Variability in Micro-CT Imaging Results to Quantify Dialyzer Clotting

NCT ID: NCT06140563

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-08
• Study Completion Date: 2024-02-15

Brief Summary

Different cross-over studies have been performed investigating dialyzer fiber patency in different dialysis setups. Herewith, post dialysis micro computed tomography (CT) images of the dialyzer were compared. For the best interpretation of such results, one should have an idea about the intrapatient variability. There is also no clue about the impact of long distance transportation and long cold storage on the reproducibility of the micro CT images. Another bottle neck is that, up till now, no biochemical parameter or test has been found associated with the outcome of dialyzer fiber patency post dialysis.

The present study therefore aims at determining the intrapatient variability and the impact on the micro CT results of long distance transportation and long cold storage of the dialyzers. Also, whole blood thrombin generation tests are performed to look for associations with the micro CT results.

Detailed Description

During recent years, different coagulation studies were performed using micro computed tomography (CT) scanning of hemodialyzers post dialysis as a marker for fiber blocking. Each of these studies investigated the impact of either anticoagulation strategy, dialysis strategy, or hemodialyzer type in a cross-over study design in which each patient served as his/her own control.

To date, we still need to answer some remaining questions related to studies using micro CT before we can expand the research and clinical applications to a larger scale:

First, the power of such cross-over studies, with a single session per study arm, depends also partially on the variability over time in the micro CT results within a single patient. While the resolution (25µm) and reproducibility of the micro CT process is established, patients' coagulation status will cause the largest variability in dialyzer outcome among consecutive dialysis sessions, e.g. variation due to infection or vascular access problems. This type of intrapatient variability, quantifying dialyzer outcome with micro CT from comparable but different dialysis sessions, has not yet been studied. Evaluation of the inter- and intra-patient variability of micro CT of dialyzers in chronic hemodialysis patients will inform whether this novel method can be used as an endpoint in future interventional trials of novel anticoagulants.

Second, the micro CT imaging technique, recently paraphrased as the gold standard to quantify clotting, is a very valuable technique in research settings. Clinical practice would profit more from a less burdensome marker of hemodialyzer performance as measured during the dialysis session (not only at the end of a dialysis session). However, none of the available online dialysis machine parameters (i.e., transmembrane pressure, arterial and venous pressure, online clearance monitoring), nor visual scoring of the dialyzer or venous chamber, nor assessment of dialyzer mass post-treatment correlated well with the results of micro CT. Also, the commonly used biochemical parameters only focus on one aspect in the coagulation cascade or/and are not sensitive enough to measure variations in the coagulation system of the patient. As a consequence, they are poorly related to dialyzer outcome as quantified with micro CT. While thrombin generation (TG) is commonly determined in plasma to identify global coagulation phenotype, whole blood TG (WB-TG) tests better mimic physiology by involving also the intrinsic blood cells and platelets, making it a potential biomarker test for coagulation, and this requires investigation.

Third, the previously described studies were all executed at the Ghent University Hospital where dialyzers are prepared for scanning on the spot (i.e., rinsed, dried and stored at 5°C), and with only a short transport time (15min) from the clinic to the micro CT scanner. No hard evidence however exists whether dialyzers, after being prepared for micro CT in a different place, might be transported by flight in e.g. isolated boxes (lasting hours to days). This study will be conducted in collaboration with Regeneron (New York) where a subset of 10 dialyzers will be shipped, imaged using Regeneron's micro CT scanner, and shipped back to Ghent University for repeat imaging.

The main aims of the proposed study are therefore:

1. to determine intrapatient variability of dialyzer fiber blocking as measured by micro CT scanning

2. to investigate whether longer transportation of dialyzers might impact reproducibility of micro CT results by comparing micro CT results between long and short transportation times of dialyzers

3. to determine the anticoagulant effect size of low molecular weight heparin by evaluating the difference in dialyzer fiber patency between full dose and low dose (1/4 dose) low molecular weight heparin treatment, which will inform sample size determination for future interventional studies of other anticoagulants

Conditions

Hemodialysis Complication; Anticoagulants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Normal anticoagulation dosing

Patients are dialyzed during three consecutive hemodialysis sessions with an FX800 Cordiax dialyzer, blood flow of 300mL/min, dialysate flow of 500mL/min and ultrafiltration according to the needs of the patient. At the start of the dialysis session, the normal amount of anticoagulation is administered.

Group Type: EXPERIMENTAL

anticoagulation dosing

Intervention Type: OTHER

In one arm the normal amount of anticoagulation is administered at the dialysis start, while this is only a quarter of the normal amount of anticoagulation in the other arm.

Reduced anticoagulation dosing

Patients are dialyzed during three consecutive hemodialysis sessions with an FX800 Cordiax dialyzer, blood flow of 300mL/min, dialysate flow of 500mL/min and ultrafiltration according to the needs of the patient. At the start of the dialysis session, only one quarter of the normal amount of anticoagulation is administered.

Group Type: EXPERIMENTAL

anticoagulation dosing

Intervention Type: OTHER

In one arm the normal amount of anticoagulation is administered at the dialysis start, while this is only a quarter of the normal amount of anticoagulation in the other arm.

Interventions

anticoagulation dosing

In one arm the normal amount of anticoagulation is administered at the dialysis start, while this is only a quarter of the normal amount of anticoagulation in the other arm.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• stable chronic hemodialysis patient
• well functioning vascular access

Exclusion Criteria

• ultrafiltration rate higher than 4 litre per session
• use of antiplatelets or anticoagulants (apart from acetylsalicylic acid)
• known coagulation disorder
• active inflammation
• malignancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wim Van Biesen, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Ghent University Hospital

Ghent, , Belgium

Countries

Belgium

Other Identifiers

ONZ-2023-0201

Identifier Type: -

Identifier Source: org_study_id