Nephrol Dial Transplant (2017) 32: 685–692

doi: 10.1093/ndt/gfw044
Advance Access publication 7 April 2016

Original Articles

Clinical safety and performance of VIVIA: a novel home

hemodialysis system
Angelito A. Bernardo1*, Thomas C. Marbury2, Phil A. McFarlane3, Robert P. Pauly4, Michael Amdahl1,

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Jason Demers5, Audrey M. Hutchcraft1, John K. Leypoldt1, Mark Minkus1, Matt Muller1, Ruth Stallard1 and
Bruce F. Culleton1
1
Baxter Healthcare Corporation (DF5-1N), One Baxter Parkway, Deerfield and Round Lake, IL 60015, USA, 2Orlando Clinical Research Center,
Orlando, FL, USA, 3St. Michael’s Hospital, Toronto, ON, Canada, 4University of Alberta Hospital, Edmonton, AB, Canada and 5DEKA Research
& Development Corporation, Manchester, NH, USA

*Correspondence and offprint requests to: Angelito Bernardo; E-mail: angelito_bernardo@baxter.com

Conclusion: These results confirm the safety and expected per-

ABSTRACT ||
|| formance of VIVIA.
||
Background: The VIVIA Hemodialysis System (Baxter || Keywords: dialysate for infusion, extended use, heat disinfec-
|| tion, home hemodialysis, VIVIA
Healthcare Corporation, Deerfield, IL, USA) was designed for ||
patient use at home to reduce the burden of treatment and ||
||
improve patient safety. It has unique features including ||
extended use of the dialyzer and blood set through in situ hot- || INTRODUCTION
||
water disinfection between treatments; generation of on-line ||
infusible-quality dialysate for automated priming, rinseback || The economic and personal patient burden associated with
||
and hemodynamic support during hypotension and a fully inte- || treating end-stage renal disease (ESRD) in North America and
grated access disconnect sensor. || around the world is staggering. As of 2010, there were an esti-
||
Methods: The safety and performance of VIVIA were || mated 2.618 million patients worldwide on renal replacement
assessed in two clinical studies. A first-in-man study was a pro- || therapy (RRT), a number that was projected to double to 5.439
||
spective, single-arm study that involved 22 prevalent hemodial- || million by 2030 [1]. As of 2011, the US Renal Data System
ysis (HD) patients who were treated for 4 h, four times a || (USRDS) Annual Report [2] noted 616 000 patients received
||
week, for 10 weeks. A second clinical study was a prospective, || treatment in the USA for ESRD, and of these >430 000 preva-
single-arm study (6–8 h of dialysis treatment at night three || lent patients, 92% received in-center hemodialysis (HD).
||
times a week) that involved 17 prevalent patients treated for 6 || Moreover, the cost to treat Medicare patients with ESRD in the
weeks. || USA in 2011 was $34.3 billion [2]. Registry data from 30 coun-
||
Results: There were 1114 treatments from the two studies (first- || tries and regions in Europe reporting to European Renal
in-man study, 816; extended duration study, 298). Adverse || Association-European Dialysis and Transplant Association
||
events (AEs) were similar in the two studies to those expected || (ERA-EDTA) indicated that there were 69 000 incident and 451
for prevalent HD patients. No deaths and no device-related seri-
|| 000 prevalent patients on RRT in 2012, although this is an
||
ous AEs occurred. Adequacy of dialysis (Kt/V)urea in both clini- || underestimate, as a number of countries, including Germany,
cal trials was well above the clinical guidelines. VIVIA per-
|| Poland and Italy, do not report data to the ERA-EDTA [3].
||
formed ultrafiltration accurately as prescribed in the two || Expanding scientific evidence indicates that clinical out-
studies. The majority of patients achieved 10 or more uses of the
|| comes of suitable HD patients can be improved with more fre-
||
dialyzer. Endotoxin levels and bacterial dialysate sampling met || quent and/or longer duration than conventional thrice-weekly
infusible-quality dialysate standards.
|| HD [4, 5]. Frequent and/or longer-duration HD results in lower
||
| fluctuations in serum electrolytes and extracellular fluid

