Evaluation of Contact Phase Activation During Hemodialysis (c-phact)

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

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).

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Device: PMMA (BKU); Device: PS (Phylter); Device: AN69ST (Evodial)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Jette, Belgium, 1090
    • UZ Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: PMMA (BKU); 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); 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.
ACTIVE_COMPARATOR: PS (Phylter); 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); At serial time points before, during and after each study hemodialysis session using a Phylter dialyzer, blood samples will be drawn for coagulation activation
ACTIVE_COMPARATOR: AN69ST (Evodial); 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); At serial time points before, during and after each study hemodialysis session using an Evodial dialyzer, blood samples will be drawn for coagulation activation

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Karlien François, MD, UZ Brussel, Department of Nephrology

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2017
• Primary Completion (ACTUAL): July 24, 2017
• Study Completion (ACTUAL): July 24, 2017

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (ACTUAL): March 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 15, 2017
• Last Update Submitted That Met QC Criteria: August 11, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Hemodialysis; Coagulation activation
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: UZB-NEF-2016-contactphase

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No