Clinical trial NCT04364009: Anakinra for COVID-19 Respiratory Symptoms
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
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19 Infection
ANAKINRA Treatment
Optimized Standard of Care (oSOC)
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: INSERM CIC-P 1415, University Hospital Center of Tours
name: Swedish Orphan Biovitrum
First posted: 2020-04-27
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Treatment success
timeFrame: After 14 days of treatment
Secondary outcomes:
measure: Treatment success
timeFrame: After 3 days, 10 days and 28 days of treatment
measure: OMS progression scale (on a 7 point ordinal scale)
timeFrame: After 3 days, 10 days, 14 days and 28 days of treatment
measure: Overall survival
timeFrame: After 3 days, 10 days, 14 days and 28 days of treatment
measure: Time to ICU admission
timeFrame: Up to 28 days
measure: Time to ventilatory support
timeFrame: Up to 28 days
measure: Change in National Early Warning Score (NEW)from baseline to Day 3, Day 10, Day 14 and Day 28
timeFrame: After 3 days, 10 days, 14 days and 28 days of treatment
measure: Change in inflammatory parameter
timeFrame: From baseline to Day 3, Day 10, Day 14 and Day 28
measure: Change in inflammatory parameter
timeFrame: From baseline to Day 3, Day 10, Day 14 and Day 28
measure: Change in inflammatory parameter
timeFrame: From baseline to Day 3, Day 10, Day 14 and Day 28
measure: Change in inflammatory parameter
timeFrame: From baseline to Day 3, Day 10, Day 14 and Day 28
measure: Hospital length of stay
timeFrame: Up to 28 days
measure: ICU parameter
timeFrame: Up to 28 days
measure: ICU parameter
timeFrame: Up to 28 days
measure: ICU parameter
timeFrame: Up to 28 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 28 days
measure: Predictors of efficacy of Anakinra
timeFrame: After 14 days of treatment
Other outcomes:
Locations:
city: Tours
country: France
facility: CHRU de TOURS
Study officials:
affiliation: University Hospital of Tours
name: Alexandra AUDEMARD-VERGER, MD-PhD
role: STUDY_DIRECTOR
References: