Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

Anticoagulation Clinical Trial

Official title:

Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05191290
• Other study ID #: 0120-310/2017/3
• Status: Completed
• Phase: Phase 4
• Start date: January 21, 2022
• Est. completion date: December 30, 2022

Study information

• Verified date: November 2023
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 30, 2022
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anticoagulation
• Apheresis

Intervention

Drug:
• unfractionated heparin
standard heparin at 2500 IU i.v. bolus and then 2000 IU/h continuously i.v. for anticoagulation during plasmapheresis
• Sodium Citrate
8% sodium citrate at approx. 27 mmol/h i.v. for anticoagulation during plasmapheresis

Locations

Country	Name	City	State
Slovenia	University Medical Center Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in serum thrombin-antithrombin complex from baseline to 30 minutes	thrombin-antithrombin complex	30 minutes after start of plasmapheresis
Primary	change in serum thrombin-antithrombin complex from baseline to the end of plasmapheresis	thrombin-antithrombin complex	at the end of plasmapheresis procedure
Primary	change in serum platelet factor 4 from baseline to 30 minutes	platelet factor 4	30 minutes after start of plasmapheresis
Primary	change in serum platelet factor 4 from baseline to the end of plasmapheresis	platelet factor 4	at the end of plasmapheresis procedure
Primary	change in serum C5a from baseline to 30 minutes	complement component C5a	30 minutes after start of plasmapheresis
Primary	change in serum C5a from baseline to the end of plasmapheresis	complement component C5a	at the end of plasmapheresis procedure
Primary	change in serum myeloperoxidase from baseline to 30 minutes	myeloperoxidase	30 minutes after start of plasmapheresis
Primary	change in serum myeloperoxidase from baseline to the end of plasmapheresis	myeloperoxidase	at the end of plasmapheresis procedure
Secondary	complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)	complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)	during plasmapheresis
Secondary	comparison of measured platelet factor 4 in patients' serum and filtered plasma	A Bland-Altman agreement analysis	30 minutes after start of plasmapheresis
Secondary	comparison of measured thrombin-antithrombin complex in patients' serum and filtered plasma	A Bland-Altman agreement analysis	30 minutes after start of plasmapheresis
Secondary	comparison of measured C5a in patients' serum and filtered plasma	A Bland-Altman agreement analysis	30 minutes after start of plasmapheresis
Secondary	comparison of measured myeloperoxidase in patients' serum and filtered plasma	A Bland-Altman agreement analysis	30 minutes after start of plasmapheresis