ANAKINRA Treatment, COVID-19 Infection, Optimized Standard of Care (oSOC)
Conditions
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.
Interventions
DRUGAnakinra 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
DRUGoSOC
Optimized Standard of Care (oSOC) on the condition of patients with COVID-19 infection and worsening respiratory symptoms.
Sponsors
INSERM CIC-P 1415, University Hospital Center of Tours
Swedish Orphan Biovitrum
University Hospital, Tours
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment success | After 14 days of treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | After 3 days, 10 days, 14 days and 28 days of treatment | Overall survival |
| Time to ICU admission | Up to 28 days | Time to ICU admission |
| Treatment success | After 3 days, 10 days and 28 days of treatment | 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) | After 3 days, 10 days, 14 days and 28 days of treatment | 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 to ventilatory support | Up to 28 days | Time to ventilatory support : extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, non-invasive ventilation, high flow oxygen therapy) |
| ICU parameter | Up to 28 days | Need for Vasopressors (yes or no) |
| Change in inflammatory parameter | From baseline to Day 3, Day 10, Day 14 and Day 28 | C-reactive proteine (mg/L) |
| Hospital length of stay | Up to 28 days | Hospital length of stay |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Up to 28 days | 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 | After 14 days of treatment | 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. |
| Change in National Early Warning Score (NEW)from baseline to Day 3, Day 10, Day 14 and Day 28 | After 3 days, 10 days, 14 days and 28 days of treatment | 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 |
Countries
France
Outcome results
None listed