Covid19NCT04478539

Extracorporeal Blood Purification as a Treatment Modality for COVID-19

An observational study of Covid19, run by Zan Mitrev Clinic at 1 site in North Macedonia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

Several studies have suggested a potential clinical benefit of controlling hyper inflammation triggered by SARS-CoV-2/COVID-19. Blood purification, the removal of excessive proinflammatory mediators may control disease progression and support clinical recovery. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Covid19
What is being tested?: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter
Type of treatment: Medical device
How many people: 35 participants
Where: 1 siteNorth Macedonia
Study dates: 1 Jun 2020to 1 Jul 2021
Phase: Observational
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

Study population: COVID positive patients admitted to ICU

Who may be able to join

Confirmed COVID-19 disease:
RT-PCR
Atypical Pneumonia; X-Ray and/or Computed Tomography
≥ 1 oXiris® blood purification cycle

Who cannot join

Pregnancy
Heart failure; severe systolic dysfunction, left ventricular ejection fraction < 25% requiring urgent surgery
Aortic Aneurysms, dissection or rupture requiring urgent surgery
Recent Myocardial Infarction; cardiovascular disease patients requiring urgent surgery

Trial locations and contacts

1 site in 1 country.

North Macedonia1 site

Zan Mitrev Clinic
Skopje, 1000

Other trials in North Macedonia

About this study

Official title: Clinical Efficacy and Safety of Extracorporeal Blood Purification to Control Hyperinflammation and Hypercoagulability in COVID-19 Patients

For this purpose, COVID-19 patients might benefit from treatment with AN69ST hemofilter based extracorporeal blood purification.

Read the detailed description

COVID-19 disease progression is associated with dysregulated immunity, commonly referred to as cytokine storm, in particular, aberrant Interleukin (IL) 6 levels that promote numerous pathological downstream effects. Hyperinflammation is a well-established trigger of multiorgan failure, for example, acute kidney injury. Moreover, recent reports point to a link between hyper inflammation and COVID-19 induced coagulopathy as a result of increased production of clotting factors by the liver.

Despite several lines of evidence pointing to a potential clinical benefit of controlling hyperinflammation triggered by COVID-19, management of COVID-19 remains mostly supportive built around continuous respiratory support.

To this end, considering the underlying immunological character of COVID-19 disease and the high risk of SARS-CoV-2 hyperinflammation to trigger ARDS, hypercoagulability and Acute Kidney Injury (AKI) this study aims to monitor selected biochemical, immunological and coagulation parameters in combination with radiological imaging to guide clinical practice and to tailor therapy consisting of 1) early initiation of blood purification using the oXiris® (AN69ST) filter, 2) systemic heparinisation and 3) respiratory support

Conditions: Covid19
Being tested: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter
Keywords: SARS-CoV-2, cytokine storm, Interleukin 6, hypercoagulability, Fibrinogen, D-dimer
Medical subject headings: COVID-19, Cytokine Release Syndrome, Thrombophilia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Extracorporeal blood purification using the oXiris® (AN69ST) hemofilterDevice
Admitted patients will receive at least 1 cycle of extracorporeal blood purification using the oXiris® (AN69ST) hemofilter (Baxter, IL, USA). The number of cycles of blood purification is determined based on multiple biochemical, immunological, coagulation parameters, radiological imaging and overall clinical condition.
The patient is connected to the Prismaflex® oXiris® system via a double lumen catheter placed in the femoral vein or vena subclavia.
Flow rates will be maintained as follow; effluent dose 35 mL/Kg/h, dialysate 14 - 16 mL/Kg/h, blood 150 mL/min, replacement 16 -18 mL/Kg/h; patient fluid removal is tailored to the individual's volume status, ≈ 100 - 250 mL/h.
The oXiris® extracorporeal and organ support modality will be chosen according to the patient's kidney function; continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) or slow continuous ultrafiltration (SCUF).

Study groups in NCT04478539
Study group	Role	What they receive
COVID-19 patients admitted to the ICU		COVID-19 patients will be treated with the Prismaflex® oXiris® system in the ICU. Treatment will be initiated within 4 - 12 hours after admission upon establishing control of the haemostasis, ACT = Activated Coagulation Time of 180 seconds Receives: Device: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter

What is being measured

The primary outcome is the main question the study is designed to answer.

Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-α (pg/mL)
Systemic levels of IL-6, IL-8 and TNF-α are evaluated to assess the effect of blood purification.
Measurement points: at admission, "before and after a blood purification cycle" and before discharge
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in inflammatory markers; C-Reactive Protein (CRP) (mg/L)
Systemic levels of proinflammatory mediators are measured as a marker for disease severity.
Measurement points: at admission, "before and after a blood purification cycle" and before discharge.
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in thrombocyte counts (10^3 counts/microL)
Systemic levels of thrombocytes are measured as a marker for disease severity.
Measurement points: at admission, "before and after a blood purification cycle" and before discharge.
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in the coagulation marker Fibrinogen (g/L)
Coagulation markers will be followed to assess the effect of systemic heparinisation,
Measurement points, at admission, "before and after a blood purification cycle" and before discharge
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
ICU length of stay after admission (days)
Duration of intensive care will be determined in relation to the number of blood purification cycles
Patients will be followed for the duration of ICU stay.
Measured: An expected average of 4 - 14 hospitalisation days or until hospital discharge (whichever comes first)

Secondary outcomes (3)

Changes in Neutrophil-to-Lymphocyte Ratio
Systemic levels of proinflammatory mediators are measured as a marker for disease severity.
Measurement points: at admission, "before and after a blood purification cycle" and before discharge.
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in the coagulation marker D-Dimers (ng/mL)
Coagulation markers will be followed to assess the effect of systemic heparinisation,
Measurement points, at admission, "before and after a blood purification cycle" and before discharge
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in the Activation Clotting Time (seconds).
Coagulation markers will be followed to assess the effect of systemic heparinisation,
Measurement points, at admission, "before and after a blood purification cycle" and before discharge
Measured: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 20201 Jul 2021

First posted20 Jul 2020
Study start1 Jun 2020
Primary completion1 Jul 2021
Study completion1 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Covid19Studies of the same condition, open and under way.
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: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04478539
Sponsor's protocol ID: EBPZ.357
Status last verified: Nov 2022
First submitted: 14 Jul 2020
Last updated: 1 Dec 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No

Publications

Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp. 2018 May 4;6(1):12. doi: 10.1186/s40635-018-0177-2.
PubMed 29728790
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
PubMed 32192578
The Lancet Haematology. COVID-19 coagulopathy: an evolving story. Lancet Haematol. 2020 Jun;7(6):e425. doi: 10.1016/S2352-3026(20)30151-4. No abstract available.
PubMed 32470428
Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4. doi: 10.1016/j.jaci.2020.05.008. Epub 2020 May 18.
PubMed 32425269
Zhang Y, Yu L, Tang L, Zhu M, Jin Y, Wang Z, Li L. A Promising Anti-Cytokine-Storm Targeted Therapy for COVID-19: The Artificial-Liver Blood-Purification System. Engineering (Beijing). 2021 Jan;7(1):11-13. doi: 10.1016/j.eng.2020.03.006. Epub 2020 Mar 20. No abstract available.
PubMed 32292628

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical Efficacy and Safety of Extracorporeal Blood Purification to Control Hyperinflammation and Hypercoagulability in COVID-19 Patients
ClinicalTrials.gov ID: NCT04478539
Acronym / sponsor ID: EBPZ.357
Conditions: Covid19
Keywords: SARS-CoV-2, cytokine storm, Interleukin 6, hypercoagulability, Fibrinogen, D-dimer
Study type: Observational
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: Zan Mitrev ClinicUniversity, hospital or other
Study start: 1 Jun 2020 (actual)
Primary completion: 1 Jul 2021 (actual)
Study completion: 1 Jul 2021 (actual)
First posted: 20 Jul 2020 (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.

For this purpose, COVID-19 patients might benefit from treatment with AN69ST hemofilter based extracorporeal blood purification.

Detailed description

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 1

Arm	Type	Receives
COVID-19 patients admitted to the ICU	–	Device: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilterCOVID-19 patients will be treated with the Prismaflex® oXiris® system in the ICU. Treatment will be initiated within 4 - 12 hours after admission upon establishing control of the haemostasis, ACT = Activated Coagulation Time of 180 seconds

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: COVID positive patients admitted to ICU

Key inclusion criteria (4 listed)

RT-PCR
Atypical Pneumonia; X-Ray and/or Computed Tomography
≥ 1 oXiris® blood purification cycle

Key exclusion criteria (4 listed)

Pregnancy
Heart failure; severe systolic dysfunction, left ventricular ejection fraction < 25% requiring urgent surgery
Aortic Aneurysms, dissection or rupture requiring urgent surgery
Recent Myocardial Infarction; cardiovascular disease patients requiring urgent surgery

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
Extracorporeal blood purification using the oXiris® (AN69ST) hemofilterAdmitted patients will receive at least 1 cycle of extracorporeal blood purification using the oXiris® (AN69ST) hemofilter (Baxter, IL, USA). The number of cycles of blood purification is determined based on multiple biochemical, immunological, coagulation parameters, radiological imaging and overall clinical condition. The patient is connected to the Prismaflex® oXiris® system via a double lumen catheter placed in the femoral vein or vena subclavia. Flow rates will be maintained as follow; effluent dose 35 mL/Kg/h, dialysate 14 - 16 mL/Kg/h, blood 150 mL/min, replacement 16 -18 mL/Kg/h; patient fluid removal is tailored to the individual's volume status, ≈ 100 - 250 mL/h. The oXiris® extracorporeal and organ support modality will be chosen according to the patient's kidney function; continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) or slow continuous ultrafiltration (SCUF).	Device	COVID-19 patients admitted to the ICU

Primary outcome

Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-α (pg/mL)
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Systemic levels of IL-6, IL-8 and TNF-α are evaluated to assess the effect of blood purification. Measurement points: at admission, "before and after a blood purification cycle" and before discharge
Changes in inflammatory markers; C-Reactive Protein (CRP) (mg/L)
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Systemic levels of proinflammatory mediators are measured as a marker for disease severity. Measurement points: at admission, "before and after a blood purification cycle" and before discharge.
Changes in thrombocyte counts (10^3 counts/microL)
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Systemic levels of thrombocytes are measured as a marker for disease severity. Measurement points: at admission, "before and after a blood purification cycle" and before discharge.
Changes in the coagulation marker Fibrinogen (g/L)
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Coagulation markers will be followed to assess the effect of systemic heparinisation, Measurement points, at admission, "before and after a blood purification cycle" and before discharge
ICU length of stay after admission (days)
Time frame: An expected average of 4 - 14 hospitalisation days or until hospital discharge (whichever comes first)
Duration of intensive care will be determined in relation to the number of blood purification cycles Patients will be followed for the duration of ICU stay.

3 secondary outcomes

Changes in Neutrophil-to-Lymphocyte Ratio
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in the coagulation marker D-Dimers (ng/mL)
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Changes in the Activation Clotting Time (seconds).
Time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)

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 1 Dec 2022.
Background: PubMed 29728790Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp. 2018 May 4;6(1):12. doi: 10.1186/s40635-018-0177-2.
Background: PubMed 32192578Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
Background: PubMed 32470428The Lancet Haematology. COVID-19 coagulopathy: an evolving story. Lancet Haematol. 2020 Jun;7(6):e425. doi: 10.1016/S2352-3026(20)30151-4. No abstract available.
Background: PubMed 32425269Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4. doi: 10.1016/j.jaci.2020.05.008. Epub 2020 May 18.
Background: PubMed 32292628Zhang Y, Yu L, Tang L, Zhu M, Jin Y, Wang Z, Li L. A Promising Anti-Cytokine-Storm Targeted Therapy for COVID-19: The Artificial-Liver Blood-Purification System. Engineering (Beijing). 2021 Jan;7(1):11-13. doi: 10.1016/j.eng.2020.03.006. Epub 2020 Mar 20. No abstract available.
FDA Emergency Use Authorization for Oxiris Blood Purification Filter for COVID-19 TreatmentLink provided by the sponsor.
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.

Zan K Mitrev, MD study director

Zan Mitrev Clinic

Rodney A Rosalia, PhD principal investigator

Zan Mitrev Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Covid19, run by Zan Mitrev Clinic at 1 site in North Macedonia.

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 4 inclusion and 4 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 1 Dec 2022. 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 North Macedonia. 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.

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?

Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-α (pg/mL) (time frame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04478539, which also lists 5 linked publications.

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 1 Dec 2022.