Anakinra for COVID-19 Respiratory Symptoms (ANACONDA)

Efficacy and Safety of ANAkinra During Adult " COVID-19 " With Aggravating Respiratory Symptoms: a Multicenter Open-label Controlled Randomized Trial

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19 Infection; ANAKINRA Treatment; Optimized Standard of Care (oSOC)
• Intervention / Treatment: Drug: oSOC; Drug: Anakinra plus oSOC

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Tours, France, 37044
    • CHRU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Optimized Standard of Care (oSOC); 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.	Drug: oSOC; Optimized Standard of Care (oSOC) on the condition of patients with COVID-19 infection and worsening respiratory symptoms.
Experimental: Anakinra plus Optimized Standard of Care (oSOC); 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	Drug: Anakinra plus oSOC; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	After 14 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment success	Defined as a patient alive and not requiring any of the following: Invasive mechanical ventilation (IMV) or Extracorporeal membrane oxygenation (ECMO).	After 3 days, 10 days and 28 days of treatment
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.	After 3 days, 10 days, 14 days and 28 days of treatment
Overall survival	Overall survival	After 3 days, 10 days, 14 days and 28 days of treatment
Time to ICU admission	Time to ICU admission	Up to 28 days
Time to ventilatory support	Time to ventilatory support : extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, non-invasive ventilation, high flow oxygen therapy)	Up to 28 days
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	After 3 days, 10 days, 14 days and 28 days of treatment
Change in inflammatory parameter	C-reactive proteine (mg/L)	From baseline to Day 3, Day 10, Day 14 and Day 28
Change in inflammatory parameter	ferritin (ng/mL)	From baseline to Day 3, Day 10, Day 14 and Day 28
Change in inflammatory parameter	lymphocyte count (G/L)	From baseline to Day 3, Day 10, Day 14 and Day 28
Change in inflammatory parameter	fibrinogen (g/l)	From baseline to Day 3, Day 10, Day 14 and Day 28
Hospital length of stay	Hospital length of stay	Up to 28 days
ICU parameter	Need for Vasopressors (yes or no)	Up to 28 days
ICU parameter	Evolution of SpO2/FIO2 ratio (no unit)	Up to 28 days
ICU parameter	Evolution of PaO2/FiO2 ratio (no unit)	Up to 28 days
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).	Up to 28 days
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.	After 14 days of treatment

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Collaborators: Swedish Orphan Biovitrum; INSERM CIC-P 1415, University Hospital Center of Tours
• Investigators: Study Director: Alexandra AUDEMARD-VERGER, MD-PhD, University hospital of Tours

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): October 20, 2020
• Study Completion (Actual): November 3, 2020

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Signs and Symptoms, Respiratory; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: ANACONDA-COVID-19; 2020-001734-36 (EudraCT Number); DR200111 (Other Identifier: University Hospital of Tours)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No