CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort

Assistance Publique - Hôpitaux de Paris120 enrolled

Overview

The overall objective of the study is to determine the therapeutic effect and tolerance of Eculizumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Eculizumab is a terminal complement inhibitor that has been investigated for more than 10 years in numerous complement-mediated diseases. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Eculizumab administration to patients enrolled in the CORIMUNO-19 cohort. Eculizumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Eculizumab will receive standard of care. Outcomes of Eculizumab-treated patients will be compared with outcomes of standard of care-treated patients as well as with outcomes of patients treated with other immune modulators.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

SARS-CoV-2 COVID19

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients between 18 and 675 years old included in the CORIMUNO-19 cohort 2. Patients belonging to one of the 2 following groups * Group 1: 60 patients not requiring ICU at admission with moderate and severe pneumopathy according to the WHO Criteria of severity of COVID pneumopathy, meeting all of the 2 following criteria: * Respiratory symptoms with radiological findings of pneumonia * Severe pneumonia requiring ≥ 5L/min of oxygen to maintain SpO2 \>97% * Group 2: 60 patients requiring ICU based on Criteria of severity of COVID pneumopathy. * Respiratory failure and requiring mechanical ventilation * Vasopressive support 3. Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating Eculizumab to reduce the risk of meningococcal infection (N meningitidis) \[(Bexsero® (2 injections with a minimum of 1 month interval) + Menveo@ or Niminrex® ) and daily antibiotics (Oracilline®)\]. If vaccination cannot be confirmed or if the patient cannot receive it, the participant should receive prophylactic antibiotics against meningococcal infection prior to initiating Eculizumab treatment and for at least 3 months from the last infusion of Eculizumab. 4. Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified guidance for avoiding pregnancy while on treatment and for 8 months after last dose of Eculizumab. 5- Body weight ≥40 kg 6-Patient and/or alternatively by next-of-kin must be willing and able to give written informed consent according to the applicable regulations including emergency and intensive care contexts Exclusion Criteria: * Patients with exclusion criteria to the CORIMUNO-19 cohort. * Age ≥ 70 years * Pregnancy or lactation * History or unresolved Neisseria meningiditis infection * Ongoing sepsis, presence or suspicion of active and untreated systemic bacterial infection prior study screening and untreated with antibiotics, * Hypersensitivity to any ingredient contained in Eculizumab, including hypersensitivity to murine proteins.

Outcomes

Primary Outcomes

Survival without needs of intubation at day 14

Survival without needs of intubation, events considered are intubation or death

Time frame: 14 days

Change in organ failure at day 3

Change in organ failure at day 3, defined by the relative variation in Sequential Organ Failure Assessment score

Time frame: 3 days

Secondary Outcomes

Intubation free survival at day 14

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

Time frame: Day 14

WHO progression scale at days 4, 7 and 14

WHO progression scale: 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

Time frame: 4, 7 and 14 days

Survival at 14, 28 and 90 days

Overall survival

Time frame: 14, 28 and 90 days

Time to discharge

Time between inclusion and hospital discharge

Time frame: 90 days

Time to oxygen supply independency

Time between inclusion and oxygen supply independency

Time frame: 90 days

Time to negative viral excretion

Time between inclusion and negative viral excretion

Time frame: 90 days

Incidence of secondary infections

Incidence of secondary infections (acquired pneumonia)

Time frame: 90 days

Vasopressor-free survival

Time frame: 90 days

Ventilator-free survival

Time frame: 90 days

28-day ventilator-free days

Number of ventilator-free days alive up to day 28

Time frame: 28 days

Incidence of dialysis

Incidence of dialysis (renal replacement therapy)

Time frame: 90 days

PaO2/FiO2 ratio

Time frame: days 4, 7, 14

Rate of respiratory acidosis at day 4

Number of patients with arterial blood pH of \<7.25, with a partial pressure of arterial carbon dioxide \[Paco2\] of ≥60 mm Hg for \>6 hours

Time frame: 4 days

Time to ICU discharge

Time frame: 90 days

CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts