Anakinra for COVID-19 Respiratory Symptoms (ANACONDA)

• ClinicalTrials.gov Identifier: NCT04364009
• Recruitment Status: Recruiting
• First Posted: April 27, 2020
• Last Update Posted: May 14, 2020
• Sponsor: University Hospital, Tours
• Collaborators: INSERM CIC-P 1415, University Hospital Center of Tours; Swedish Orphan Biovitrum (SOBI)
• Information provided by (Responsible Party): University Hospital, Tours

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.

Condition or disease	Intervention/treatment	Phase
COVID-19 Infection; ANAKINRA Treatment; Optimized Standard of Care (oSOC)	Drug: Anakinra plus oSOC; Drug: oSOC	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of ANAkinra During Adult " COVID-19 " With Aggravating Respiratory Symptoms: a Multicenter Open-label Controlled Randomized Trial
• Actual Study Start Date: April 27, 2020
• Estimated Primary Completion Date: September 10, 2020
• Estimated Study Completion Date: September 24, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Treatment success [ Time Frame: 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 Outcome Measures :

1. Treatment success [ Time Frame: 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).
2. OMS progression scale (on a 7 point ordinal scale) [ Time Frame: 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.
3. Overall survival [ Time Frame: After 3 days, 10 days, 14 days and 28 days of treatment ]
   Overall survival
4. Time to ICU admission [ Time Frame: Up to 28 days ]
   Time to ICU admission
5. Time to ventilatory support [ Time Frame: Up to 28 days ]
   Time to ventilatory support : extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, non-invasive ventilation, high flow oxygen therapy)
6. Change in National Early Warning Score (NEW)from baseline to Day 3, Day 10, Day 14 and Day 28 [ Time Frame: 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
7. Change in inflammatory parameter [ Time Frame: From baseline to Day 3, Day 10, Day 14 and Day 28 ]
   C-reactive proteine (mg/L)
8. Change in inflammatory parameter [ Time Frame: From baseline to Day 3, Day 10, Day 14 and Day 28 ]
   ferritin (ng/mL)
9. Change in inflammatory parameter [ Time Frame: From baseline to Day 3, Day 10, Day 14 and Day 28 ]
   lymphocyte count (G/L)
10. Change in inflammatory parameter [ Time Frame: From baseline to Day 3, Day 10, Day 14 and Day 28 ]
    fibrinogen (g/l)
11. Hospital length of stay [ Time Frame: Up to 28 days ]
    Hospital length of stay
12. ICU parameter [ Time Frame: Up to 28 days ]
    Need for Vasopressors (yes or no)
13. ICU parameter [ Time Frame: Up to 28 days ]
    Evolution of SpO2/FIO2 ratio (no unit)
14. ICU parameter [ Time Frame: Up to 28 days ]
    Evolution of PaO2/FiO2 ratio (no unit)
15. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 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).
16. Predictors of efficacy of Anakinra [ Time Frame: 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.

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Alexandra AUDEMARD-VERGER, MD-PhD; + 33 247479810; a.audemardverger@chu-tours.fr

Contact: Elodie MOUSSET; +33 247474665; e.mousset@chu-tours.fr

Locations

France

CHRU de TOURS; Recruiting

Tours, France, 37044

Contact: Alexandra AUDEMARD-VERGER

Sponsors and Collaborators

University Hospital, Tours

INSERM CIC-P 1415, University Hospital Center of Tours

Swedish Orphan Biovitrum (SOBI)

Investigators

• Study Director: Alexandra AUDEMARD-VERGER, MD-PhD; University Hospital of Tours

More Information

• Responsible Party: University Hospital, Tours
• ClinicalTrials.gov Identifier: NCT04364009
• Other Study ID Numbers: ANACONDA-COVID-19; 2020-001734-36 ( EudraCT Number ); DR200111 ( Other Identifier: University Hospital of Tours )
• First Posted: April 27, 2020
• Last Update Posted: May 14, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Signs and Symptoms, Respiratory; Signs and Symptoms; Interleukin 1 Receptor Antagonist Protein; Antirheumatic Agents