, 2,225 IV antibiotic starts were identified
in 1,694 patient-years at-risk time, and among Tego users,
3,308 IV antibiotic starts were identified in 2,811 patientyears at-risk time; this corresponded to crude rates of 131 and118 events per 100-patient years for control and Tego patients,
respectively. Tego use was associated with a 10% relative
reduction in risk of IV antibiotic start (IRR 0.90, 95% confidence interval [CI] 0.85–0.95; P,0.001). In a model adjusting for potential confounders that were imbalanced between
exposure groups (model 1: adjusted for age, race, vintage,

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Table 2 Comparison of catheter-related bloodstream infectionsin Tego and control cohorts
Control(n=6,493)

Tego(n=10,652)

IV antibiotic starts At-risk time, patient- 1,694
2,811
years
 Events
2,225
3,308
 Crude rate (95% CI), 131 (126–137) 118 (114–122)
events per
100 patient-years Crude IRR (95% CI)
1 (ref)0.90 (0.85–0.95) Model 1: adjusted
1 (ref)0.92 (0.87–0.97)
IRR (95% CI) Model 2: adjusted
1 (ref)0.92 (0.87–0.97)
IRR (95% CI)
IV antibiotic course (2+ doses within 21-day period) At-risk time,
1,694
2,811
patient-years Events
1,730
2,499
 Crude rate (95% CI), 102 (97–107)
89 (85–92)
events per
100 patient-years Crude IRR (95% CI)
1 (ref)0.87 (0.82–0.93) Model 1: adjusted
1 (ref)0.89 (0.84–0.95)
IRR (95% CI) Model 2: adjusted
1 (ref)0.89 (0.84–0.95)
IRR (95% CI)
Positive blood culture At-risk time,
1,694
2,811
patient-years Events526
828 Crude rate (95% CI), 31 (28–34)
30 (28–32)
events per
100 patient-years Crude IRR (95% CI)
1 (ref)0.95 (0.85–1.06) Model 1: adjusted
1 (ref)0.98 (0.88–1.09)
IRR (95% CI) Model 2: adjusted
1 (ref)0.98 (0.88–1.09)
IRR (95% CI)

P-value,0.001
0.002
0.002,0.001,0.001,0.001

0.34
0.72
0.71

Notes: Model 1 adjusted for age, race, vintage, and etiology in end-stage renal
disease; Model 2 adjusted for all variables (age, sex, race, vintage, primary causeof ESRD, diabetes, heart failure, ischemic disease, cerebrovascular disease, cardiac
dysrythmia, COPD, liver disease, malignancy, and Charlson comorbidity index).
Tego needlefree connector is manufactured by ICU Medical, Inc., San Clemente,
CA, USA.
Abbreviations: CI, confidence interval; IRR, incidence-rate ratio; IV, intravenous;
ref, reference.

and etiology of ESRD) the protective association of Tego wasslightly attenuated to relative reduction of 8% (IRR 0.92, 95%
CI 0.87–0.97), but was still statistically ­significant (P=0.02).
A fully adjusted model (model 2: adjusted for all covariates
presented in Table 1) yielded estimates identical to those formodel 1. Tego use was also associated with reduced risk of
CRBSI, as assessed by receipt of an antibiotic course (unadjusted IRR 0.87, 95% CI 0.82–0.93; P,0.001). Adjusting forcovariates gave an IRR for Tego versus controls of 0.89 (95%
CI 0.84–0.95, P,0.001) for both model 1 and model 2.

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Reduced incidence of CRBSI with Tego connector use

A

IV antibiotic startInternational Journal of Nephrology and Renovascular Disease downloaded from https://www.dovepress.com/ by 24.131.130.160 on 26-Sep-2020
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Crude
Model 1Model 2

