A Clinical Study Comparing the Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux Revaclear and Fresenius Optiflux Dialyzers
Phase: NA
Conditions: End Stage Renal Disease (ESRD)
Sponsor: University of Missouri-Columbia

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015
 
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A Clinical Study Comparing the Basic Performance and Blood  
Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Dialyzers 
 
 
 
 
 
 
 
 
Madhukar Misra MD FRCP (UK) FACP FASN 
Professor of Medicine (Nephrology) 
University of Missouri Hospitals and Clinics 
Columbia MO 65212 
And 
Dialysis Clinic Incorporated 
Columbia, MO 65201 
 
 
 
 
 
 
 
 
May 5, 2015 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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Introduction 
 
The dialyzer ELISIO-H is a new high-flux dialyzer made from POLYNEPHRON™ fiber 
designed and manufactured by Nipro Corporation Japan. The dialyzer has already been 
subjected to in-vitro testing, and all legally required biological safety tests have been 
conducted and certified by an external institute. A number of clinical studies have 
already been successfully completed for this membrane mainly in Japan and Europe.  
Nipro ELISIO-H dialyzers are commercially available for several years outside of U.S.A. 
On 20th December 2013, ELISIO-H dialyzer is 510k-approved for its sales in U.S.A.  
 
Evaluation Objective 
 
The aim of the study is to confirm the safety and clinical effectiveness of the Nipro 
ELISIO-H by compare the performance characteristics and hemo-compatibility of Nipro 
ELISIO-H with those of the commercially available dialyzers in U.S.A., Gambro Polyflux 
Revaclear and Fresenius Optiflux.  
 
Clinical Investigator  
 
 
Principal Investigator 
Professor Madukhar Misra 
 
 
Professor Madukhar Misra  
University of Missouri Hospitals and Clinics  
University of Missouri Hospitals and Clinics  
Columbia, MO 65212 
 
 
 
Columbia, MO 65212 
Tel: 573-882-7991  
 
 
 
Tel: 573-882-7991  
Fax: 573-884-4820  
 
 
 
Fax: 573-884-4820  
Email: MisraM@health.missouri.edu  
 
Email: MisraM@health.missouri.edu 
 
Sponsor 
Nipro Medical Corporation 
3150 NW 107 Ave, 
Miami, Florida 33172 
Tel: 305-599-7174 
Fax: 305-592-4621 
 
 
 
 
 
 
 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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Details  
   a) Membrane and Dialyzer Types  
 
Dialyzer 
Labelling 
Membrane 
Dialyzer 
Manufactur
er 
UF Coeff. 
mL/h/mmHg 
Surface 
m2 
Sterilization 
Nipro ELISIO-H 
POLYNEPHRON
™ 
Nipro, Japan 
67.0 
1.5 
Gamma 
Gambro Polyflux 
Revaclear  
PAES  
Gambro 
USA  
60.0 
1.4 
Steam 
Fresenius  
Optiflux 
Polysulfone  
Fresenius,  
USA 
60.0 
1.6 
ETO 
 