C The Author 2016. Published by Oxford University Press

V 685
on behalf of ERA-EDTA. All rights reserved.
volumes, lower ultrafiltration rates and higher clearance of ure- ||
mic toxins. Indeed, patients treated with high-dose HD thera- ||
pies have lower blood pressure [6–8], improved serum ||
||
phosphorus levels [6, 7, 9], regression of left ventricular mass [6, ||
7, 10] and improved quality of life [6, 7]. In an observational ||
||
study, 177 patients on frequent nocturnal home HD had 5-year ||
survival of 85%, similar to survival rates in a matched cadaveric
||
||
renal transplant cohort [11]. ||
A substantial barrier to widespread use of high-dose HD
||
||
therapies is the inability of dialysis centers to accommodate fre- ||
quent or long-duration HD. Among many other barriers to
||
||
growth of high-dose home HD is the absence of a smaller, ||
patient-friendly home HD system that delivers high-dose HD
||
||
[5, 12]. Devices should mitigate inherent risks associated with ||
||
HD and permit easy and time-saving set up and take down, ||
thus reducing the burden for the patient and care partner. ||
||
This report describes the first clinical evaluation of a novel ||
home HD system, VIVIA (Baxter Healthcare Corporation,
Deerfield, IL, USA). The two studies discussed herein were per-
formed to evaluate the safety and performance of VIVIA in an
in-center environment prior to patient use in the home setting.
MATERIALS AND METHODS
VIVIA hemodialysis system
VIVIA includes the VIVIA Treatment Device and the
VIVIA Water Device (Figure 1). The VIVIA Treatment Device
consists of the patient module (including the VIVIA Dialysate
Set and Ultrafilter, the VIVIA Blood Set, the VIVIA Dialyzer,
VIVIA Acid and VIVIA Bicarb), the pump module that pro-
vides pneumatic pressure to maintain the flow of blood and
dialysate and the touchscreen module that serves as the user
interface to guide the user from treatment setup through to
completion. The VIVIA Treatment Device also generates dialy-
sate, as well as monitors and controls blood and dialysate
pathways.
In comparison with conventional HD machines, the VIVIA
Treatment Device has a pneumatically controlled diaphrag-
matic pump. The VIVIA blood flow can be set up to 400
mL/min, in contrast to a setting of up to 650 mL/min in
FIGURE 1: Features of the VIVIA Hemodialysis System treatment device.
686
conventional machines. The dialysate flow of conventional
devices reaches up to 1000 mL/min, while the VIVIA
Treatment Device delivers up to 400 mL/min. VIVIA has been
validated to generate in situ dialysate for infusion (for priming,
bolus administration and rinseback), avoiding the extra steps
needed to set up and use saline bags in conventional devices.
Anticoagulant delivery in VIVIA is done through an integrated
heparin delivery system in which a new 30 mL (1000 unit/mL)
heparin vial is directly installed and seated into the heparin
port. This eliminates the need for transfer of heparin to a
syringe from a concentrated heparin bottle, dilution in a saline
bag and transfer into a syringe that is then installed into a
machine syringe pump. For ease of use, VIVIA features
extended use of the blood set and dialyzer compared with the
single-use requirements for conventional devices. Extended use
is achieved through automated in situ nonchemical hot-water
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disinfection of the blood set and dialyzer. Prior to each treat-
|| ment, VIVIA performs an automated clearance test of the dia-
||
|| lyzer, alerting the user to replace the dialyzer if necessary. An
|| access disconnect sensor is integrated in VIVIA, a feature not
||
|| found in other HD devices.
|| VIVIA has built-in protective systems and alarms to ensure
||
|| safety. Dialysate solution composition is monitored through
|| redundant conductivity cells in the dialysate flow path, with
||
|| specific alarm set points. Thermistor measurements of the dial-
|| ysate temperature are done at different points in the device.
||
|| Volumetric control, adjustment and monitoring of the ultrafil-
|| tration rate are regulated closely. Blood leak in the dialyzer is
||
|| detected by photometric sensors, whereas blood leak to the
|| environment is monitored by fluid leak sensors. Arterial and
||
|| venous pressures are tightly controlled and measured continu-
|| ously during treatment. The VIVIA access disconnect sensor,
||
|| integrated into the blood tubing set, is automatically activated
|| when the patient connects at the start of treatment. When a dis-
||
|| connect in the blood circuit is detected, VIVIA sounds an alarm,
|| the blood pumps stop and the system goes into safe mode. As
||
|| noted above, VIVIA monitors the clearance of the dialyzer at
|| each treatment and alerts the patient when to change the
||
|| dialyzer.
|| The VIVIA Dialyzer is a high-flux polyethersulfone dialyzer
||
|| with a surface area of 2.1 m2. The VIVIA Dialyzer and VIVIA
A.A. Bernardo et al.
Blood Set are validated for multiple use by undergoing in situ ||
automated hot-water disinfection (85 C for 1 h) between treat- ||
ments. The VIVIA Treatment Device produces dialysate for
||
||
infusion into the patient during priming, rinseback and for vol- ||
ume expansion during hypotension instead of using saline.
||
||
The VIVIA Water Device is designed to supply ultrapure ||
water (via reverse osmosis and electronic deionization) to the
||
||
VIVIA Treatment Device to generate dialysate flow rates of up ||
||
to 400 mL/min; however, the Water Device was not used ||
because it was not available at the time of the study. Instead, the
Millenium HX Water Portable Dialysis Water System (Mar
Cor, Plymouth, MN, USA) was used to produce dialysis water
purified by reverse osmosis during these studies. Importantly,
the quality of the dialysis water produced by this portable device
meets minimum Association for the Advancement of Medical
Instrumentation/International Organization for
on the practice in the dialysis clinic. The clinician adjusted the
heparin dose during the stabilization period based on the acti-
vated partial thromboplastin time (aPTT), with the goal
of achieving aPTT ratio between 1.5 and 2.5 times baseline
[13, 14].
A new blood set and dialyzer were used at the beginning of
the evaluable period. Before each treatment, dialyzer sodium
clearance was measured by the VIVIA Treatment Device and
the dialyzer and blood set were reused unless the dialyzer
|| sodium clearance was 90% of the dialyzer initial measure-
||
|| ment, there were functional defects of the dialyzer or blood set
|| (leaks, tubing separations) or there were physical appearance
||
|| abnormalities (such as significant blood clots or biomaterial)
|| present.
||
|| All adverse events (AEs) were collected starting from the
|| time the patient signed the informed consent until the end of
||

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Standardization (AAMI/ISO) water quality standards for || the study. An AE was considered serious if it resulted in death,
dialysis. || hospitalization, prolongation of hospitalization or if it was an
||
Both studies were conducted in accordance with the princi- || important medical event that required an intervention to pre-
ples and guidelines set forth in the Declaration of Helsinki and || vent a death or hospitalization. An AE was considered micro-
||
the International Conference on Harmonisation Guidelines for || biologically related if it was accompanied by fever, rigors or
Good Clinical Practice. Written informed consent was obtained || sepsis during or within 4 h after an HD treatment.
||
from every patient prior to participation in any research || VIVIA Treatment Device performance was determined by
activity. || assessing dialysis dose and ultrafiltration. Dialysis dose was cal-
||
|| culated as weekly standard urea Kt/V (stdKt/V) from spKt/V
First-in-man clinical study || determined weekly on a Wednesday (preceded by a nontreat-
||
This was a prospective, open-label, single-arm, nonrandom- || ment day) [15–17]. Urea spKt/V was calculated from predialysis
|| and postdialysis serum urea nitrogen concentrations using the
ized study designed to assess the safety and performance of the ||
VIVIA Treatment Device in a supervised setting by trained clin- || second-generation Daugirdas equation [15] then converted to
|| weekly stdKt/V values [17]. Blood samples were taken before
ical staff. The study consisted of a 2-week screening period and ||
a 10-week treatment period. Briefly, male and female patients || and after dialysis as per Kidney Disease Outcomes Quality
|| Initiative (KDQOI) guidelines [18] and processed at a central
18 years old were eligible if they were on chronic thrice- ||
weekly HD for the last 90 days and achieved a single-pool urea || laboratory (SGS Life Sciences Services, Lincolnshire, IL, USA).
|| Ultrafiltration was assessed for each HD treatment and was
Kt/V (spKt/V) 1.2 (or an equivalent urea reduction ratio of ||
0.65 or an equilibrated urea Kt/V 1.0 or a weekly standar- || summarized for the 8-week evaluable period. Fluid weight
|| removed was calculated as the total ultrafiltration removed (as
dized Kt/V 2.0) on two occasions within 60 days of enroll- ||
ment. Exclusion criteria were a history of noncompliance with || recorded by the VIVIA Treatment Device), corrected for the
|| priming and rinseback volumes (as recorded by the VIVIA
dialysis therapies, prescheduled living donor kidney transplant ||
within the next 6 months or a severe comorbidity with a life || Treatment Device) and total oral intake and total output (such
||
expectancy of <1 year. Patients with known allergic reactions to || as emesis and urine). Patient weight was measured before and
PUREMA polyethersulfone were also excluded. || after each HD treatment using a calibrated digital scale to deter-
||
During the first 2 weeks, patients were stabilized on their || mine ‘weight change’.
new dialysis prescription. The last 8 weeks of the treatment || Samples (from the venous line) for assessing dialysate quality
||
period were used to evaluate the performance of the VIVIA || were taken at the beginning of the 10-week treatment period,
Treatment Device (evaluable period); however, safety data were || after each dialyzer replacement, at a minimum every week, and
||
collected during the entire 10-week treatment period. || at the end of the 10-week treatment period. All dialysate sam-
All treatments in this study were performed at two study
|| ples were assayed for bacteria and endotoxin levels based on a
||
sites in the USA (Orlando Clinical Research Center, Orlando, || standard [19] at the central laboratory.
FL and DaVita Clinical Research, Minneapolis, MN, USA).
||
||
Patients were treated for up to 4 h on Monday, Wednesday, ||
Thursday (or Friday) and Saturday. Blood flow rate and treat-
|| Extended duration clinical study
||
ment time could be adjusted during the first 2 weeks of the || A second prospective, open-label, single-arm, nonrandom-
||
treatment period, but these parameters were not changed dur- || ized study assessed the VIVIA Treatment Device during
ing the evaluable period to mitigate the influence of these factors || extended-duration treatments (>6 h/treatment) in Canada (St.
||
on the performance assessment of the VIVIA Dialyzer with || Michaels’ Hospital, Toronto, Ontario, Canada and Edmonton
multiple use. Heparin administration was individualized to ||| General Hospital, Alberta, Canada). All patient treatments were
inhibit extracorporeal circuit clotting or fibrin formation yet || performed in-center by trained clinical staff at night. Eligibility
||
minimize postdialysis bleeding. Initial heparin dosing was based criteria were similar to those used in the first study, except that

