Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19

NCT ID: NCT05882331

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2024-08-06

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.

Conditions

COVID-19

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Extracorporeal photopheresis

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Other Intervention Names

Therakos Cellex system

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases

OTHER

Sponsor Role: lead

Responsible Party

Bálint Gergely Szabó

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Istvan Valyi-Nagy, Prof. Dr.

Role: STUDY_DIRECTOR

South Pest Central Hospital, National Institute of Hematology and Infectious Diseases

Locations

South Pest Central Hospital, National Institute of Haematology and Infectious Diseases

Budapest, , Hungary

Countries

Hungary

References

Szabo BG, Remenyi P, Tasnady S, Korozs D, Gopcsa L, Reti M, Varkonyi A, Sinko J, Lakatos B, Szlavik J, Beko G, Bobek I, Valyi-Nagy I. Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study. J Clin Med. 2023 Jul 29;12(15):5000. doi: 10.3390/jcm12155000.

Reference Type: DERIVED

PMID: 37568402 (View on PubMed)

Related Links

https://tmkk.dpckorhaz.hu/

Study website

Other Identifiers

COVID-ECP

Identifier Type: -

Identifier Source: org_study_id