Clinical trial NCT05882331: Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19
Official title: Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19 Non-responsive to Remdesivir, Dexamethasone and Pharmacological Immunomodulation: an Investigational Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Keywords: COVID-19
Lead sponsor: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
Sponsor class: OTHER
First posted: 2023-05-31
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Clinical outcomes
timeFrame: All outcomes are assessed at EOT+28 days and compared to data at inclusion.
measure: Virological outcomes
timeFrame: All outcomes are assessed at EOT+28 days and compared to data at inclusion.
measure: Radiological outcomes
timeFrame: All outcomes are assessed at EOT+28 days and compared to data at inclusion.
Secondary outcomes:
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: South Pest Central Hospital, National Institute of Haematology and Infectious Diseases
Study officials:
affiliation: South Pest Central Hospital, National Institute of Hematology and Infectious Diseases
name: Istvan Valyi-Nagy, Prof. Dr.
role: STUDY_DIRECTOR
References: