ApheresisPhase 4NCT05191290
Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation
A Phase 4 study testing unfractionated heparin and Sodium Citrate in people with Apheresis and Anticoagulation, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Apheresis, Anticoagulation
- What is being tested?
- unfractionated heparin and Sodium Citrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSlovenia
- Study dates
- 21 Jan 2022to 30 Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- older than 18 years
- an indication for plasma exchange (plasmapheresis) with albumin solution as a replacement solution
Who cannot join
- contraindication for systemic heparinisation
- acute bleeding
- known active malignancy
- severe infection
- anticoagulant therapy at therapeutic dose
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- Apheresis, Anticoagulation
- Being tested
- unfractionated heparin, Sodium Citrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
unfractionated heparinDrug
standard heparin at 2500 IU i.v. bolus and then 2000 IU/h continuously i.v. for anticoagulation during plasmapheresis
Sodium CitrateDrug
8% sodium citrate at approx. 27 mmol/h i.v. for anticoagulation during plasmapheresis
| Study group | Role | What they receive |
|---|---|---|
| heparin anticoagulation | Active comparator | standard heparin anticoagulation during plasmapheresis Receives: Drug: unfractionated heparin |
| citrate anticoagulation | Experimental | sodium citrate anticoagulation during plasmapheresis Receives: Drug: Sodium Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in serum thrombin-antithrombin complex from baseline to 30 minutes
thrombin-antithrombin complex
Measured: 30 minutes after start of plasmapheresis
change in serum thrombin-antithrombin complex from baseline to the end of plasmapheresis
thrombin-antithrombin complex
Measured: at the end of plasmapheresis procedure
change in serum platelet factor 4 from baseline to 30 minutes
platelet factor 4
Measured: 30 minutes after start of plasmapheresis
change in serum platelet factor 4 from baseline to the end of plasmapheresis
platelet factor 4
Measured: at the end of plasmapheresis procedure
change in serum C5a from baseline to 30 minutes
complement component C5a
Measured: 30 minutes after start of plasmapheresis
change in serum C5a from baseline to the end of plasmapheresis
complement component C5a
Measured: at the end of plasmapheresis procedure
change in serum myeloperoxidase from baseline to 30 minutes
myeloperoxidase
Measured: 30 minutes after start of plasmapheresis
change in serum myeloperoxidase from baseline to the end of plasmapheresis
myeloperoxidase
Measured: at the end of plasmapheresis procedure
Secondary outcomes (5)
complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)
complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)
Measured: during plasmapheresis
comparison of measured platelet factor 4 in patients' serum and filtered plasma
A Bland-Altman agreement analysis
Measured: 30 minutes after start of plasmapheresis
comparison of measured thrombin-antithrombin complex in patients' serum and filtered plasma
A Bland-Altman agreement analysis
Measured: 30 minutes after start of plasmapheresis
comparison of measured C5a in patients' serum and filtered plasma
A Bland-Altman agreement analysis
Measured: 30 minutes after start of plasmapheresis
comparison of measured myeloperoxidase in patients' serum and filtered plasma
A Bland-Altman agreement analysis
Measured: 30 minutes after start of plasmapheresis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start21 Jan 2022
- Primary completion30 Dec 2022
- Study completion30 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ApheresisStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jakob Gubensek, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05191290
- Sponsor's protocol ID
- 0120-310/2017/3
- Status last verified
- Nov 2023
- First submitted
- 12 Dec 2021
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Biocompatibility of Plasmapheresis Procedures With Citrate and Heparin Anticoagulation
- ClinicalTrials.gov ID
- NCT05191290
- Acronym / sponsor ID
- 0120-310/2017/3
- Conditions
- Apheresis, Anticoagulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 21 Jan 2022 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 13 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| heparin anticoagulation | Active comparator | Drug: unfractionated heparinstandard heparin anticoagulation during plasmapheresis |
| citrate anticoagulation | Experimental | Drug: Sodium Citratesodium citrate anticoagulation during plasmapheresis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- older than 18 years
- an indication for plasma exchange (plasmapheresis) with albumin solution as a replacement solution
Key exclusion criteria (5 listed)
- contraindication for systemic heparinisation
- acute bleeding
- known active malignancy
- severe infection
- anticoagulant therapy at therapeutic dose
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| unfractionated heparinstandard heparin at 2500 IU i.v. bolus and then 2000 IU/h continuously i.v. for anticoagulation during plasmapheresis | Drug | heparin anticoagulation |
| Sodium Citrate8% sodium citrate at approx. 27 mmol/h i.v. for anticoagulation during plasmapheresis | Drug | citrate anticoagulation |
Primary outcome
change in serum thrombin-antithrombin complex from baseline to 30 minutes
Time frame: 30 minutes after start of plasmapheresis
thrombin-antithrombin complex
change in serum thrombin-antithrombin complex from baseline to the end of plasmapheresis
Time frame: at the end of plasmapheresis procedure
thrombin-antithrombin complex
change in serum platelet factor 4 from baseline to 30 minutes
Time frame: 30 minutes after start of plasmapheresis
platelet factor 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
change in serum C5a from baseline to 30 minutes
Time frame: 30 minutes after start of plasmapheresis
complement component C5a
change in serum C5a from baseline to the end of plasmapheresis
Time frame: at the end of plasmapheresis procedure
complement component C5a
change in serum myeloperoxidase from baseline to 30 minutes
Time frame: 30 minutes after start of plasmapheresis
myeloperoxidase
change in serum myeloperoxidase from baseline to the end of plasmapheresis
Time frame: at the end of plasmapheresis procedure
myeloperoxidase
5 secondary outcomes
complications during plasmapheresis (hypocalcemia, metabolic alkalosis, clotting)
Time frame: during plasmapheresis
comparison of measured platelet factor 4 in patients' serum and filtered plasma
Time frame: 30 minutes after start of plasmapheresis
comparison of measured thrombin-antithrombin complex in patients' serum and filtered plasma
Time frame: 30 minutes after start of plasmapheresis
comparison of measured C5a in patients' serum and filtered plasma
Time frame: 30 minutes after start of plasmapheresis
comparison of measured myeloperoxidase in patients' serum and filtered plasma
Time frame: 30 minutes after start of plasmapheresis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing unfractionated heparin and Sodium Citrate in people with Apheresis and Anticoagulation, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in serum thrombin-antithrombin complex from baseline to 30 minutes (time frame: 30 minutes after start of plasmapheresis). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.