COVID-ECP: Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19
Study Details
Study Description
Brief Summary
Optimal approach for adult patients hospitalized with severe and critical COVID-19 non-responsive to antiviral and immunomodulatory drugs is not well established. The study aim is to evaluate feasibility and safety of extracorporeal photopheresis (ECP) in this setting.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
A prospective, single-center investigational study is olanned to be performed at a tertiary referral center for COVID-19. Patients with COVID-19 are screened, and severe or critical COVID-19 cases fulfilling pre-defined clinical and biochemical criteria of non-response for
5 days despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib) are consecutively enrolled. After inclusion, two ECP sessions on two consecutive days per week for 2 weeks are applied. Patients are followed up per protocol from study inclusion, and clinical, virological and radiological outcomes are assessed at end-of-treatment (EOT)+28 days.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Extracorporeal photopheresis arm Patients will receive extracorporeal photopheresis on this arm, in conjucntion to standard COVID-19 treatments (remdesivir, dexamethasone, IL-6- and/or JAK-inhibition). |
Procedure: Extracorporeal photopheresis
ECP is initiated on study inclusion day by Therakos Cellex system, according to manufacturers' instructions. Each patient receives two ECP cycles for 2 weeks, each consisting of two sessions on consecutive days per week (alltogether four sessions), through a peripheral or central venous route. Cycles 1 and 2 are separated by 5 consecutive days. One ECP session takes ~3 hours, and is separated into 4 phases. On priming, the system performes a series of calibrations to ensure proper operation. During collection, 1500 ml of whole blood is processed to collect a concentrated buffy coat containing white blood cells, while other cells and plasma are reinfused. During the photoactive phase, a prescribed dose of 8-methoxypsoralen is added to the buffy coat, which is then circulated through ultraviolet-A photoactivation. During reinfusion phase, treated cells are automatically reinfused to the patient.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Clinical outcomes [All outcomes are assessed at EOT+28 days and compared to data at inclusion.]
Clinical outcomes are all-cause death, invasive mechanical ventilation and ICU admittance requirement.
- Virological outcomes [All outcomes are assessed at EOT+28 days and compared to data at inclusion.]
Virological outcomes are respiratory and blood SARS-CoV-2 RT-PCR positivity.
- Radiological outcomes [All outcomes are assessed at EOT+28 days and compared to data at inclusion.]
Radiological outcomes are radiological progression/regression or fixed infiltration on chest CT scan.
Eligibility Criteria
Criteria
Hospitalized adult (≥18 years at diagnosis) patients with diagnosed COVID-19 of any illness duration are eligible, and screened for inclusion during daily on-site investigator visits. Patients are consecutively enrolled.
Inclusion criteria:
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severe or critical COVID-19,
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clinical and biochemical non-response for >5 consecutive days, despite remdesivir, dexamethasone and immunomodulatory therapies (tocilizumab, baricitinib or ruxolitinib), with or without COVID-19 reconvalescent plasmatherapy, in absence of other causes.
Exclusion criteria:
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pregnancy or breastfeeding,
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allergy or contraindications to 8-methoxypsoralen,
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pre-COVID-19 ECP,
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written informed consent was not obtainable.
Clinical non-response is defined when ≥2 of the following are met, compared to baseline:
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persistent fever (non-contact tympanal measurement of >38.0°C) for ≥48 hours, despite antipyretics,
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persistent or failing COVID-19 severity, according to World Health Organization criteria, by ≥1 stratum after ≥48 hours,
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persistent or failing partial arterial oxygen tension (PaO2) / inspired oxygen fraction (FiO2), by ≥10% after ≥48 hours, despite respiratory support,
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radiological progression by infiltrate extension on chest computed tomography (CT), by ≥10% after ≥48 hours,
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novel requirement of invasive mechanical ventilation, as deemed necessary by an intensive care unit (ICU) team.
Biochemical non-response is defined when ≥2 of the following analytes show persistent or increasing levels by ≥20% after ≥48 hours, compared to baseline:
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serum lactate dehydrogenase (LDH),
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serum C-reactive protein (CRP),
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serum ferritin
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plasma interleukin-6 (IL-6),
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D-dimer.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | South Pest Central Hospital, National Institute of Haematology and Infectious Diseases | Budapest | Hungary | 1097 |
Sponsors and Collaborators
- Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
Investigators
- Study Director: Istvan Valyi-Nagy, Prof. Dr., South Pest Central Hospital, National Institute of Hematology and Infectious Diseases
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- COVID-ECP