   b) Design: 
Study Design: Clinical study according to the US Federal Law that means no necessity of 
the permission of authorities, but because of blood sampling a vote of an ethics committee 
should be procured. 
   c) Patients   
Ten (10) stable patients receiving regular dialysis treatment will be chosen for this 
evaluation. The n of ten was chosen from previous experience with studies of this kind.  
However with the expectation of a 20% drop out rate a total of twelve patients will be 
selected from the patient population meeting the inclusion criteria. Standard hemodialysis 
will be performed with each dialyzer type.  
   d) Patient Inclusion Criteria 
 ESRD patients 18 years or older 
 Stable on hemodialysis for more than 3 months 
 Stable hemoglobin 11 g/dl or greater, see attached DCI erythropoietin 
protocol. 
 Stable AV fistula vascular access 
 Stable anticoagulation and ESA regimen 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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 No active infection 
 Able to sign informed consent and able to participate in the study 
 Medically stable 
   e) Patient Exclusion Criteria 
 Participation in another study which may interfere with the planned study 
 Active infection 
 Medical conditions which may interfere with the study (cardiac, liver disease,   
 Hepatitis) 
 Female who are pregnant or planning to be pregnant 
 Problem with or allergy to anticoagulation 
 Patient cannot tolerate Heparin 
 Allergy to dialyzer material e.g. polysulfone 
    f) Withdrawal Criteria 
 Patients own decision. 
 Relocation, transportation 
 Severe mechanical problems with dialyzers e.g. frequent fiber leakages. 
 Hypertensive reactions e.g. erythema, edema. 
 Non-compliance with therapeutic regimen. 
 Change of anticoagulation scheme. 
 Other serious problems induced by treatment. 
 Any dialysis-related medical problem judged to be sufficiently serious by the 
principal investigator to necessitate patient withdrawal. 
1. Methods 
a) Pre-rinsing of Dialyzers 
Setting up and preparation of the dialyzers will be performed per the clinic’s normal 
procedure. This involves a pre-rinsing step before the start of dialysis.. The priming 
solution will not be infused to the patient. Dialysate flow rate is to be initiated at the 
beginning of the rinsing procedure. All the dialyzers will be pre-rinsed in the same 
procedure. 
b) Heparinization 
The usual heparin type and dosage normally used for each individual patient, including 
the administration regime (bolus injection and continuous infusion), will be maintained 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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for each patient unless specified otherwise by the investigator/physician during the 
evaluation. The total amount of heparin given per treatment will be documented. 
   c) Blood Flow / Dialysate Flow 
Hemodialysis: Blood and dialysate flow rates should be between QB= 300 - 500 ml/min 
and QD= 2 times QB but should follow existing flow rates for the patient, based on clinic 
procedure. Blood flow and dialysate flow should remain unchanged for all patients for the 
duration of dialysis and throughout the evaluation. The ultrafiltration rate, appropriate for 
each patient and treatment will be maintained and recorded. The blood flow will also be 
determined in the fistula using a Doppler flow device. 
   d) Dialysis Regime and Number of Applied Dialyzers 
Three consecutive treatments will be performed with each dialyzer type. Blood sampling 
for measurements will be taken as shown in appendix. 
   e) Performance and Hemocompatibility Parameters to be measured  
Please refer to Appendix. 
 
   f) Blood Sampling 
Blood will be collected pre-, during and post-dialysis at appropriate time intervals (see 
Appendix) for the evaluation of: 
1. Clearance of urea, creatinine, phosphate, beta-2-microglobulin, myoglobin at 
60 min. Five minutes before the collection the flow rate will be adjusted so that 
at time of collection, QB= 350 mL/min, QD= 700 mL/min and UF= 0 for all 
patients. Blood is to be collected from venous side first followed by arterial 
side. 
2. Removal Rate for urea, creatinine, phosphate, beta-2-m and myoglobin at 0 
min and 240 min will be calculated. 
3. Hemocompatibility 
(a) Blood cell count (white blood cell and platelet counts). 
(b) Hb / Hct. 
(c) C5a (activation of complement) 
(d) Thrombin-Antithrombin Complex (TAT) 
 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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The samples will be collected after confirming that the blood and dialysate flows are at 
the targeted rates listed above, venous and arterial pressure at point of collection are to 
be recorded as well. For blood volumes see appendix B. 
   g) Visual estimation of the amount of clotted capillaries 
After dialysis removal of the residual blood is performed by means of ultrafiltration with 
reverse osmosis water from dialysate compartment to blood compartment (0.5-1 bar 
water pressure and the overall appearance of dialyzer will be photographed, with focus 
on the clotted fibers and any residual header blood. This will be carried out at the end of 
each treatment for each dialyzer (3 times each dialyzer). The number of clotted 
capillaries in the dialyzer are counted after removal of the plastic casing and classified by 
the following table. 
  
