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Efficacy and Safety of Ixekizumab vs. Low-Dose IL-2 vs. Colchicine vs. Standard of Care on the Treatment of Patients Hospitalized with Moderate to Critical Covid-19: A Pilot Randomized Clinical Trial (STRUCK: Survival Trial Using Cyto kine Inhibitors)
17 Pages Posted: 28 Apr 2022
More...Abstract
Background: To evaluate the efficacy and safety of Ixekizumab (IL-17 inhibitor), or low-dose IL-2 or colchicine on top of standard of care (SOC) for Covid-19 treatment.
Methods: A multicenter, open-label, randomized, adaptive study of 4 treatment arms conducted in Brazil. Hospitalized patients with moderate to critical Covid-19 were enrolled according to predetermined eligibility criteria. Patients were randomized to one of 4 arms: standard of care (SOC) alone or combined with Ixekizumab, or low-dose IL-2 or colchicine. The primary efficacy outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a two-point decrease on the WHO seven-category ordinal scale at day 28 after randomization.
Findings: 60 patients were enrolled in the study: 16 in the SOC group, 16 in the Ixekizumab group, 14 in the low-dose IL-2 group, and 14 in the colchicine group. Patients assigned to the colchicine arm presented the greatest improvement in the WHO scale (100%) by day 28, while those in the low dose IL-2 had the worse improvement (64.3%). The colchicine arm presented the lowest mortality rate (0%), while the low dose IL-2 had the highest (21.4%) by day 28 post-enrollment. The frequency of adverse events was lowest in the colchicine group (7.3%). None of the differences observed was statistically significant.
Interpretation: Colchicine added to SOC performed better than Ixekizumab, low-dose IL-2, or SOC alone for hospitalized patients with moderate to critical Covid-19 in this exploratory study. Larger studies are needed to confirm these findings.
Trial registration: NCT04724629https://clinicaltrials.gov/ct2/show/NCT04724629
Funding: Conselho Nacional de Desenvolvimento Científico e Tecnológico ( CNPq) do Brazil, Rede Vírus - Ministério da Ciência e Tecnologia e Inovações (MCTI) do Brazil
Declaration of Interest:
Ethical Approval: After approval of the study by the Institutional Review Board linked to the coordinating center, the University Hospital of the Ribeirão Preto Medical School, University of São Paulo (HCFMRP-USP), the project was forwarded to the Institutional Review Board of five centers selected to conduct the study, with four hospitals located in the state of São Paulo, and one hospital located in the state of Paraná. All selected centers were considered tertiary hospitals, that is, highly complex hospitals that had their own intensive care units, local access to laboratory tests and imaging tests.
Keywords: Covid-19, SARS-CoV-2, Cytokine storm, Ixekizumab, Interleukin-2, Colchicine
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