Plasma Exchange in Covid-19 Patients With Anti-interferon Autoantibodies

NCT05182515 | Unknown Phase 3 DMC

• 1 other identifier: D20-P060
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 associated mortality remains high despite the advances in therapeutics such as dexamethasone. The severity of COVID-19 results from direct viral cytotoxicity, and the inflammatory response, which is associated with a hypercoagulable state, contribute to lethal hypoxemic pneumonia. During the SARS-CoV-2 replication phase, infected cells secrete chemokines and die by activating the immune system locally. A local inflammatory loop induces tissue destruction, which activates the immune system's circulating cells, leading to another amplifying loop called the cytokine storm. In these phenomena, the integrity of the interferon pathway plays a significant role. Specific impairment of the interferon pathway has been identified in a subset of patients and is associated with high Covid-19 severity. This subset of patients presents preexisting autoimmune disease mediated by autoantibodies directed against IFN. It represents 10.2% (101/987) of patients admitted in ICU with COVID-19 pneumonia, and the observed mortality in this subgroup is 40%. The investigators hypothesized that plasma exchanges (PE) would eliminate these autoantibodies while acting on other mechanisms of the pathogenesis of severe COVID-19, such as cytokine storm or hypercoagulability(7). The EPIC trial aims to demonstrate the efficacy of plasma exchange in the subpopulation of patients with anti-interferon autoantibodies and severe COVID-19 hospitalized in intensive care and on oxygen therapy, high flow or not, receiving non-ventilation or invasive ventilation, on D28 survival.

Conditions

COVID-19

Keywords

type 1 anti-interferon autoantibodies; Cytokine release syndrome; Plasma exchange; Pneumonia; SARS-CoV-2; Severe acute respiratory distress syndrome.

Outcome Measures

Primary Outcomes (1)

• Survival at day 28

  Survival up to day 28

  28 days

Secondary Outcomes (12)

• Survival at day 90

  90 days

• WHO Covid-19 ordinal scale at day 28

  28 days

• WHO Covid-19 ordinal scale at day 90

  90 days

• Lung Injury score (LIS) at day 14

  14 days

• Lung Injury score at day 28

  28 days

Study Arms (2)

Standard of Care

NO INTERVENTION

Standard of care including Dexamethasone

Therapeutic plasma exchanges

EXPERIMENTAL

Drug: Therapeutic plasma exchanges at day 1, 3 and 5 plus Standard of care including Dexamethasone

Drug: Therapeutic plasma exchange

Interventions

Therapeutic plasma exchange DRUG

Plasma exchange techniques reported in COVID-19 vary from study to study. No consensus exists on the use of a specific technique. The use of a central venous catheter will be left to the discretion of investigators. If so, central venous catheter will be inserted through the internal jugular or femoral route under ultrasound control by a trained operator. After radiographic control of the position of the catheter and the absence of complications in the placement of the catheter, plasma exchanges will be carried out. Three plasma exchanges of 1.5 plasma volume will be carried out every 48 hours on D1, D3 and D5. Plasma volume will be assessed by this equation VP = (1-Hct)x70xweight Body(measured). The substitution volume will be 5% albumin as first intervention. The use of a hemofiltration or centrifugation technique will be left to the discretion of each center.

Also known as: Therapeutic plasma exchanges

Therapeutic plasma exchanges

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SARS-CoV-2 infection proven by PCR.
• Positive detection of anti-interferon antibodies.
• Patient, family or deferred consent (emergency clause).

You may not qualify if:

• Pregnant women, parturients and nursing mothers
• Minor patient
• Participation in another interventional trial in progress, with the objective, even secondary, of reducing mortality
• Indication to EPT for another associated pathology
• Contra-indication to EPT, known allergy to albumin 5%.
• Persons under court protection,
• Disturbance of the haemostasis balance (PT\<50%, APTT\>1.5 and fibrinogen \<1g/L)
• Patient presenting a hemorrhagic diathesis (intracranial or digestive bleeding or threatening the functional prognosis)
• Any progressive and advanced pathology whose life expectancy is less than one month
• Bacterial or viral infectious disease (HIV) explaining most of the aggravation

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead

Study Sites (1)

GHU Paris Psychiatrie et Neurosciences

Paris, 75014, France

RECRUITING

Related Publications (16)

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MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome; Pneumonia; Respiratory Distress Syndrome

Interventions

Plasma Exchange

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiration Disorders

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Mazeraud Aurélien, MD, PhD

  GHU Paris Psychiatrie et Neurosciences

  PRINCIPAL INVESTIGATOR

• Sharshar Tarek, MD, PhD

  GHU Paris Psychiatrie et Neurosciences

  STUDY CHAIR

Central Study Contacts

Aurélien Mazeraud, MD, PhD

CONTACT

+33145657413; a.mazeraud@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is an open-label, randomized, multicenter, concurrent, parallel-group, standard of care controlled, to evaluate the safety and efficacy of plasma exchange (PE) in patients with anti-interferon autoantibodies, intensive care admitted for severe or critical symptoms of respiratory illness caused by Coronavirus disease 2019 (COVID-19) defined as "Life-threatening" by the WHO scale, using a group-sequential adaptive design. Approximately 50 participants will be randomized 1:1 to the Investigational or Control arm. Participants randomized to the Investigational arm will receive plasma exchanges (PE) for nearly three days in addition to standard of care (SOC), while participants in the Control arm will receive SOC only. The first plasma exchange session occurs within the first 120 hours of ICU admission. Two interim analyses are planned.

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: January 10, 2022
• Study Start: December 22, 2021
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: January 10, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study protocol, SAP and Data are shared upon request to the sponsor
• Access Criteria: request to the sponsor k.sylla@ghu-paris.fr

Locations

FR (1)