SafetyandperformanceofVIVIA 687
patients were eligible if they were on nocturnal HD thrice
||
weekly for at least 30 days prior to entry into this study. ||
The study consisted of a 2-week screening period and a 6- ||
||
week treatment period where patients were treated thrice ||
weekly for 6–8 h/treatment. The first week of the treatment ||
||
period was used to stabilize patients on their new prescriptions. ||
The performance of the VIVIA Treatment Device was assessed ||
||
during the last 5 weeks (evaluable period). ||
A new blood set and dialyzer were used at the beginning of ||
||
the 5-week evaluable period and the conditions for the multiple
use of the dialyzer were similar to those used in the first-in-man
study. Safety data were collected during the entire 6-week treat-
ment period in a manner similar to that employed during the
first study. Definitions for AEs were the same in both studies.
Performance of the VIVIA Treatment Device was also deter-
mined by assessment of dialysis dose and ultrafiltration. In this
man study and 298 in the extended-duration study). Baseline
and in-study treatment parameters for both studies are shown
in Table 2. Heparin dose was determined by measuring the
aPTT ratio. In the first-in-man study, the mean [6 standard
deviation (SD)] aPTT was 2.42 6 0.59 times higher than base-
line after initial heparin infusion and 1.64 6 0.45 higher than
baseline before the end of treatment. In the extended duration
study, the mean (6SD) aPTT was 2.26 6 1.01 times higher
than baseline after initial heparin infusion and 2.42 6 1.32
|| times higher before the end of treatment. Notably, dialysate
|| flow rates were lower during both studies than before study
||
|| entry and the heparin loading dose and total heparin infusion
|| requirements increased from baseline.
||
||
||
|| Safety
||

