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

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Procedure: Extracorporeal photopheresis

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 Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Balint G Szabo, M.D., Ph.D; Phone Number: +36306445976; Email: szabo.balint.gergely@gmail.com
• Study Contact Backup: Name: Remenyi Peter, M.D.; Phone Number: +3614558100; Email: premenyi@dpckorhaz.hu

Study Locations

• Hungary
  • Budapest, Hungary, 1097
    • Recruiting
    • South Pest Central Hospital, National Institute of Haematology and Infectious Diseases
    • Contact: Balint G SZABO, M.D., Ph.D.; Phone Number: +36306445976; Email: szabo.balint.gergely@gmail.com
    • Contact: Peter REMENYI, M.D.; Phone Number: +3614558100; Email: premenyi@dpckorhaz.hu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Therakos Cellex system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcomes	Clinical outcomes are all-cause death, invasive mechanical ventilation and ICU admittance requirement.	All outcomes are assessed at EOT+28 days and compared to data at inclusion.
Virological outcomes	Virological outcomes are respiratory and blood SARS-CoV-2 RT-PCR positivity.	All outcomes are assessed at EOT+28 days and compared to data at inclusion.
Radiological outcomes	Radiological outcomes are radiological progression/regression or fixed infiltration on chest CT scan.	All outcomes are assessed at EOT+28 days and compared to data at inclusion.

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: May 28, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 28, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVID-ECP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized, individial patient data will be available to other researchers upon reasonbla request from the principal infestigator.
• IPD Sharing Time Frame: Data will be available after publication of the results in peer-reviewed journals.
• IPD Sharing Access Criteria: Anonymized, individial patient data will be available to other researchers upon reasonbla request from the principal infestigator.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No