Evaluation of Contact Phase Activation During Hemodialysis

Study Overview
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Brief Summary
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Every patient included in the study will undergo 3 standardised hemodialysis treatments, each using a different dialysis membrane (PMMA, PS, AN69ST). The order of the membranes used will be randomized. During each conventional and standardised hemodialysis treatment, 6 blood samples will be taken at different time points (T0, T5, T15, T30, T90, T240) to evaluate coagulation activation (TAT, PF1+2, d-dimers, TF) and, more specifically, activation of the contact phase pathway of coagulation (kallikrein, fXIa, fXIIa).

Official Title
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Evaluation of Contact Phase Activation During Hemodialysis Using Different Dialysis Membranes: a Prospective Randomized Crossover Study

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: PMMA (BKU)
* Device: PS (Phylter)
* Device: AN69ST (Evodial)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated with hemodialysis since at least three months. Hemodialysis treatment schedule of 3 x 4 hours weekly. Arteriovenous fistula (AVF) use for vascular access. Treatment with oral acetylsalicylic acid 80 or 100mg q every day. ≥ 18 years of age. Patients able and agree to provide signed informed consent. Exclusion Criteria: Use of vitamin K antagonists or novel oral anticoagulant therapy. Use of chronic heparin treatment, UFH or LMWH. Use of clopidogrel. Use of ACE-inhibitors. Known allergy against one of the dialysis membranes used during this study (PMMA: BKU®, Toray; PS: Phylter®, Bellco; AN69ST: Evodial®, Gambro). Known heparin-induced trombopenia type 2. Active infection and/or ongoing systemic antimicrobial treatment. Presence of central venous catheter, tunnelled or non-tunnelled and/or AV graft. Hospitalized patients. Planned surgery during study period. Mean Qb of <300ml/min during one of the last 3 dialysis sessions before inclusion. Vascular access dysfunction defined as (a) known AV access outflow tract stenosis, (b) planned vascular access intervention, (c) planned vascular access conversion. Planned conversion of dialysis modality during study period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PMMA (BKU)<br>Patients included in the study will undergo 3 hemodialysis treatments. During the PMMA Arm, patient will be dialyzed using a BKU 1.6 (Toray) dialyzer. All study treatments will be standardized for dialysis access, priming procedure, blood and dialysate flows, anticoagulation therapy and duration of the hemodialysis session. During each study treatment, blood samples will be taken at specified time points (T0, T5, T15, T30, T90, T240) to assess overall coagulation activation (TAT, PF1+2, d-dimers), contact phase activation (kallikrein, fXIa, fXIIa), and activation of the extrinsic coagulation pathway (TF). | Device: PMMA (BKU)<br>* At serial time points before, during and after each study hemodialysis session using a BKU dialyzer, blood samples will be drawn for coagulation activation analyses.<br>|
| Active Comparator: PS (Phylter)<br>Patients included in the study will undergo 3 hemodialysis treatments. During the PS Arm, patient will be dialyzed using a Phylter 1.7 (Bellco) dialyzer. All study treatments will be standardized for dialysis access, priming procedure, blood and dialysate flows, anticoagulation therapy and duration of the hemodialysis session. | Device: PS (Phylter)<br>* At serial time points before, during and after each study hemodialysis session using a Phylter dialyzer, blood samples will be drawn for coagulation activation<br>|
| Active Comparator: AN69ST (Evodial)<br>Patients included in the study will undergo 3 hemodialysis treatments. During the AN69ST Arm, patient will be dialyzed using a Evodial 1.6 (Gambro) dialyzer. All study treatments will be standardized for dialysis access, priming procedure, blood and dialysate flows, anticoagulation therapy and duration of the hemodialysis session. | Device: AN69ST (Evodial)<br>* At serial time points before, during and after each study hemodialysis session using an Evodial dialyzer, blood samples will be drawn for coagulation activation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in contact phase activation induced by hemodialysis treatment, assessed by measurement of plasma kallikrein. | ELISA testing for plasma kallikrein (pg/mL). | Blood samples are taken before hemodialysis treatment start and 5minutes (min), 15min, 30min, 90min and 240min after hemodialysis treatment start. | 
| Change in contact phase activation induced by hemodialysis treatment, assessed by measurement of plasma fXIa. | Chromogenic test for plasma fXIa (mIU/mL). | Blood samples are taken before hemodialysis treatment start and 5min, 15min, 30min, 90min and 240min after hemodialysis treatment start. | 
| Change in contact phase activation induced by hemodialysis treatment, assessed by measurement of plasma fXIIa. | ELISA testing for plasma fXIIa (pg/mL). | Blood samples are taken before hemodialysis treatment start and 5min, 15min, 30min, 90min and 240min after hemodialysis treatment start. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in overall coagulation activation induced by hemodialysis treatment, assessed by measurement of plasma TAT. | ELISA testing for plasma TAT (µg/L). | Blood samples are taken before hemodialysis treatment start and 5min, 15min, 30min, 90min and 240min after hemodialysis treatment start. | 
| Change in overall coagulation activation induced by hemodialysis treatment, assessed by measurement of plasma PF1+2. | ELISA testing for plasma PF1+2 (pmol/L). | Blood samples are taken before hemodialysis treatment start and 5min, 15min, 30min, 90min and 240min after hemodialysis treatment start. | 
| Change in overall coagulation activation induced by hemodialysis treatment, assessed by measurement of plasma d-dimers. | Immunoassay for plasma d-dimers (ng/mL) | Blood samples are taken before hemodialysis treatment start and 5min, 15min, 30min, 90min and 240min after hemodialysis treatment start. | 
| Change in extrinsic coagulation activation during hemodialysis treatment assessed by measurement of plasma Tissue Factor | ELISA testing for plasme Tissue Factor (pg/mL) | Blood samples are taken before hemodialysis treatment start and 5min, 15min, 30min, 90min and 240min after hemodialysis treatment start. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Coagulation activation