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Anakinra for COVID-19 Respiratory Symptoms (ANACONDA)

Primary Purpose

COVID-19 Infection, ANAKINRA Treatment, Optimized Standard of Care (oSOC)

Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Anakinra plus oSOC
oSOC
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Infection

Eligibility Criteria

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

Inclusion criteria:

  • Male or female≥ 18 years of age
  • Written informed consent of the patient or a proxy
  • Ability for participant to comply with the requirements of the study

  • Hospitalized patient with COVID-19 defined as

    • Positive SARS-CoV2 RT-PCR
    • Or typical COVID-19 Radiographic infiltrates on the CT scan (peripheral ground glass without lung cavitation, lymphadenopathy, or pulmonary nodules) other non COVID-19 diagnosis ruled out.

  • Patient with respiratory symptoms and requirement of oxygen therapy as defined:

    • Oxygen therapy >= 4L/min to maintain Sp02>92% and respiratory rate >=24/min.
    • Or patients under oxygen >= 1L/min and presenting worsening of oxygen requirement defined by an increase of oxygen therapy >= 2L/min to maintain Sp02>92%.
  • Inflammatory component C-Reactive Protein ≥ 50mg/L.
  • Patients within the first 20 days from the onset of the first COVID-19 symptoms
  • Probabilistic antibiotics therapy according to local practice

Non-inclusion criteria:

  • Respiratory failure related to other cause than COVID-19
  • Patients requiring mechanical ventilation at inclusion or requiring oxygen therapy equal or more than 11 liters per min to maintain Sp02>92%
  • Infectious diseases such as severe bacterial infections, aspergillosis, HIV, active HCV, active HBV, active tuberculosis

  • Contra indication to anti-IL1 receptor

    • Known hypersensitivity to Anakinra
    • Absolute neutrophil count (ANC)< 1500/mm3
    • Liver cirrhosis Child-Pugh Score C
    • Live or attenuated vaccine in the past 8 weeks
    • Pregnant or breast-feeding women
  • Patients with either legally protected status or who have been deprived of their freedom
  • Patient included in other interventional therapeutic research (e.g. = concurrent participation in French CoVID-19 is accepted)
  • Patients who have received previous treatment by anti-IL6R, anti-IL-6, anti-IL1R, anti-IL1 or anti-TNFα within 21 days preceding inclusion
  • Absence of Health Insurance
  • Existence of any life-threatening co-morbidity or any other medical condition which,in the opinion of the investigator, makes the patient unsuitable for inclusion.

Sites / Locations

  • CHRU de TOURS

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Optimized Standard of Care (oSOC)

Anakinra plus Optimized Standard of Care (oSOC)

Arm Description

The control group will receive optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry and/or the center COVID-19 therapeutic committees at inclusion and during the follow-up.

The experimental group will receive Anakinra plus optimized Standard of Care. The patients will receive Intravenous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient will receive IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra is 10 Days

Outcomes

Primary Outcome Measures

Treatment success
The primary endpoint is treatment success at Day 14, defined as a patient alive and not requiring any of the following: Invasive mechanical ventilation (IMV) or Extracorporeal membrane oxygenation (ECMO).

Secondary Outcome Measures

Treatment success
Defined as a patient alive and not requiring any of the following: Invasive mechanical ventilation (IMV) or Extracorporeal membrane oxygenation (ECMO).
OMS progression scale (on a 7 point ordinal scale)
1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;6. Hospitalized, on invasive mechanical ventilation or ECMO;7. Death.
Overall survival
Overall survival
Time to ICU admission
Time to ICU admission
Time to ventilatory support
Time to ventilatory support : extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, non-invasive ventilation, high flow oxygen therapy)
Change in National Early Warning Score (NEW)from baseline to Day 3, Day 10, Day 14 and Day 28
The National Early Warning Score (NEWS) determines the degree of illness of a patient using six physiological findings and one observation. Score from 0 to 20, 0 mean a worse outcome, 20 mean a better outcome
Change in inflammatory parameter
C-reactive proteine (mg/L)
Change in inflammatory parameter
ferritin (ng/mL)
Change in inflammatory parameter
lymphocyte count (G/L)
Change in inflammatory parameter
fibrinogen (g/l)
Hospital length of stay
Hospital length of stay
ICU parameter
Need for Vasopressors (yes or no)
ICU parameter
Evolution of SpO2/FIO2 ratio (no unit)
ICU parameter
Evolution of PaO2/FiO2 ratio (no unit)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Occurrence of serious adverse events during the study, including infection (bacterial, parasitic, mycotic and viral infection), septic shock, Ankanira hypersensitivity, hepatic damages (SGOT/SGPT, alkaline phosphatase, gammaGT) and neutropenia (Blood count).
Predictors of efficacy of Anakinra
The correlation between several of clinical parameters at inclusion (including level of oxygen requirement (saturation), respiratory rate (per min), temperature (°C)…), biological parameters :including, CRP (mg/L), ferritin (µg/L), LDH (UI/L), lymphocyte count (G/L), eosinophil count (G/L), Ddimers (ng/mM), platelet count (G/L), polymorphonuclear count (G/L)...with the primary end point will be explored.