Number of clotted fibers 
 
0 – 10 
11 – 20 
21 – 50 
51 – 100 
>100 
Score 
1 
2 
3 
4 
5 
 
2. Data Collection 
All data, including blood flow rates, dialysate composition, heparin schedule (i.e. 
concentration in the pre-rinsing solution, bolus and infusion rates, all medications given to 
or taken by the patient, and standard dialysis symptom/events seen routinely in dialysis 
patients will be recorded in the case report form. The patients’ records will contain the 
patients’ names, dates of birth, patients' ESRD diagnosis, and duration of treatment on 
dialysis. Data will be entered into a locked dataset on a locked computer in the Nephrology 
Research Laboratory. Data will be analyzed in house with the exception of digital analysis 
of the photos taken of the dialyzers when dialysis is completed which will be done by the 
sponsor who will be blind to source of the photos. At this time it is not anticipated that any 
individual data, only aggregate results will be sent to the sponsor but if any individual data 
is sent to the sponsor will be blinded. All data will be stored by the Division of Nephrology in 
the Nephrology Research Laboratory for the designated time period and then destroyed. 
 
8. Patient Informed Consent Form 
The investigation has the character of a clinical study according to the US requirements 
and with reference to the European Standard ISO 14155 and the Declaration of Helsinki.  
All patients must be informed about the aim of the study, the risks, and rights and have to 
sign a consent form.  
 
 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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9. Confidentiality 
The principal investigator and evaluation sponsor accept that all details of the evaluation 
be kept confidential at all stages of the evaluation. The sponsor also has the right to 
inspect results prior to any publication or presentation; written consent from the 
evaluation sponsor is required before the results are published or presented at scientific 
meetings. 
 
Date: ____________________  
 
_________________________ 
 
 
 
 
 
 
Principal Investigator 
          
________________________   
 
________________________ 
Clinical Investigator                        Sponsor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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Appendix A: Parameters 
Sampling will be done for every dialysis treatment (3 times per dialyzer, per patient) 
 
Performance 
 
 
60 min 
 
Clearance    Urea   
V, A 
       ‘’     Phosphate 
V, A 
       ‘’     Creatinine 
V, A 
       “      ß2-m 
V, A 
       “      Myoglobin 
V, A 
※Venous sampling will be first, followed by the arterial 
※Do not adopt “slow flow sampling method”. 
 
 
Performance 
 
 
pre 
 
240 min 
 
Removal Rate Urea 
A 
A 
       ‘’     Phosphate 
A 
A 
       ‘’     Creatinine 
A 
A 
       “      ß2-m 
A 
A 
       “      Myoglobin 
A 
A 
 
Sampling will be done once per patient, per dialyzer 
 
Hemocompatibility 
 
 
Pre 
 
15 min 
 
30 min 
 
60 min 
240 min 
WBC 
A 
A 
A 
A 
A 
Platelet Count 
A 
A 
A 
A 
A 
Hb / Hct 
A 
A 
A 
A 
A 
C5a 
A 
A 
A 
A 
A 
TAT 
A 
 
 
A 
A 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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Residual blood behaviour 
 
 
 
 
*) 
A: arterial sample (= pre-dialyzer) 
V: venous sample (= post-dialyzer)            
*) visual evaluation after intensive rinsing 
 
Appendix B: Blood Volumes 
 
Monday Wednwsday Friday Clearence Studies 
84 cc/wk 
    Pre  
  60’ A 
   60’ V 
  Post 
Monday 
7 cc SST 
7 cc SST 
7 cc SST 
7 cc SST 
28 cc/day 
Wednesday 
7 cc SST 
7 cc SST 
7 cc SST 
7 cc SST 
28 cc/day        
Friday  
7 cc SST 
7 cc SST 
7 cc SST 
7 cc SST 
28 cc/day 
 
 
Wednesday Compatibility Studies 
47.5 ml/wk 
 
 
Pre 
 
15’ 
 
30’ 
 
60’ 
 
