COVID-19
Conditions
Keywords
COVID-19
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.
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.
Interventions
PROCEDUREExtracorporeal 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.
Sponsors
Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion 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: 1. severe or critical COVID-19, 2. 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
1. pregnancy or breastfeeding, 2. allergy or contraindications to 8-methoxypsoralen, 3. pre-COVID-19 ECP, 4. written informed consent was not obtainable. Clinical non-response is defined when ≥2 of the following are met, compared to baseline: 1. persistent fever (non-contact tympanal measurement of \>38.0°C) for ≥48 hours, despite antipyretics, 2. persistent or failing COVID-19 severity, according to World Health Organization criteria, by ≥1 stratum after ≥48 hours, 3. persistent or failing partial arterial oxygen tension (PaO2) / inspired oxygen fraction (FiO2), by ≥10% after ≥48 hours, despite respiratory support, 4. radiological progression by infiltrate extension on chest computed tomography (CT), by ≥10% after ≥48 hours, 5. 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: 1. serum lactate dehydrogenase (LDH), 2. serum C-reactive protein (CRP), 3. serum ferritin 4. plasma interleukin-6 (IL-6), 5. D-dimer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Hungary
Outcome results
None listed