Clinical trial NCT04478539: Extracorporeal Blood Purification as a Treatment Modality for COVID-19
Official title: Clinical Efficacy and Safety of Extracorporeal Blood Purification to Control Hyperinflammation and Hypercoagulability in COVID-19 Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Keywords: SARS-CoV-2
cytokine storm
Interleukin 6
hypercoagulability
Fibrinogen
D-dimer
Lead sponsor: Zan Mitrev Clinic
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: COVID positive patients admitted to ICU

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.

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

Eligibility 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

Primary outcomes:
measure: Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-α (pg/mL)
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
measure: Changes in inflammatory markers; C-Reactive Protein (CRP) (mg/L)
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
measure: Changes in thrombocyte counts (10^3 counts/microL)
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
measure: Changes in the coagulation marker Fibrinogen (g/L)
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
measure: ICU length of stay after admission (days)
timeFrame: An expected average of 4 - 14 hospitalisation days or until hospital discharge (whichever comes first)
Secondary outcomes:
measure: Changes in Neutrophil-to-Lymphocyte Ratio
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
measure: Changes in the coagulation marker D-Dimers (ng/mL)
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
measure: Changes in the Activation Clotting Time (seconds).
timeFrame: Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first)
Other outcomes:
Locations:
city: Skopje
country: North Macedonia
facility: Zan Mitrev Clinic
Study officials:
affiliation: Zan Mitrev Clinic
name: Zan K Mitrev, MD
role: STUDY_DIRECTOR
affiliation: Zan Mitrev Clinic
name: Rodney A Rosalia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: 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.
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.