Anakinra for COVID-19 Respiratory Symptoms

COVID-19 Infection Clinical Trial

— ANACONDA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04364009
• Other study ID #: ANACONDA-COVID-19
• Secondary ID: 2020-001734-36DR
• Status: Terminated
• Phase: Phase 3
• Start date: April 27, 2020
• Est. completion date: November 3, 2020

Study information

• Verified date: April 2020
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 71
• Est. completion date: November 3, 2020
• Est. primary completion date: October 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-TNFa 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.

Related Conditions & MeSH terms

• ANAKINRA Treatment
• COVID-19 Infection
• Optimized Standard of Care (oSOC)
• Signs and Symptoms, Respiratory

Intervention

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
• oSOC
Optimized Standard of Care (oSOC) on the condition of patients with COVID-19 infection and worsening respiratory symptoms.

Locations

Country	Name	City	State
France	CHRU de TOURS	Tours

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Tours	INSERM CIC-P 1415, University Hospital Center of Tours, Swedish Orphan Biovitrum (SOBI)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall survival	Overall survival	After 3 days, 10 days, 14 days and 28 days of treatment
Secondary	Time to ICU admission	Time to ICU admission	Up to 28 days
Secondary	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
Secondary	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
Secondary	Change in inflammatory parameter	C-reactive proteine (mg/L)	From baseline to Day 3, Day 10, Day 14 and Day 28
Secondary	Change in inflammatory parameter	ferritin (ng/mL)	From baseline to Day 3, Day 10, Day 14 and Day 28
Secondary	Change in inflammatory parameter	lymphocyte count (G/L)	From baseline to Day 3, Day 10, Day 14 and Day 28
Secondary	Change in inflammatory parameter	fibrinogen (g/l)	From baseline to Day 3, Day 10, Day 14 and Day 28
Secondary	Hospital length of stay	Hospital length of stay	Up to 28 days
Secondary	ICU parameter	Need for Vasopressors (yes or no)	Up to 28 days
Secondary	ICU parameter	Evolution of SpO2/FIO2 ratio (no unit)	Up to 28 days
Secondary	ICU parameter	Evolution of PaO2/FiO2 ratio (no unit)	Up to 28 days
Secondary	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
Secondary	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