Determination In-vivo KUF for Diacap Pro Hemodialyser

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is the determination of the in-vivo ultrafiltration coefficient (in-vivo KUF) for Diacap Pro dialyzers following routine dialysis prescription in the United States.

Detailed Description
-----------------
The in-vivo KUF for Diacap Pro High Flux dialysers with the surface sizes of 1.3/ 1.6/ 1.9 sqm will be determined as required by the US guideline Guidance for the Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers 1998 for comparison with the in-vitro KUF data. Clinical data of at least 12 patients will be collected for determination of the in-vivo KUF complemented by safety-, performance-data for the removal of small and middle molecular substances and hemocompatibility data.

Official Title
-----------------
Determination of the In-vivo Ultrafiltration Coefficient and Evaluation of Performance, Hemo- and Biocompatibility- and Safety-data of High Flux Hemodialyser Diacap Pro in Patients With End Stage Renal Disease on Chronic Hemodialysis

Conditions
-----------------
Kidney Failure,Chronic, Renal Insufficiency,Chronic, Kidney Disease, End-Stage, Kidney Insufficiency

Intervention / Treatment
-----------------
* Device: Diacap Pro High-Flux


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent obtained from patient or parents/ guardian. Subject age > 18 Effective blood flow 350 ml/min and dialysate flow in the range of 500 - 800 ml/min On hemodialysis for a minimum of 3 months Use of Cimino- or Gore-tex shunts Routine dialysis-treatment for 240 min and 3 times per week Documented dialysis adequacy parameter spKt/V >=1.2 that has been stable for past 3 months Plan to dialyze at participating hemodialysis center for at least 3-months duration. Free from any currently known unusual clotting or access problems Hepatitis B surface antigen (HbsAg) negative, documented within the past 90 days or Hepatitis B surface antibody (anti-HBs) positive. Anti HCV negative, documented within the past 90 days Anti HIV negative, documented within the past 90 days Hematocrit (HCT) between 25 and 40% or haemoglobin (Hb) not less than 8 g/dL Exclusion Criteria: Patients who are unable to tolerate an effective blood flow of 350 ml/min Patients using catheter for dialysis Pregnant or nursing woman. Women of childbearing potential must agree to avoid pregnancy during the study period Previous plan for extended absences from the participating hemodialysis centre Expected to be transplanted (living related donor) within the maximum of 3 months for the study period Any serious medical conditions or disability, which in the opinion of the investigator, would interfere with treatment or assessment or preclude completion of the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diacap Pro High-Flux<br>1.3/ 1.6/ 1.9 sqm | Device: Diacap Pro High-Flux<br>* During dialysis treatment ultrafiltration rate will be changed following a fixed schedule and resulting changes in Transmembrane Pressure (TMP) recorded to generate data for calculation of the in-vivo KUF.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Transmembrane Pressure (TMP) dependent on differerent ultrafiltration rates for calculation of the in-vivo ultrafiltration coefficient (in-vivo KUF) | UF-rates will be changed over a range starting from 600 ml/min to 1000 ml/min to 1400 ml/min to finally 1800 ml/min and resulting changes in Transmembrane Pressure (TMP) will be documented. | For two of three dialysis sessions each week for a total study period of six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance data dialyzer [ml/min] | For ß2M; Myoglobin; Retinol-Binding-Protein; alpha-1-Microglobulin; Albumin clearance data will be assessed by using serum samples pre- and post dialyzer at timepoints t=0 and t=240 min. | For one of six dialysis sessions each two weeks for a total study period of six weeks | 
| Reduction rates dialyzer [%] | For urea; creatinine; phosphate; ß2-Microglobulin; Myoglobin; Retinol-Binding-Protein; alpha-1 Microglobulin and Albumin reduction rates will be calculated by using serum-levels at timepoints t=0 and t=240 min. | For two of three dialysis sessions each week for a total study period of six weeks | 
| Total removal of proteins [mg/session] | Spent dialysate will be collected during the entire dialysis treatment. Considering dialysate flow rate and ultrafiltration volume concentration of ß2-Microglobulin; Myoglobin; Retinol-Binding-Protein;alpha-1 Microglobulin; Albumin; Total Protein will be used to calculate total removal by multiplying with the effective spent dialysate volume | For one of six dialysis sessions each two weeks for a total study period of six weeks | 
| Complement-activation C3a and C5a [ng/ml] | For complement activation C3a [ng/ml]; C5a [ng/ml] will be assessed at timepoints t=0, t=15; t=60; t=240 min. | For one of six dialysis sessions each two weeks for a total study period of six weeks | 
| Complement-activation TAT III [µg/l] | For complement activation TAT III [µg/l] will be assessed at timepoints t=0, t=15; t=60; t=240 min. | For one of six dialysis sessions each two weeks for a total study period of six weeks | 
| Inflammatory response Interleukin-1, Interleukin-6 and TNF-alpha [pg/ml] | For inflammatory response Interleukin-1 [pg/ml]; Interleukin-6 [pg/ml]; TNF-alpha will be assessed at timepoints t=0; t=15; t=60; t=240 min | For one of six dialysis sessions each two weeks for a total study period of six weeks | 
| Inflammatory response CRP [mg/l] | For inflammatory response CRP[mg/l] will be assessed at timepoints t=0; t=15; t=60; t=240 min | For one of six dialysis sessions each two weeks for a total study period of six weeks | 
| Incidence of Treatment-Emergent Adverse Events | Number of patients presenting adverse events will be assessed following CTCAE v4.0 grading. | November 2016 up to 2 months |