Effect of Plasmapheresis on Clinical Improvement and Biological Parameters of Patients With Long-haul COVID (PLEXCOVIL)

Effect of Plasmapheresis on Clinical Improvement and Biological Parameters of Patients With Long-haul COVID: PLEXCOVIL Study, a Randomized Controlled Study.

Many patients infected with SARS-Cov-2 present in the months following infection with non-specific symptoms such as non-resolving fatigue, cognitive disorders, dyspnea, headaches, myalgias, sleep disorders, anosmia/ ageusia and post exertion malaise. The persistence of these symptoms is called "post covid syndrome" or "long Covid".

According to the literature, the pathophysiological mechanisms involved in post-covid syndromes would include an inadequate immune response, activation of autoimmunity, persistence of pro-inflammatory biomarkers, endothelial dysfunction and alterations in the intestinal microbiota.

In view of the involved pathophysiological mechanisms, linked to the circulation of pro-inflammatory molecules, autoimmunity or endothelial activation, the role of immuno-modulation in the treatment of long Covid need to be evaluated.

Plasma exchange (PE) by decreasing blood levels of pro-inflammatory cytokines and/or autoimmune markers results in moderate to marked clinical improvement in various types of autoantibody-associated inflammatory, autoimmune and neurological diseases.

The goal of our study is to evaluate the effects of plasmapheresis in patients with moderate to severe long-term COVID compared to patients receiving no treatment.

Study Overview

• Status: Withdrawn
• Conditions: Long-Haul COVID-19
• Intervention / Treatment: Drug: Plasmapheresis; Other: Blood collection; Other: Stool samples; Other: PET scan; Other: Cycle ergometer stress test; Other: Questionnaires at baseline; Other: Medical consultations

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Myriam BENNANI; Phone Number: +33 0413428351; Email: m.bennani@hopital-europeen.fr

Study Locations

• France
  • Marseille, France, 13003
    • Hôpital Européen Marseille
    • Contact: Myriam BENNANI; Phone Number: +33 0413428351; Email: m.bennani@hopital-europeen.fr
    • Principal Investigator: Frédérique RETORNAZ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged ≥ 18 years
• Who have had confirmed SARS-COV2 infection (RT PCR) for at least 6 months
• Having for more than 6 months at least 3 symptoms among the following: fatigue, post effort malaise, dyspnea, headache, diffuse myalgia/arthromyalgia, neuropathic pain, cognitive disorders, anosmia/ageusia
• Whose above symptoms have an impact on daily activities
• And/or on sick leave for more than 3 months
• And/or having to take to bed for more than 2 hours a day
• Having given free and informed written consent
• Being affiliated with or benefiting from social security

Exclusion Criteria:

• With suspected Covid-19 but not confirmed by RT-PCR test
• Having a known history of any other pathology that could be confused with the diagnosis of long COVID: multiple sclerosis, autoimmune disease (lupus and Gougerot syndrome, inflammatory muscle disease, and myasthenia gravis), untreated hypothyroidism, major depression, use of narcotics regular.
• Unable to perform a cycle ergometer stress test
• With innate or drug-induced coagulation disorders (oral or parenteral anticoagulation)
• With contraindications to plasmapheresis such as: lack of peripheral venous access or unstable cardiac pathology
• Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group: receiving plasmapheresis	Drug: Plasmapheresis; 5 sessions of plasma exchanges; Other: Blood collection; Blood collection to assess biological markers at baseline, M3 and M12; Other: Stool samples; Stool samples will be collected from participants at baseline,M3 and M12; Other: PET scan; PET scan at baseline and M6; Other: Cycle ergometer stress test; Cycle ergometer stress test at M6; Other: Questionnaires at baseline; Questionnaires at baseline, M3 and M6
Other: Control group : no treatment	Other: Blood collection; Blood collection to assess biological markers at baseline, M3 and M12; Other: Stool samples; Stool samples will be collected from participants at baseline,M3 and M12; Other: PET scan; PET scan at baseline and M6; Other: Cycle ergometer stress test; Cycle ergometer stress test at M6; Other: Questionnaires at baseline; Questionnaires at baseline, M3 and M6; Other: Medical consultations; Medical consultations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients whose fatigue has decreased by 30% on the Chalder scale at M3 compared to its initial state measured at baseline	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Observation of the evolution of the fatigue (Chalder scale) felt by the patients during the 6 months of the study in the two groups of patients	6 months
Evaluation of the quality of life (SF-36) of patients at month 3 and month 6	3 months and 6 months
Evaluation of the overall impression of change of patients at month 3 and month 6 (PGIC scale)	3 months and 6 months
Evolution at month 3 and month 6 of the following clinical signs: post-exertional malaise, dyspnea, headache, myalgia, neuropathic pain, cognitive impairment, anosmia/ageusia, anxiety/depression	3 months and 6 months
Assessment of patients' functional status at month 3 and month 6 (Post-COVID-19 functional status scale)	3 months 6 months
Evaluation of the professional or student activity at month 3 and month 6	3 months and 6 months
Percentage of patients with 25% improvement in neuromuscular activity of M wave abnormalities at month 6 compared to baseline	6 months
Percentage of patients with improved brain and/or spinal cord metabolism at month 6 compared to baseline	6 months
Evolution of cytokine profiles and lymphocyte activation markers at month 3 and month 6	3 months and 6 months
Rate and evolution of autoimmune markers at month 3 and month 6	3 months and 6 months
Level and evolution of endothelial activity markers at month 3 and month 6	3 months and 6 months
Evaluation of the microbiotic signature at month 3 and month 6	3 months and 6 months

Collaborators and Investigators

• Sponsor: Hôpital Européen Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Chronic Disease; Post-Infectious Disorders; COVID-19; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: 21-

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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