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Extracorporeal Blood Purification as a Treatment Modality for COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04478539
Recruitment Status : Recruiting
First Posted : July 20, 2020
Last Update Posted : July 20, 2020
Sponsor:
Information provided by (Responsible Party):
Zan Mitrev Clinic

Brief 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.

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


Condition or disease Intervention/treatment Phase
Covid19 Device: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Efficacy and Safety of Extracorporeal Blood Purification to Control Hyperinflammation and Hypercoagulability in COVID-19 Patients
Actual Study Start Date : June 1, 2020
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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

Device: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter

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).





Primary Outcome Measures :
  1. 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


  2. 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.


  3. 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.


  4. 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


  5. 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.



Secondary Outcome Measures :
  1. Changes in Neutrophil-to-Lymphocyte Ratio [ 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.


  2. 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) ]

    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


  3. Changes in the Activation Clotting Time (seconds). [ 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




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Confirmed COVID-19 disease:

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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04478539


Contacts
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Contact: Rodney A Rosalia, PhD +38971305957 rodney.rosalia@zmc.mk
Contact: Dijana Popevski, MD dijana.popevski@zmc.mk

Locations
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North Macedonia
Zan Mitrev Clinic Recruiting
Skopje, North Macedonia, 1000
Contact: Dijana Popevski, MD       dijana.popevski@zmc.mk   
Contact: Dashurie Neziri, MD       dashurie.neziri@zmc.mk   
Sponsors and Collaborators
Zan Mitrev Clinic
Investigators
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Study Director: Zan K Mitrev, MD Zan Mitrev Clinic
Principal Investigator: Petar A Ugurov, MD Zan Mitrev Clinic
Additional Information:
Publications:
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Responsible Party: Zan Mitrev Clinic
ClinicalTrials.gov Identifier: NCT04478539    
Other Study ID Numbers: EBPZ.357
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Zan Mitrev Clinic:
SARS-CoV-2
cytokine storm
Interleukin 6
hypercoagulability
Fibrinogen
D-dimer
Additional relevant MeSH terms:
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Thrombophilia
Hematologic Diseases