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study, however, dialysis dose was calculated as the spKt/V deter- || One hundred and three AEs were reported in the first-in-
||
mined at the midweek treatment preceded by 1 nontreatment || man study and 52 AEs were reported in the extended-duration
day using the second-generation Daugirdas equation [15]. || study, for a combined AE rate of 14 events/100 treatments.
||
Ultrafiltration was assessed for each HD treatment. || Intradialytic hypotension was the most common AE in both
Samples for assessing dialysate quality were taken at device || studies (2 occurrences/100 treatments in the first-in-man study
||
installation and before treatments on Days 1, 10 and 18. All || and 5 occurrences/100 treatments in the extended duration
dialysate samples were collected and assayed in a similar man- || study). Ten AEs were considered device related; nine of these
||
ner to that used in the first study. || were blood loss (50–250 mL) and occurred primarily during
|| rinseback or toward the end of an HD treatment. The remain-
||
|| ing device-related AE was hypotension. Six patients experienced
|| a serious AE (anemia, asthma, fractured ankle, hypotension,
RESULTS ||
|| pain in an extremity and arteriovenous fistula thrombosis); all
Twenty-one patients received treatment with the VIVIA
|| of these events resulted in hospitalization, but none were con-
||
Treatment Device during the first-in-man study; 20 of these || sidered related to the VIVIA Treatment Device. No patient
patients completed the 10-week treatment period. Seventeen
|| experienced a microbiologically related AE and no patient died
||
patients were treated during the extended duration study; 16 of || or was withdrawn from the study due to an AE.
||
these patients completed the 6-week treatment period. Baseline ||
characteristics for study patients are shown in Table 1. ||
|| Performance
Combining both studies, 1114 HD treatments were per- ||
formed with the VIVIA Treatment Device (816 in the first-in- || In the first-in-man study, the mean weekly stdKt/V was 2.97
|| [95% confidence interval (CI) 2.84–3.11]. In the extended dura-
||
|| tion study, the mean urea spKt/V was 2.49 (95% CI 2.02–2.96).
Table 1. Baseline patient characteristics and treatment parameters by clini- || Figure 2 shows weekly stdKt/V by week for the first-in-man
cal study ||
||
Characteristic First-in-man Extended duration ||
study (n ¼ 22) study (n ¼ 17)
|| Table 2. Baseline and in-study treatment parameters by clinical study
||
Mean age, years (SD) 50.9 (9.5) 54.9 (14.2)
|| Characteristic First-in-man Extended
|| study duration
Female, n (%) 10 (45.5) 6 (35.3) || (n ¼ 22) study
Mean target dry weight, kg (SD) 80.2 (16.8) 81.7 (17.5) || (n ¼ 17)
Mean time since first dialysis 12.0 (7.4) 9.6 (8.2) ||
treatment, years (SD)
|| Prestudy prescription
||
Race, n (%) || Mean treatment time/session, hours (SD) 3.48 (0.4) 7.3 (0.6)
Black 16 (72.7) 3 (17.6) || Treatment frequency/week, n 3 3
White 5 (22.7) 8 (47.1) || Mean blood flow rate, mL/min (SD) 473 (43) 302 (22)
Native Hawaiian or other 0 3 (17.6)
|| Mean dialysate flow rate, mL/min (SD) 700 (126) 500 (61)
||
Pacific Islander || Mean heparin bolus, units (SD) 2175 (2759) 1324 (683)
Asian 0 1 (5.9) || Mean heparin infusion, units/hour (SD) 815 (882) 935 (453)
Other 1 (4.5) 2 (11.8) || In-study prescription
||
Cause of ESRD, n (%) || Mean treatment time/session, hours (SD) 3.9 (0.2) 7.0 (0.6)
Diabetic nephropathy 4 (18.2) 6 (35.3) || Treatment frequency/week, n 4 3
Hypertension 11 (50.0) 0 (0) || Mean blood flow rate, mL/min (SD) 358 (21) 293 (23)
Glomerulonephritis 2 (9.1) 6 (35.3)
|| Mean dialysate flow rate, mL/min (SD) 395 (9) 318 (27)
||
Polycystic kidney disease 3 (13.6) 0 (0) || Mean heparin bolus, units (SD) 3078 (1106) 1854 (696)
Other 2 (9.1) 5 (29.4) || Mean heparin infusion, units/h (SD) 1061 (510) 1564 (498)
||
ESRD, end-stage renal disease; SD, standard deviation. SD, standard deviation.