Full Information

First Posted
April 17, 2020
Last Updated
January 14, 2021
Sponsor
University Hospital, Tours
Collaborators
INSERM CIC-P 1415, University Hospital Center of Tours, Swedish Orphan Biovitrum
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1. Study Identification

Unique Protocol Identification Number
NCT04364009
Brief Title
Anakinra for COVID-19 Respiratory Symptoms
Acronym
ANACONDA
Official Title
Efficacy and Safety of ANAkinra During Adult " COVID-19 " With Aggravating Respiratory Symptoms: a Multicenter Open-label Controlled Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Efficiency and safety reasons
Study Start Date
April 27, 2020 (Actual)
Primary Completion Date
October 20, 2020 (Actual)
Study Completion Date
November 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
Collaborators
INSERM CIC-P 1415, University Hospital Center of Tours, Swedish Orphan Biovitrum

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 main objective of the ANACONDA-COVID-19 trial is to assess the efficacy of Anakinra + optimized Standard of Care (oSOC) as compared to oSOC alone on the condition of patients with COVID-19 infection and worsening respiratory symptoms. Success defined as patient alive and free of invasive mechanical ventilation (IMV) and free of Extracorporeal Membrane Oxygenation (ECMO) at Day 14.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Infection, ANAKINRA Treatment, Optimized Standard of Care (oSOC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
ANACONDA study is a French multicentre, open-label, randomized, controlled superiority trial comparing the administration of optimized standard of care and Anakinra versus optimized standard of care alone in patients hospitalized in a medical unit with COVID-19.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Optimized Standard of Care (oSOC)
Arm Type
Active Comparator
Arm Description
The control group will receive optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry and/or the center COVID-19 therapeutic committees at inclusion and during the follow-up.
Arm Title
Anakinra plus Optimized Standard of Care (oSOC)
Arm Type
Experimental
Arm Description
The experimental group will receive Anakinra plus optimized Standard of Care. The patients will receive Intravenous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient will receive IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra is 10 Days
Intervention Type
Drug
Intervention Name(s)
Anakinra plus oSOC
Intervention Description
Anakinra plus Optimized Standard of Care (oSOC) on the condition of patients with COVID-19 infection and worsening respiratory symptoms. The patients will receive intraveinous injection of Anakinra 400mg from Day 1 to Day 3 (two injections of 100 mg each 12 hours) and 200mg the remaining 7 days. The total duration of Anakinra is 10 Days. Efficient dosage of Anakinra as previously described will be continued until Day 10
Intervention Type
Drug
Intervention Name(s)
oSOC
Intervention Description
Optimized Standard of Care (oSOC) on the condition of patients with COVID-19 infection and worsening respiratory symptoms.
Primary Outcome Measure Information:
Title
Treatment success
Description
The primary endpoint is treatment success at Day 14, defined as a patient alive and not requiring any of the following: Invasive mechanical ventilation (IMV) or Extracorporeal membrane oxygenation (ECMO).
Time Frame
After 14 days of treatment
Secondary Outcome Measure Information:
Title
Treatment success
Description
Defined as a patient alive and not requiring any of the following: Invasive mechanical ventilation (IMV) or Extracorporeal membrane oxygenation (ECMO).
Time Frame
After 3 days, 10 days and 28 days of treatment
Title
OMS progression scale (on a 7 point ordinal scale)
Description
1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;6. Hospitalized, on invasive mechanical ventilation or ECMO;7. Death.
Time Frame
After 3 days, 10 days, 14 days and 28 days of treatment
Title
Overall survival
Description
Overall survival
Time Frame
After 3 days, 10 days, 14 days and 28 days of treatment
Title
Time to ICU admission
Description
Time to ICU admission
Time Frame
Up to 28 days
Title
Time to ventilatory support
Description
Time to ventilatory support : extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, non-invasive ventilation, high flow oxygen therapy)
Time Frame
Up to 28 days
Title
Change in National Early Warning Score (NEW)from baseline to Day 3, Day 10, Day 14 and Day 28
