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CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection (CORIMUNO-ANA)

Primary Purpose

Corona Virus Infection

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Anakinra
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients included in the CORIMUNO-19 cohort
  2. Patients with C-reactive protein level (CRP) > 25 mg / L the day or the day before the infusion)

  3. Patients belonging to one of the 2 following groups:

    • Group 1: patients meeting all of the following criteria: 1) Requiring more than 3L/min of oxygen; 2) WHO progression scale = 5; 3) No NIV or High flow
    • Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR NIV OR High flow), with a WHO progression scale ≥ 6, and no do-not-resuscitate (DNR) order

Exclusion Criteria:

  • Patients with exclusion criteria to the CORIMUNO-19 cohort.
  • Known hypersensitivity to Anakinra or to any of their excipients.
  • Pregnancy
  • Current documented bacterial infection.

  • Patient with any of following laboratory results out of the ranges detailed below at screening:

    • Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
    • Haemoglobin level: no limitation
    • Platelets (PLT) < 50 G /L
    • SGOT or SGPT > 5N
    • Severe renal insufficiency with Glomerular filtration rate < 30 ml / mn

Sites / Locations

  • Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

ANAKINRA

Standard of care

Arm Description

Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter

Outcomes

Primary Outcome Measures

Survival without needs of ventilator utilization at day 14
Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
WHO progression scale ≤ 5
Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5.
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) or withdrawal of NIV or high flow (for > 48h), at day 14
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Decrease of at least one point in WHO progression scale score
Proportion of patients with a decrease of WHO score of at least 1 point at day 4

Secondary Outcome Measures

WHO progression scale
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.
Survival
Overall survival.
28-day ventilator free-days
Respiratory acidosis
arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours.
PaO2/FiO2 ratio
Evolution of PaO2/FiO2 ratio.
Time to oxygen supply independency
Time to oxygen supply independency.
Duration of hospitalization
Duration of hospitalization.
Time to negative viral excretion
Time to negative viral excretion.
Time to ICU discharge
Time to ICU discharge.
Time to hospital discharge
Time to hospital discharge.

Full Information

First Posted
April 7, 2020
Last Updated
January 29, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04341584
Brief Title
CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection
Acronym
CORIMUNO-ANA
Official Title
CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection, Nested In The CORIMUNO-19
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
April 8, 2020 (Actual)
Primary Completion Date
May 10, 2020 (Actual)
Study Completion Date
July 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the COVIMUNO-19 cohort. Anakinra will be administered to consenting adult patients hospitalized with CORVID-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 Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
161 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ANAKINRA
Arm Type
Experimental
Arm Description
Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
Arm Title
Standard of care
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Anakinra
Intervention Description
Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
Primary Outcome Measure Information:
Title
Survival without needs of ventilator utilization at day 14
Description
Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Time Frame
14 days
Title
WHO progression scale ≤ 5
Description
Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5.
Time Frame
4 days
Title
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) or withdrawal of NIV or high flow (for > 48h), at day 14
Description
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Time Frame
14 days
Title
Decrease of at least one point in WHO progression scale score
Description
Proportion of patients with a decrease of WHO score of at least 1 point at day 4
Time Frame
4 days
Secondary Outcome Measure Information:
Title
WHO progression scale
Description
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
7 and 14 days
Title
Survival
Description
Overall survival.
Time Frame
14, 28 and 90 days
Title
28-day ventilator free-days
Time Frame
28 days
Title
Respiratory acidosis
Description
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
Title
PaO2/FiO2 ratio
Description
Evolution of PaO2/FiO2 ratio.
Time Frame
day 1 to day 14
Title
Time to oxygen supply independency
Description
Time to oxygen supply independency.
Time Frame
14 days
Title
Duration of hospitalization
Description
Duration of hospitalization.
Time Frame
90 days
Title
Time to negative viral excretion
Description
Time to negative viral excretion.
Time Frame
90 days
Title
Time to ICU discharge
Description
Time to ICU discharge.
Time Frame
90 days
Title
Time to hospital discharge
Description
Time to hospital discharge.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients included in the CORIMUNO-19 cohort Patients with C-reactive protein level (CRP) > 25 mg / L the day or the day before the infusion) Patients belonging to one of the 2 following groups: Group 1: patients meeting all of the following criteria: 1) Requiring more than 3L/min of oxygen; 2) WHO progression scale = 5; 3) No NIV or High flow Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR NIV OR High flow), with a WHO progression scale ≥ 6, and no do-not-resuscitate (DNR) order Exclusion Criteria: Patients with exclusion criteria to the CORIMUNO-19 cohort. Known hypersensitivity to Anakinra or to any of their excipients. Pregnancy Current documented bacterial infection. Patient with any of following laboratory results out of the ranges detailed below at screening: Absolute neutrophil count (ANC) ≤ 1.0 x 109/L Haemoglobin level: no limitation Platelets (PLT) < 50 G /L SGOT or SGPT > 5N Severe renal insufficiency with Glomerular filtration rate < 30 ml / mn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier Mariette, MD, PhD
Organizational Affiliation
Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris
City
Le Kremlin-Bicêtre
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33493450
Citation
CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir Med. 2021 Mar;9(3):295-304. doi: 10.1016/S2213-2600(20)30556-7. Epub 2021 Jan 22.
Results Reference
derived

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CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection

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