Efficacy of Convalescent Plasma to Treat COVID-19 Patients, a Nested Trial in the CORIMUNO-19 Cohort (CORIPLASM)

• ClinicalTrials.gov Identifier: NCT04345991
• Recruitment Status: Completed
• First Posted: April 15, 2020
• Last Update Posted: October 18, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Etablissement Français du Sang
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: April 10, 2020
• First Posted Date: April 15, 2020
• Last Update Posted Date: October 18, 2021
• Actual Study Start Date: April 15, 2020
• Actual Primary Completion Date: May 28, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 15, 2021)

• Survival without needs of ventilator utilization or use of immunomodulatory drugs (other than steroids) [ Time Frame: At day 14 after randomization ]
  Survival without needs of ventilator utilization (including non- invasive ventilation, NIV) or use of immunomodulatory drugs at day 14 of randomization (WHO score < 6) or additional immunomodulatory treatment (other than steroids). Thus, events considered are the need of ventilator use (including non invasive ventilation, NIV, or use of immunomodulatory drugs), or death.
• WHO progression scale ≥6 [ Time Frame: at day 4 of randomization ]
  WHO progression scale ≥6 at day 4 of randomization

Original Primary Outcome Measures (submitted: April 14, 2020)

• Survival without needs of ventilator utilization or use of immunomodulatory drugs [ Time Frame: At day 14 after randomization ]
  Survival without needs of ventilator utilization (including non- invasive ventilation, NIV) or use of immunomodulatory drugs at day 14 of randomization (WHO score < 6). Thus, events considered are the need of ventilator use (including non invasive ventilation, NIV, or use of immunomodulatory drugs), or death.
• WHO progression scale ≥6 [ Time Frame: at day 4 of randomization ]
  WHO progression scale ≥6 at day 4 of randomization

Current Secondary Outcome Measures (submitted: April 14, 2020)

• Severe adverse events [ Time Frame: up to 28 days ]
  Occurrence of severe adverse events known to be associated with plasma transfusion such as transfusion associated circulatory overload (TACO), transfusion related acute lung injury (TRALI), and severe allergy will be reported. Occurrence of systemic and/or local (lungs) inflammation associated with convalescent plasma transfusion will also be reported.
• WHO progression scale [ Time Frame: at 4, 7 and 14 days after randomization ]
  WHO progression scale at 4, 7 and 14 days after randomization (from stage 4-5 to stage 6 to 10) Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
• Overall survival [ Time Frame: at 14 and 28 days after randomization ]
• Time from randomization to discharge [ Time Frame: Time until discharge up to 28 days ]
• Time to oxygen supply independency [ Time Frame: Time until oxygen supply independency up to 28 days ]
• Survival without needs of ventilator utilization [ Time Frame: At day 14 after randomization ]
  Survival without needs of ventilator utilization (including non- invasive ventilation, NIV) at day 14 of randomization (WHO score < 6). Thus, events considered are the need of ventilator use (including non invasive ventilation, NIV), or death.
• Survival without use of immunomodulatory drugs [ Time Frame: At day 14 after randomization ]
  Survival without use of immunomodulatory drugs at day 14 of randomization (WHO score < 6). Thus, events considered are use of immunomodulatory drugs, or death.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Convalescent Plasma to Treat COVID-19 Patients, a Nested Trial in the CORIMUNO-19 Cohort
• Official Title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - CORIMUNO-CORIPLASM : EFFICACY OF CONVALESCENT PLASMA TO TREAT SARS-COV2 INFECTED PATIENTS

Brief Summary

The coronavirus disease 2019 (COVID-19) viral pneumonia is now a worldwide pandemic caused by the Severe acute respiratory virus coronavirus 2 (SARS-CoV-2). The number of cases, and associated mortality has increased dramatically since the first cases in Wuhan, China in December 2019 . To date, no specific treatment has been proven to be effective for COVID-19. Treatment is currently mainly supportive, with in particular mechanical ventilation for the critically ill patients (6.1% in a series of 1099 cases in China). Novel therapeutic approaches are in acute need. In this context, the therapeutic potential associated with convalescent plasma needs to be explored.

The objective of COVIPLASM trial (a nested trial in the CORIMUNO-19 COHORT) is to study the efficacy of convalescent plasma to treat SARS-COV2 infected patients.

Detailed Description

Hypothesize: early administration of convalescent plasma containing polyclonal neutralizing Abs may inhibit viral entry and replication (as recently suggested in vitro) and consequently blunt an early pro-inflammatory pathogenic endogenous Ab response.

Potential donors of convalescent plasma will be identified through various means, including hospitals taking care of such patient, practitioners treating outpatients or specific social messaging. Convalescent patients at least 14 to 28 days (per at date regulation regarding blood donation) after the symptoms resolution will be invited to undergo plasma apheresis, pending general eligibility such as an age between 18 and 65 years old and weight not less than 50 kg.

Two convalescent plasma units of 200 to 220 ml each will be transfused i.v. as early as possible and no later than 10 days after onset of clinical symptoms. In the absence of acute unforeseen adverse events in the first 3 patients, an additional 2 plasma units of 200/220 ml each will be transfused 24 hours after first 2 units: a total of 4 units / patient. Transfusion monitoring, treatment and reporting of adverse events will be performed per ANSM hemovigilance regulation regarding transfusion of labile blood products as well as through the specific clinical trial vigilance.

An average of 120 participants will be expected (60 participants in each arm). Availability of ABO compatible plasma will be checked by investigator when a Corimmuno patients is eligible. If so, randomization will be undertaken and patient will be offered to participate in this nested trial if he is allocated to the experimental arm.

An interim analysis is performed at mid-trial, but inclusions are not frozen to wait for the interim analysis.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Covid19

Intervention

Drug: Transfusion of COVID-19 convalescent plasma

Two convalescent plasma units of 200 to 220 ml each will be transfused i.v. as early as possible and no later than 10 days after onset of clinical symptoms. In the absence of acute unforeseen adverse events in the first 3 patients, an additional 2 plasma units of 200/220 ml each will be transfused 24 hours after first 2 units: a total of 4 units / patient

Study Arms

• Experimental: COVID-19 convalescent plasma
  A plasma unit provided by a COVID-19 convalescent pathogen-reduced plasma will be used for the treatment of the patients.
  Intervention: Drug: Transfusion of COVID-19 convalescent plasma
• No Intervention: Control patients
  Control patients will receive the best standard of care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 14, 2020): 120
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 28, 2021
• Actual Primary Completion Date: May 28, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients included in the CORIMUNO-19 cohort
• Onset of COVID19 functional signs <8 days (plasma transfusion may occur up to day 10 of onset)
• Mild severity as described in the WHO scale

Exclusion Criteria:

• Pregnancy
• Current documented and uncontrolled bacterial infection.
• Prior severe (grade 3) allergic reactions to plasma transfusion

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04345991
• Other Study ID Numbers: APHP200375-10; 2020-001246-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Etablissement Français du Sang

Investigators

• Principal Investigator: Karine LACOMBE, PU-PH; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: October 2021