Description
The National Early Warning Score (NEWS) determines the degree of illness of a patient using six physiological findings and one observation. Score from 0 to 20, 0 mean a worse outcome, 20 mean a better outcome
Time Frame
After 3 days, 10 days, 14 days and 28 days of treatment
Title
Change in inflammatory parameter
Description
C-reactive proteine (mg/L)
Time Frame
From baseline to Day 3, Day 10, Day 14 and Day 28
Title
Change in inflammatory parameter
Description
ferritin (ng/mL)
Time Frame
From baseline to Day 3, Day 10, Day 14 and Day 28
Title
Change in inflammatory parameter
Description
lymphocyte count (G/L)
Time Frame
From baseline to Day 3, Day 10, Day 14 and Day 28
Title
Change in inflammatory parameter
Description
fibrinogen (g/l)
Time Frame
From baseline to Day 3, Day 10, Day 14 and Day 28
Title
Hospital length of stay
Description
Hospital length of stay
Time Frame
Up to 28 days
Title
ICU parameter
Description
Need for Vasopressors (yes or no)
Time Frame
Up to 28 days
Title
ICU parameter
Description
Evolution of SpO2/FIO2 ratio (no unit)
Time Frame
Up to 28 days
Title
ICU parameter
Description
Evolution of PaO2/FiO2 ratio (no unit)
Time Frame
Up to 28 days
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Occurrence of serious adverse events during the study, including infection (bacterial, parasitic, mycotic and viral infection), septic shock, Ankanira hypersensitivity, hepatic damages (SGOT/SGPT, alkaline phosphatase, gammaGT) and neutropenia (Blood count).
Time Frame
Up to 28 days
Title
Predictors of efficacy of Anakinra
Description
The correlation between several of clinical parameters at inclusion (including level of oxygen requirement (saturation), respiratory rate (per min), temperature (°C)…), biological parameters :including, CRP (mg/L), ferritin (µg/L), LDH (UI/L), lymphocyte count (G/L), eosinophil count (G/L), Ddimers (ng/mM), platelet count (G/L), polymorphonuclear count (G/L)...with the primary end point will be explored.
Time Frame
After 14 days of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Male or female≥ 18 years of age Written informed consent of the patient or a proxy Ability for participant to comply with the requirements of the study Hospitalized patient with COVID-19 defined as Positive SARS-CoV2 RT-PCR Or typical COVID-19 Radiographic infiltrates on the CT scan (peripheral ground glass without lung cavitation, lymphadenopathy, or pulmonary nodules) other non COVID-19 diagnosis ruled out. Patient with respiratory symptoms and requirement of oxygen therapy as defined: Oxygen therapy >= 4L/min to maintain Sp02>92% and respiratory rate >=24/min. Or patients under oxygen >= 1L/min and presenting worsening of oxygen requirement defined by an increase of oxygen therapy >= 2L/min to maintain Sp02>92%. Inflammatory component C-Reactive Protein ≥ 50mg/L. Patients within the first 20 days from the onset of the first COVID-19 symptoms Probabilistic antibiotics therapy according to local practice Non-inclusion criteria: Respiratory failure related to other cause than COVID-19 Patients requiring mechanical ventilation at inclusion or requiring oxygen therapy equal or more than 11 liters per min to maintain Sp02>92% Infectious diseases such as severe bacterial infections, aspergillosis, HIV, active HCV, active HBV, active tuberculosis Contra indication to anti-IL1 receptor Known hypersensitivity to Anakinra Absolute neutrophil count (ANC)< 1500/mm3 Liver cirrhosis Child-Pugh Score C Live or attenuated vaccine in the past 8 weeks Pregnant or breast-feeding women Patients with either legally protected status or who have been deprived of their freedom Patient included in other interventional therapeutic research (e.g. = concurrent participation in French CoVID-19 is accepted) Patients who have received previous treatment by anti-IL6R, anti-IL-6, anti-IL1R, anti-IL1 or anti-TNFα within 21 days preceding inclusion Absence of Health Insurance Existence of any life-threatening co-morbidity or any other medical condition which,in the opinion of the investigator, makes the patient unsuitable for inclusion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandra AUDEMARD-VERGER, MD-PhD
Organizational Affiliation
University Hospital of Tours
Official's Role
Study Director
Facility Information:
Facility Name
CHRU de TOURS
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Anakinra for COVID-19 Respiratory Symptoms

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