Clinical trial NCT04341584: CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection
Official title: CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection, Nested In The CORIMUNO-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Corona Virus Infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 161
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 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 CORIMUNO-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.


Eligibility criteria: 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 non invasive ventilation or High flow
   * Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR non invasive ventilation 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

Primary outcomes:
measure: Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
timeFrame: Day 1 to Day 14
measure: Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
timeFrame: 4 days
measure: Cumulative Incidence (Percentage) of Participants With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: Day 1 to Day 14
measure: Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5)
timeFrame: 4 days
Secondary outcomes:
measure: WHO Clinical Progression Scale
timeFrame: 4, 7, 14, 28 days
measure: Percentage of Participants Surviving (Overall Survival)
timeFrame: 14, 28 and 90 days
measure: Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)
timeFrame: 28 days
measure: PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: day 1 to day 14
measure: Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency
timeFrame: 28 and 90 days
measure: Cumulative Incidence (Percentage of Participants) of Discharge From Hospital
timeFrame: 28 days
measure: Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: 28 and 90 days
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris
Study officials:
affiliation: Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris
name: Xavier Mariette, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.