Extracorporeal Blood Purification as a Treatment Modality for COVID-19

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04478539
• Other study ID #: EBPZ.357
• Status: Completed
• Start date: June 1, 2020
• Est. completion date: July 1, 2021

Study information

• Verified date: November 2022
• Source: Zan Mitrev Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

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).

Locations

Country	Name	City	State
North Macedonia	Zan Mitrev Clinic	Skopje

Sponsors (1)

Lead Sponsor	Collaborator
Zan Mitrev Clinic

Country where clinical trial is conducted

North Macedonia, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-a (pg/mL)	Systemic levels of IL-6, IL-8 and TNF-a are evaluated to assess the effect of blood purification.; Measurement points: at admission, "before and after a blood purification cycle" and before discharge	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Primary	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.	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Primary	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.	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Primary	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	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Primary	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.	An expected average of 4 - 14 hospitalisation days or until hospital discharge (whichever comes first)
Secondary	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.	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Secondary	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	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Secondary	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	Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)

External Links

•   FDA Emergency Use Authorization for Oxiris Blood Purification Filter for COVID-19 Treatment