688 A.A. Bernardo et al.

 || EU/mL (0.243, 0.0345, 0.035, 0.03 and 0.03 EU/mL). The sam-
|| ple resulting in the 0.243 EU/mL endotoxin measurement was
|| taken when the device was temporarily out of service and asep-
||
|| tic techniques were not required; it is plausible that such han-
|| dling of the device contributed to the elevated endotoxin level.
||
|| Although a review of the other four out-of-range endotoxin val-
|| ues showed that they were valid as defined by the testing proce-
||
|| dure, retesting of all these samples (in quadruplicate) resulted in
||
|| measured values that were consistent at <0.03 EU/mL.
||
|| Extended use of the VIVIA dialyzer
||
|| The number of dialyzers used and the maximum use count
||
|| for patients in both studies are shown in Table 3. A large varia-
|| bility in the number of times a dialyzer could be reused, both
||
|| among and within patients, is evident. In both studies, the
|| majority of patients were able to achieve at least 10 uses from
||

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|| the same VIVIA Dialyzer. The most common reason for dia-
|| lyzer replacement (62% of occurrences in both trials combined)
||
|| was due to the physical appearance of the dialyzer or blood set,
|| usually small amounts of fibrin seen within the venous header
||
|| of the VIVIA Dialyzer or the blood pump pods of the blood set.
|| The amount and frequency of fibrin deposition improved with
||
FIGURE 2: (A) Weekly standard urea Kt/V (stdKt/V) for the last 8
|| optimization of the heparin prescription. Dialyzers were
||
weeks of the treatment period (evaluable period) during the first-in- || replaced in 8% of treatments due to failed in situ tests for dia-
man clinical study. The dashed line indicates an adequate weekly || lyzer sodium clearance.
||
dialysis dose as defined by KDOQI [18]. (B) Single-pool urea Kt/V ||
(spKt/V) for the last 5 weeks of the treatment period (evaluable ||
period) during the extended-duration clinical study. Mean values
||
|| DISCUSSION
and 95% confidence limits are shown. The dashed line indicates an ||
adequate dialysis dose for patients treated thrice weekly as defined by ||
|| The vast majority of HD devices obtain market clearance based
the KDOQI [18]. ||
|| on predicate comparisons. Clinical studies prior to use in ‘real
|| life’ are not required by regulatory bodies. In contrast, VIVIA
study and urea spKt/V by week for the extended duration study || includes unique features that reduce the burden of HD and mit-
||
during each study’s respective evaluable period. || igate inherent risks of HD. Given these differences versus con-
The mean (6SD) ultrafiltration volume for the first-in-man || ventional HD devices, the safety and performance of VIVIA
||
study was 2.77 6 1.26 kg (range 0.4–6.4 kg) and 3.66 6 1.37 || were tested in controlled clinical environments.
kg (range 0.6–7.7 kg) for the extended-duration study [20]. The || The majority of AEs observed in these two clinical studies
||
difference between fluid weight removed (as determined by the || were secondary to underlying comorbidity or the HD therapy
VIVIA Treatment Device) and weight change (as measured by || itself. No AEs related to the infusion of dialysate were observed.
||
a digital calibrated weight scale) is graphically demonstrated in || The majority of device-related AEs were secondary to clotting
Figure 3. The correlation between these two measured parame- || of the extracorporeal blood circuit or incomplete rinseback—
||
ters was strong. The median difference between fluid weight || events known to occur with conventional HD devices when
removed and weight change was 0.20 kg for the first-in-man || anticoagulation is not optimal. Compared with baseline,
||
study and 0.30 kg for the extended duration study, indicating || patients within both clinical studies required an increase in