IV antibiotic course
Crude
Model 1Model 2

Positive blood culture
Crude
Model 1Model 2
0.8

0.9

1.0

1.1

1.2

Incidence rate ratio
B

Mortality
Crude
Model 1Model 2

Missed treatments
Crude
Model 1Model 2
0.75

1.00

1.25

Incidence rate ratio
Figure 1 Associations between Tego use and catheter-related bloodstream infection (CRBSI), mortality, and missed dialysis treatments. Incidence-rate ratios (IRRs) with
95% confidence intervals are shown for (A) metrics of CRBSI and (B) mortality and missed dialysis treatments. IRRs for Tego versus controls are shown unadjusted (crude);adjusted for age, race, vintage, and etiology of ESRD (model 1); model 2 adjusted for all variables (age, sex, race, vintage, primary cause of ESRD, diabetes, heart failure,ischemic disease, cerebrovascular disease, cardiac dysrythmia, COPD, liver disease, malignancy, and Charlson comorbidity index).
Note: Tego needlefree connector is manufactured by ICU Medical, Inc., San Clemente, CA, USA.
Abbreviations: IV, intravenous; ESRD, end-stage renal disease.

The unadjusted rate of positive blood cultures was
30 per 100 patient-years for Tego patients and 31 per
100 ­patient-years for controls. The unadjusted IRR for
Tego patients versus controls was 0.95 (95% CI 0.85–1.06,
P=0.34); adjusted models showed no statistically significant
differences between the cohorts.

cohort, 486 deaths occurred over 2,719 patient-years
at-risk time, corresponding to a crude mortality rate of
17.9 deaths per 100 patient-years. There was no significant­association between Tego use and mortality rate observed
on either unadjusted or adjusted analysis (Table 3 andFigure 1B).

Mortality

Missed dialysis sessions

In the control cohort, 283 deaths occurred over 1,639 patientyears at-risk time, corresponding to a crude mortality
rate of 17.3 deaths per 100 patient-years. In the Tego

Tego patients missed fewer dialysis sessions than controls(17.2 versus 17.8 missed sessions per 100 patient-years).
The unadjusted IRR for missed treatments (Tego patientsInternational Journal of Nephrology and Renovascular Disease 2014:7

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Table 3 Comparison of mortality rates in Tego and control
cohorts

At-risk time, pt-years
Deaths
Crude mortality rate
(95% CI), deaths per
100 pt-years
Crude IRR (95% CI)
Model 1: adjusted
IRR (95% CI)
Model 2: adjusted
IRR (95% CI)

Control(n=6,493)

Tego(n=10,652)

1,639
283
17.3 (15.3–19.4)

2,719
486
17.9 (16.3–19.5)

1 (ref)1 (ref)1.04 (0.89–1.20)
1.03 (0.89–1.19)

0.64
0.71

1 (ref)1.02 (0.88–1.19)

0.74

P-value

Notes: Model 1 adjusted for age, race, vintage and etiology in end-stage renal
disease; model 2 adjusted for all variables (age, sex, race, vintage, primary causeof ESRD, diabetes, heart failure, ischemic disease, cerebrovascular disease, cardiac
dysrythmia, COPD, liver disease, malignancy, and Charlson comorbidity index).
Tego needlefree connector is manufactured by ICU Medical, Inc., San Clemente,
CA, USA.
Abbreviations: CI, confidence interval; IRR, incidence-rate ratio; pt, patient;ref, reference.

r­ elative to controls) was 0.97 (95% CI 0.95–0.98; Table 4 andFigure 1B). In fully adjusted analyses, differences wereattenuated, but remained statistically significant (model 2,
IRR 0.98, P=0.04).

Medication use
Figure 2 shows the probability of patients receiving ESAs
and the per-session ESA dose among users for each cohort ineach month of the study: Figure 2A and C present unadjusted
estimates, and Figure 2B and D show adjusted estimates(model 1: adjusted for age, race, vintage, and etiology ofTable 4 Comparison of missed dialysis treatments in Tego andcontrol cohorts

At-risk time, pt-years
Missed treatments
Crude missed-treatment
rate (95% CI), missed
treatments per
100 pt-years
Crude IRR (95% CI)
Model 1: adjusted
IRR (95% CI)
Model 2: adjusted
IRR (95% CI)

Control(n=6,493)

Tego(n=10,652)

1,639
29,15317.8 (17.6–18.0)

2,719
46,74917.2 (17.0–17.4)

1 (ref)1 (ref)0.97 (0.95–0.98)
0.99 (0.97–1.00),0.0010.11

1 (ref)0.98 (0.97–1.00)

0.04

P-value

Notes: Model 1 adjusted for age, race, vintage and etiology in end-stage renal disease;model 2 adjusted for all variables (age, sex, race, vintage, primary cause of ESRD,
diabetes, heart failure, ischemic disease, cerebrovascular disease, cardiac dysrythmia,
COPD, liver disease, malignancy, and Charlson comorbidity index). Tego needlefreeconnector is manufactured by ICU Medical, Inc., San Clemente, CA, USA.
Abbreviations: CI, confidence interval; IRR, incidence-rate ratio; pt, patient;ref, reference.

