Trial NCT04341584
Publication CORIMUNO-ANA-1 - Mariette X, Lancet Respir Med (2021) (published paper)
Dates: 2020-04-08 to 2020-04-26
Funding: Public/non profit (The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation )
Conflict of interest: No

Methods
RCT
Blinding: Unblinded
Location : Multicenter / France
Follow-up duration (days): 90
Inclusion criteria
  • CORIMUNO-19 cohort:
    SARS-CoV-2 infection (positive on real-time RT-PCR or chest CT scan typical of COVID-19 pneumonia, or both)
    Mild-to-moderate, severe, or critical pneumonia (ie, receiving oxygen at a flow of >3 L/min via mask or nasal cannula and a score of ≥5 points on the WHO Clinical Progression Scale [WHO-CPS] 10-point ordinal scale
  • CORIMUNO-ANA-1:
    C-reactive protein serum concentration of more than 25 mg/L
    Not requiring ICU at admission
    Mild-to-moderate COVID-19 pneumonia with a WHO-CPS score of 5 points, receiving at least 3 L/min of oxygen but without ventilation assistance (eg, high-flow oxygen, non-invasive ventilation, or mechanical ventilation)
Exclusion criteria
  • Known hypersensitivity to anakinra or any of its excipients
  • Pregnancy
  • Current documented bacterial infection
  • An absolute neutrophil count of 1·0 × 109 per L or less
  • A platelet concentration of less than 50 G/L
  • Serum aspartate aminotransferase or serum alanine aminotransferase of more than five- times the upper limit of normal
  • Severe renal insufficiency defined by an estimated glomerular filtration rate of less than 30 mL/min
Interventions
Treatment
Anakinra
200 mg IV twice daily on days 1-3, 100 mg twice daily on day 4, 100 mg once daily on day 5.
If no improvement on morning day 4 (>50% reduction in oxygen requirement), 200 mg twice daily days 4–6, 100mg twice daily day 7, 100 mg once daily day 8
Control
Standard care

Participants
Randomized
participants :
Standard care=57
Anakinra=59
Characteristics of participants
N= 116
Mean age : NR
80 males
Severity : Mild: n=0 / Moderate: n=114 / Severe: n=0 Critical: n=0
Number of vaccinated participants: NR
Primary outcome
In the register
Survival without needs of ventilator utilization at day 14 [ Time Frame: 14 days ];
WHO progression scale ≤ 5 [ Time Frame: 4 days ];
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) or withdrawal of NIV or high flow (for > 48h), at day 14 [ Time Frame: 14 days ];
Decrease of at least one point in WHO progression scale score [ Time Frame: 4 days ]
In the report
The proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 points on the WHO-CPS); and Survival with no need for mechanical or non-invasive ventilation (including high- flow oxygen) at day 14.
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to the published paper, the trial registry, statistical analysis plan and supplementary methods and results were used in data extraction and assessment of risk of bias. The SAP was dated September 21st, 2020 and was version 2.1. This was likely after unblinded data was available for analysis hence it was not used in the risk of bias assessment of domain 5, selection of the reported result. One co-primary outcome in the registry was not reported (decrease of at least one point in WHO progression scale score), but raw data for WHO progression scale scores were reported. This was one of a series of randomized controlled trials testing different therapeutic regimens.
Quote: "On April 23, 2020, the DSMB met and recommended suspension of recruitment for futility on the basis of the interim analysis of the 102 first patients recruited, although the futility boundaries were not formally crossed. The sponsor decided to discontinue the study on April 26, 2020." As a result, the target sample size specified in the registry was not achieved.
Quote: "Another trial within the CORIMUNO platform (CORIMUNO-ANA-2) that aims to assess the effect of anakinra in patients with more severe COVID-19 who are in intensive care units (WHO-CPS score ≥6 points) has now been completed and is being analysed."