a small but consistently greater weight change as measured by
|| either the heparin loading dose or infusion rate, or both. aPTTs
||
the scale than fluid removed. || were targeted for 1.5–2.5 times the baseline value for each
|| patient [13, 14]. The increased heparin utilization may have
||
|| been due to more attention given to anticoagulation during the
Dialysate quality || studies and/or the desire to achieve optimal anticoagulation to
||
A total of 630 dialysate samples were collected from VIVIA || maximize use of the same dialyzer and blood set. Despite the
Treatment Devices during these studies. Of these, 626 samples
|| increase in heparin use above baseline, no increase in bleeding
||
(99%) showed no bacterial growth at 72 h. Two samples (first- || events was observed.
||
in-man clinical study) showed bacterial counts of 0.002 CFU/ || The performance of VIVIA was determined by measuring
mL (1 CFU/500 mL sample). These two samples were taken || urea clearance and ultrafiltration accuracy. Urea clearances in
||
from nonpatient devices, and the positive results from root || both studies were well above published clinical guidelines [21,
cause analysis were likely due to contaminated ice that was used ||| 18] and within the expected range. The maximum blood and
to transport the samples. In the extended-duration study, five || dialysate flow rate with VIVIA is 400 mL/min, an intentional
||
endotoxin measurements (0.8%) exceeded the threshold of 0.03 design feature to limit the size of the pneumatic pumps, noise

SafetyandperformanceofVIVIA 689
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FIGURE 3: The Bland–Altman plot of fluid weight removed plotted versus weight change for treatments during (A) the first-in-man clinical
study and (B) the extended-duration clinical study.

generation and water consumption while ensuring efficient sol-
||
ute clearance using a modern high-flux dialyzer. ||
VIVIA also performed ultrafiltration as desired. The correla- ||
||
tion between fluid weight removed and weight change was ||
strong and consistent across both clinical studies. The use of ||
||
digital calibrated scales and measurement of all fluid input and ||
output allowed us to tease out the amount of insensible fluid ||
||
loss during HD treatments [22–24]. Although this varied
among patients, the median insensible fluid loss for mean 4-
and 7-h treatments was 200 and 300 mL, respectively. Given
that each patient’s weight did not change throughout both clini-
cal studies, it is unlikely that insensible fluid loss has any clinical
relevance in the management of HD patients.
The studies demonstrated the feasibility of extended use of
the VIVIA Dialyzer and Blood Set for multiple treatments using
nonchemical in situ hot-water disinfection. The majority of
patients were able to achieve 10 or more uses from the same
VIVIA Dialyzer and Blood Set, a feature that reduces the bur-
den of therapy on the patient and/or care partner. As shown in
Table 3, the variability within and among patients was consider-
able. Extended use of the same dialyzer and blood set was
improved with optimized anticoagulation using the aPTT as a
guide [13, 14].
|| These studies are not without limitations. Control groups
|| were not used in either study. Although clinical studies are not
||
|| required for the majority of HD devices prior to their commer-
|| cial launch, we designed these studies to meet regulatory guid-
||
|| ance. The studies were also performed in in-center settings and
|| not the home environment. Although VIVIA is specifically
||
||| designed for the home, rigorous performance testing is difficult
|| to perform in the home setting, where additional nondevice fac-
|| tors may impact safety and performance. The duration of each