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ESRD). Both the probability of receiving ESAs and the persession dose declined over the course of the study for bothgroups. The adjusted probability of receiving ESAs was similar between the two groups at all times, except in months 4(adjusted model only) and 6 (unadjusted and adjusted models), where use among Tego patients was modestly higher.
Mean per-session ESA doses for the Tego and control cohorts
declined month on month until month 6. Thereafter, while
the decline in per-session dose continued for Tego patients,
the per-session dose began to increase for control patients,
resulting in statistically significant differences between thecohorts being observed in months 7 (P=0.02), 8 (P,0.001),
and 9 (P=0.009).
The unadjusted per-month probability of receiving thrombolytic treatment was 6.2% for control patients compared to
5.6% for Tego patients (P=0.007; Figure 2E). Adjusting forpotential confounders (age, race, vintage, etiology of ESRD)
yielded similar results (6.3% versus 5.6% for controls versus
Tego, P=0.03).

Discussion
In this retrospective analysis of 17,145 patients receiving incenter HD, Tego connector use was found to be independently
associated with a 10%–12% reduction in risk of CRBSIs, as
defined by initiation of IV antibiotics or initiation of an IV
antibiotic course. A directionally similar, although not statistically significant, association was observed when CRBSIs were
defined by positive blood culture. It should be noted, however,that the lack of statistical significance for this indicator of
infection may be due at least in part to a paucity of identified
events: many patients receive blood cultures in the context of
hospitalization or emergency care, and such cultures were notcaptured in the data assessed. The fact that similar reductionsin the risk of CRBSI were identified using all three definitions
suggests that the observed associations were unlikely due tochance or to choice of definition of infection.
A previously published quality improvement initiative
involving a small number of pediatric HD patients also
demonstrated a decrease in catheter infections upon switching to Tego connectors locked with heparin,14 while a more
recent randomized controlled trial in 66 adult HD patients at asingle center showed no difference in incidence of bacteremia
with Tego connectors locked with saline compared to citratelocked standard catheter caps.13 These studies are limited,
however, by their small size, and were likely underpowered.
The current analysis represents, to our knowledge, the firstlarge-scale evaluation of the Tego connector in a real-world
HD population.

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Reduced incidence of CRBSI with Tego connector use

Control (unadjusted)
Tego (unadjusted)

90

*

80
70
60
50

*P<0.05
0

1

2

3

4

5

6

7

8

100

Probability of receiving ESA

Probability of receiving ESA

B
100

Control (adjusted)
Tego (adjusted)

90
*

*

80
70
60
*P<0.05
50

9

0

1

2

3

Month

4

5

6

7

8

9

Month

C

D
Control (unadjusted)
Tego (unadjusted)

6,000
5,500

*

5,000

*

4,500

*

*

*P<0.05

6,500

Mean per administration
ESA dose (units)

6,500

Mean per administration
ESA dose (units)

Control (adjusted)
Tego (adjusted)

6,000

*

5,500

*

*

*

7

8

9

5,000
4,500

*P<0.05

4,000

4,000
0

1

2

3

4

5

6

7

8

9

0

1

2

Month

E
Per-month probability ofthrombolytic use

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A

3

4

5

6

Month

10%

ControlTego

8%
P<0.05

P<0.05

Unadjusted

Adjusted

6%
4%
2%
0%

Figure 2 (A–E) Medication utilization for Tego and control cohorts. The probability of receiving an erythropoiesis-stimulating agent (ESA) and the per-session ESA doseamong users for Tego and control patients in each month of the study are shown. (A and C) Unadjusted estimates; (B and D) estimates adjusted for age, race, vintage, andetiology of end-stage renal disease (model 1). Unadjusted and adjusted (model 1) estimates of the per-month probability of thrombolytic use over the entire study period
are shown in panel E.
Notes: *Months in which the difference between Tego and control groups was statistically significant (P,0.05). Tego needlefree connector is manufactured by ICU Medical,
Inc., San Clemente, CA, USA.

