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Completed

NCT Number: NCT05191290

Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

Membrane plasmapheresis is one of the methods for treating immune diseases. Plasmapheresis removes autoantibodies and immune complexes, paraproteins, lipoproteins and reduces the concentration of cytokines. In membrane plasmapheresis, plasma is separated from blood cells by a highly permeable membrane. The filtered plasma is then discarded and replaced with replacement fluid. During the procedure, there is an activation of the coagulation system, because of the extracorporeal blood circulation. The anticoagulation during the procedure is therefore necessary.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University Medical Center Ljubljana

Ljubljana, 1210, Slovenia

About this study

Standard heparin or citrate is routinely used as a method of anticoagulation in plasmapheresis. Citrate provides effective anticoagulation that is completely limited to extracorporeal circulation. Patients who are at increased risk for bleeding, anticoagulation with citrate is a more appropriate method than standard heparin, while in other patients both methods are equivalent.

Citrate anticoagulation is performed by infusing citrate into the arterial line of the extracorporeal system. Citrate binds to plasma calcium and thus inhibits coagulation in the system. Calcium is added to the venous line of the system (when blood returns to the patient) to maintain a normal plasma ionized calcium concentration. Lowering the ionized calcium in the blood in the extracorporeal circulation inhibits the coagulation and activation of other systems (platelets, leukocytes, complement), which affects the biocompatibility of the artificial material and the whole procedure. Biocompatibility is extremely important, since the contact of blood with artificial material activates both the humoral and cellular systems. As part of the humoral immune system, complement is activated by the production of C3, C4 and C5, factor XIIa, there is also an increase in the production of bradykinin, kallikrein, quinine and plasmin, and some proteins are denatured (gamma globulins, fibrinogen, albumins). When the cellular immune system is activated, lymphocytosis can occur and the is also change in function of phagocytes.

All previous studies show that regional anticoagulation with citrate improves biocompatibility in hemodialysis procedures (compared to heparin anticoagulation), but no direct comparison in plasmapheresis has been observed in the literature so far.

Therefore, the investigators want to conduct a prospective randomized study comparing several parameters of heparin and citrate anticoagulation biocompatibility during plasmapheresis. The aim of the study is to demonstrate better biocompatibility in citrate anticoagulation compared to heparin.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • older than 18 years
  • an indication for plasma exchange (plasmapheresis) with albumin solution as a replacement solution

Exclusion criteria

  • contraindication for systemic heparinisation
  • acute bleeding
  • known active malignancy
  • severe infection
  • anticoagulant therapy at therapeutic dose

Treatment and study plan

Unfractionated heparin

Drug

standard heparin at 2500 IU i.v. bolus and then 2000 IU/h continuously i.v. for anticoagulation during plasmapheresis

sodium citrate

Drug

8% sodium citrate at approx. 27 mmol/h i.v. for anticoagulation during plasmapheresis

Primary outcomes

  1. change in serum thrombin-antithrombin complex from baseline to 30 minutes

    Time frame: 30 minutes after start of plasmapheresis

    thrombin-antithrombin complex

  2. change in serum thrombin-antithrombin complex from baseline to the end of plasmapheresis

    Time frame: at the end of plasmapheresis procedure

    thrombin-antithrombin complex

  3. change in serum platelet factor 4 from baseline to 30 minutes

    Time frame: 30 minutes after start of plasmapheresis

    platelet factor 4

  4. change in serum platelet factor 4 from baseline to the end of plasmapheresis

    Time frame: at the end of plasmapheresis procedure

    platelet factor 4

  5. change in serum C5a from baseline to 30 minutes

    Time frame: 30 minutes after start of plasmapheresis

    complement component C5a

  6. change in serum C5a from baseline to the end of plasmapheresis

    Time frame: at the end of plasmapheresis procedure

    complement component C5a

  7. change in serum myeloperoxidase from baseline to 30 minutes

    Time frame: 30 minutes after start of plasmapheresis

    myeloperoxidase

  8. change in serum myeloperoxidase from baseline to the end of plasmapheresis

    Time frame: at the end of plasmapheresis procedure

    myeloperoxidase

Secondary outcomes

  1. complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)

    Time frame: during plasmapheresis

    complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)

  2. comparison of measured platelet factor 4 in patients' serum and filtered plasma

    Time frame: 30 minutes after start of plasmapheresis

    A Bland-Altman agreement analysis

  3. comparison of measured thrombin-antithrombin complex in patients' serum and filtered plasma

    Time frame: 30 minutes after start of plasmapheresis

    A Bland-Altman agreement analysis

  4. comparison of measured C5a in patients' serum and filtered plasma

    Time frame: 30 minutes after start of plasmapheresis

    A Bland-Altman agreement analysis

  5. comparison of measured myeloperoxidase in patients' serum and filtered plasma

    Time frame: 30 minutes after start of plasmapheresis

    A Bland-Altman agreement analysis

Sponsors and collaborators

Lead sponsor

University Medical Centre Ljubljana

Other

Registry information

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Jan 13, 2022
Registry last updated
Nov 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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