690 A.A. Bernardo et al.

Table 3. The number of dialyzers used and the maximum use count during the first-in-man and extended-duration clinical studies

Patienta First-in-man study Extended-duration study

Treatments Dialyzers Maximum use count Treatments Dialyzers Maximum use count
1 2 2 1 19 3 17
2 35 23 5 15 9 5
3 34 26 4 18 14 3
4 35 4 24 18 7 10
5 33 11 9 18 2 13
6 32 5 23 18 2 17
7 32 6 13 16 8 4
8 32 9 19 18 3 15
9 34 20 8 18 3 10
10 31 7 8 18 3 13
11 32 4 13 17 5 10
12 32 11 9 18 4 12
13 30 26 5 18 5 7
14 31 9 11 17 10 5

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15 34 12 17 17 7 5
16 31 4 24 19 3 11
17 33 8 18 18 5 6
18 33 9 16
19 32 2 20
20 30 5 23
21 31 4 16
a
In the first-in-man clinical study, the first 2 weeks of the study served as a prescription stabilization period and data from this period were not used to assess the extended use of the
VIVIA Dialyzer. Therefore, only 21 patients are included for the first-in-man study.

study was also too short to determine long-term safety and clin-
ical effectiveness. Future studies are planned to gather these || CONFLICT OF INTEREST STATEMENT
||
data. It should also be noted that more accurate formulas for ||
calculating stdKt/V for HD therapies applied more frequently || A.B., M.A., J.K.L., M.M., R.S. and B.C. are full-time employees
|| of Baxter Healthcare Corporation with ownership interests.
than thrice weekly have only recently been published [25, 26]; ||
however, use of such formulas using data from the first-in-man || A.H. was a full-time employee of Baxter Healthcare
|| Corporation at the time of the study. P.M. has been a consul-
clinical study resulted in minor differences that would not alter ||
tant for and received research funding from Baxter
conclusions regarding the ability to achieve an adequate dialysis |||
dose [27]. || Healthcare Corporation.
||
In conclusion, data from these two clinical studies conducted ||
in prevalent HD patients confirm the safety and expected per- ||
||
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Nephrol Dial Transplant (2017) 32: 692–698

doi: 10.1093/ndt/gfw043
Advance Access publication 25 March 2016

Erythropoiesis-stimulating agent dosing, haemoglobin and

ferritin levels in UK haemodialysis patients 2005–13
Kate Birnie1, Fergus Caskey1,2,3, Yoav Ben-Shlomo1, Jonathan A.C. Sterne1, Julie Gilg2, Dorothea Nitsch4
and Charles Tomson5
1
School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol BS8 2PS, UK, 2UK Renal
Registry, Southmead Hospital, Bristol, UK, 3Renal Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK, 4Department of Non-
communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK and 5Department of Renal Medicine,
Freeman Hospital, Newcastle upon Tyne, UK

Correspondence and offprint requests to: Kate Birnie; E-mail kate.birnie@bristol.ac.uk

|| observational studies suggest better outcomes for patients who

ABSTRACT ||
|| achieve higher haemoglobin (Hb) levels, randomized controlled
Background: Erythropoiesis-stimulating agents (ESAs) with ||| trials comparing higher and lower Hb targets have led to safety
intravenous iron supplementation are the main treatment for ||| concerns over higher targets and to changes in treatment
anaemia in patients with chronic kidney disease. Although ||| guidelines.
|

C The Author 2016. Published by Oxford University Press on behalf of ERA-

V
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