Clinical trial NCT04345991: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: COVID 19
Convalescent plasma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Etablissement Français du Sang
First posted: 2020-04-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Survival without needs of ventilator utilization or use of immunomodulatory drugs (other than steroids)
timeFrame: At day 14 after randomization
measure: WHO progression scale ≥6
timeFrame: at day 4 of randomization
Secondary outcomes:
measure: Severe adverse events
timeFrame: up to 28 days
measure: WHO progression scale
timeFrame: at 4, 7 and 14 days after randomization
measure: Overall survival
timeFrame: at 14 and 28 days after randomization
measure: Time from randomization to discharge
timeFrame: Time until discharge up to 28 days
measure: Time to oxygen supply independency
timeFrame: Time until oxygen supply independency up to 28 days
measure: Survival without needs of ventilator utilization
timeFrame: At day 14 after randomization
measure: Survival without use of immunomodulatory drugs
timeFrame: At day 14 after randomization
Other outcomes:
Locations:
city: Paris
country: France
facility: SMIT, Saint Antoine hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Karine LACOMBE, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lacombe K, Hueso T, Porcher R, Mekinian A, Chiarabini T, Georgin-Lavialle S, Ader F, Saison J, Martin-Blondel G, De Castro N, Bonnet F, Cazanave C, Francois A, Morel P, Hermine O, Pourcher V, Michel M, Lescure X, Soussi N, Brun P, Pommeret F, Sellier P, Rousset S, Piroth L, Michot JM, Baron G, de Lamballerie X, Mariette X, Tharaux PL, Resche-Rigon M, Ravaud P, Simon T, Tiberghien P. Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial. BMJ Med. 2023 Oct 27;2(1):e000427. doi: 10.1136/bmjmed-2022-000427. eCollection 2023.