Efficacy of Anakinra in the Management of Patients with COVID-19 Infection: A Randomized Clinical Trial

Background The global pandemic of COVID-19 infections continues to grow worldwide, with rising number of deaths day by day. The hyperinflammation state contributes to the multiorgan failure associated with COVID-19 infections. This study aims to explore the efficacy and safety of anakinra in COVID-19 patients with both respiratory distress and cytokine release syndromes. Methods This was an open-label, multicenter, randomized clinical trial. Patients were randomized in 1:1 ratio to receive standard of care (SOC) alone, or anakinra plus SOC. Adults with confirmed COVID-19 infection with evidence of both respiratory distress and cytokine release syndrome were included. The primary outcome was treatment success at day 14, defined as WHO clinical progression score of ≤3. The primary analysis was based on intention-to-treat population, with p-value of <0.05. Results A total of 80 patients were enrolled in the study. The mean age was 49.9 years (SD=11.7), with 82.5% (n=66) male patients. The primary outcome was not statistically different (87.5% (n=35) in anakinra group vs. 92.5% (n=37) in SOC group, p=0.712). The majority of reported adverse events were mild in severity and not related to the study treatment. Increased aspartate aminotransferase was the only significant adverse event (35% (n=14) in anakinra group vs. 15% (n=6) in SOC group, p=0.039); yet, was not associated with treatment discontinuation. Conclusion In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was not associated with significant improvement in the WHO clinical progression scale. Further studies investigating patients’ subgroups that might benefit from anakinra are warranted. The trial was registered at [ClinicalTrials.gov][1] ([NCT04643678][2]). ### Competing Interest Statement The authors have declared that no competing interests exist. ### Clinical Trial xNCT04643678 ### Funding Statement The study is funded by Medical Research Center at Hamad Medical Corporation, Qatar (MRC-01-20-1095). The study’s funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author has full access to the data and the final responsibility to submit for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was approved by the Institutional Review Board at Hamad Medical Corporation (HMC) Medical Research Center (MRC-01-20-1095) and was registered at [ClinicalTrials.gov][1] ([NCT04643678][2]). The trial was conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. An independent institutional review board and ethics committee approved the trial protocol and any subsequent amendments. The safety of the participants and the evaluation of the benefit–risk balance was overseen by an independent data safety monitoring committee. Written informed consent was obtained from all participants or legally authorized representatives before initiating any trial-related procedures. No additional administrative permissions were required to access the raw data. All data used in this study were fully anonymized before their use. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04643678&atom=%2Fmedrxiv%2Fearly%2F2022%2F07%2F06%2F2022.07.04.22277207.atom