Post 
CBC 
    2 cc Lavr 
    2 cc Lav 
    2 cc Lav 
    2 cc Lav       2 cc Lav    
10 cc/day 
C5a 
   3 cc Lav 
    3 cc Lav 
   3 cc Lav 
   3 cc Lav 
   3 cc Lav    
15 cc/day 
TAT 
  4.5 cc Lt Blue   4.5 cc Lt Blue   4.5 cc Lt Blue   4.5 cc Lt Blue    4.5 cc Lt Blue       
22.5 cc/day 
Total blood volume = 131.5 ml/week x 3 weeks = 394.5 ml/Patient 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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DCI Corporate Epogen Management Protocol 
1) The goal of the protocol is to maintain Hgb at 11-12 g/dl. Erythropoietin doses are to 
be based upon the estimated dry weight. 
2) The protocol will change the erythropoietin dose no more often than every 4 weeks 
except in the following cases: 
a. Discontinue erythropoietin when Hgb is greater than 13 g/dl. 
b. Increase the erythropoietin dose when Hgb is less than 11 g/dl and the 
previous dose change was a reduction in erythropoietin. 
c. Decrease erythropoietin dose based upon rules 8g-8i when Hgb is between 
12-13 g/dl. 
d. Increase erythropoietin according to rule 8a when Hgb decreased from above 
10 g/dl to below 10 g/dl. 
3) If Hgb is greater than 13 g/dl then discontinue erythropoietin and check Hgb weekly. 
Resume erythropoietin at 25% less than the previous dose as soon as the Hgb is below 
12.5 g/dl. If Hgb remains higher than 12.5 g/dl for more than three months return to 
the clinic’s policy of testing Hgb. 
4) For established patients who have had not had an erythropoietin within the last 3 
months and have a Hgb <11 g/dl start erythropoietin at 300 units/kg/week; for a Hgb 
of 11-11.9 start erythropoietin at 150 units/kg/week. 
5) For new patients without erythropoietin orders who have a Hgb <11 g/dl start 
erythropoietin 300 units/kg/week; for a Hgb of 11-11.9 start erythropoietin at 150 
units/kg/week; for those with a Hgb > 11.9 g/dl do not start erythropoietin. 
6) The weekly doses described in number 4 and 5 above will be equally divided into IV 
dosing for each HD treatment and will be given SQ as a single weekly dose for PD 
patients. 
7) Increase erythropoietin dose by protocol no higher than 900 units/kg/week or 400,000 
units per month. 
8) For patients who have an erythropoietin (EPO) order and the order was not changed 
within the last 4 weeks or cases described in Number 2 above: 
a. If Hgb < 10 g/dl then increase EPO 50% but not less than 300 unites/kg/week. 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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b. If Hgb is between 10-10.9 then increase EPO 25% but not less than 75 
units/kg/week. 
c. If Hgb is between 11-11.9 and Hgb has decreased 0.5 g/dl or more since last 
dose change then increase EPO 10%. 
d. If Hgb is between 11-11.9 and Hgb has increased/decreased 0.5 g/dl since last 
dose change then do not change EOP dose. 
e. If Hgb is between 11-11.7 and Hgb increased0.5 g/dl or more since last dose 
change then do not change EPO dose. 
f. If Hgb is between 11.8-11.9 and Hgb increased 0.5 g/dl since last dose then 
decrease EPO dose by 10%. 
g. If Hgb is between 12-12.4 g/dl and Hgb decreased 0.5 g/dl or more since last 
dose change do not change EPO dose and check Hgb in 2 weeks. 
h. If Hgb is between 12-12.4 and Hgb increased/decreased less than 0.5 g/dl since 
last dose change then decrease EPO 10% and check Hgb in 2 weeks. 
i. If Hgb is between 12-12.4 g/dl and increased 0.5 g/dl or more since last dose 
change then decrease EPO 25% and check Hgb in 2 weeks. 
j. If Hgb is between  12.5-13 g/dl and Hgb decreased 0.5 g/dl or more since last 
dose change then decrease EPO 10% and check Hgb in two weeks. 
k. If Hgb is between 12.5-13 g/dl and Hgb increased/decreased less than 0.5 g/dl 
since last dose change then decrease EPO 25% and check Hgb in 2 weeks. 
l. If Hgb is between 12.5-13 g/dl and Hgb increased 0.5 g/dl or more since last 
dose change decrease EPO 25% and check Hgb weekly. 
m. If Hgb is greater than 13 then stop EPO and check weekly. 
9) All erythropoietin dose decreases will be rounded to the nearest 200 units. All 
erythropoietin dose increases will be rounded up to the nearest 200 units. Dose will 
not be decreased below 400 unites. 
 
 
 
 
 
 
 
 
 

A Clinical Study Comparing The Basic Performance and Blood Compatibility Characteristics of Nipro ELISIO-H, Gambro Polyflux 
Revaclear, and Fresenius Optiflux Artificial Kidneys 
 
Project 2002150 HS 
Version 10 
09/04/2015 
 
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