Beyond the association with reduced incidence of ­CRBSIs,
Tego use was found to be independently associated with adecreased rate of missed dialysis treatments, corresponding
to approximately 0.6 fewer missed treatments per patient
per year. Patients who frequently miss dialysis sessions havehigher rates of morbidity and mortality than those who attend
according to their prescribed schedule, and thus a reductionin the number of missed sessions may have clinical benefits.
Moreover, even a small reduction in the frequency of missed
treatments provides cost benefits to dialysis providers.
Unlike conventional catheter caps, the Tego connector canbe flushed and locked with saline, reducing the need for heparin or other antithrombotic locking solutions.12,13 A potential

International Journal of Nephrology and Renovascular Disease 2014:7

concern, however, is that use of the Tego connector locked withsaline may lead to increased risk of catheter occlusions. Ourdata do not support this hypothesis, and point estimates showthat thrombolytic use (a marker of thrombotic complications)was modestly decreased with Tego use, although it should be
noted that thrombolytic usage overall was very low. Moreover,
it is important to note that we lacked data on interventional
procedures (eg, catheter exchanges), and therefore cannot
make definitive conclusions about relative performance withrespect to mechanical catheter complications.
There was a downward trend in ESA use over the study forboth Tego and control patients. This is perhaps to be expected,
as it has been reported that ESA doses are highest in incident

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Brunelli et alpatients (with a peak at 2 months after onset of dialysis), declining over time as hemoglobin levels normalize,1 and 40%–50%
of patients in this study were new to dialysis at the study
start. In addition to the overall downward trend, Tego use wasassociated with lower ESA utilization compared to controls inmonths 7–9 following catheter placement. Per-administrationdose differences of approximately 500 Units were observed atlater time points in the study, which could have a substantive
financial impact for dialysis providers, particularly in the lightof the recent rebasing of Centers for Medicare and Medicaid
Services reimbursement rates for dialysis.16
One plausible hypothesis is that ESA requirements might
be lower among Tego patients by virtue of lower catheter
infection/colonization burden. The delayed separation in
ESA utilization may reflect the obligate time needed forsufficient numbers of patients to develop ­meaningful levelsof bacterial colonization, as well as response time in titrating ESAs. Considered alongside antibiotic data, we interpretthese data to enrich our inference on vascular-related infections (both overt and ­subclinical). No significant association
between Tego use and mortality was observed. However, we
acknowledge that given the relatively short duration of thestudy, follow-up may not have been long enough to meaningfully assess mortality risk.
As for all observational studies, only associations between
exposure and outcomes could be assessed; a randomized trial
would be needed to demonstrate causality. Although models
were adjusted for covariates that differed between the control
and Tego cohorts, the possibility of residual confounders
cannot be excluded.
Infectious complications due to chronic catheter use in HD
patients who are not good candidates for arteriovenous fistulas
or arteriovenous grafts are an ongoing concern. Our findings
suggest that the use of the Tego connector may reduce the riskof CRBSIs, and in addition may result in lower utilization ofthrombolytics, antibiotics, and ESAs, as well as fewer missed
dialysis treatments; however, a randomized controlled trial
would be needed to confirm these findings. Budget impact
models accounting for all of these factors, as well as the costof the device itself, will be required to quantify the potential
cost benefit of the Tego connector to payers.

Acknowledgment
We thank DaVita Clinical Research® (DCR®) for providing technical support for this research project. DCR iscommitted to advancing the knowledge and practice ofkidney care.

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DisclosureThis study was supported by ICU Medical, Inc. SMB is an
employee of DCR, and has served on advisory boards for
Keryx Biopharmaceuticals, Otsuka Pharmaceutical, Amgen,
and CB Fleet; SMB’s spouse is employed by AstraZeneca.
LN is an employee of DaVita HealthCare Partners, Inc. AEH
is an employee of DCR. SPS is an employee of DCR, andowns stock in DaVita HealthCare Partners, Inc.

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