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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

See all articles by Lívia Pimenta Bonifácio

Lívia Pimenta Bonifácio

University of São Paulo (USP) - Ribeirão Preto Medical School

Eduardo Ramacciotti

Science Valley Research Institute

Leandro Barile Agati

Science Valley Research Institute; Science Valley Research Institute

Fernando C. Vilar

University of São Paulo (USP) - Ribeirão Preto Medical School

Anna Christina Tojal da Silva

University of São Paulo (USP) - Ribeirão Preto Medical School

Paulo Louzada-Junior

University of São Paulo (USP) - Ribeirão Preto Medical School

Benedito Antonio Lopes da Fonseca

University of São Paulo (USP) - Ribeirão Preto Medical School

Hayala Cristina Cavenague de Souza

University of São Paulo (USP) - Ribeirão Preto Medical School

Caroline Candida Carvalho de Oliveira

Science Valley Research Institute

Valéria Cristina Resende Aguiar

Science Valley Research Institute

Carlos Augusto de Aguiar Quadros

Hospital e Maternidade Christóvão da Gama

Cesar Dusilek

Hospital do Rocio

Kenji Itinose

Hospital do Rocio

Ricardo Gustavo Zill Risson

Hospital do Rocio

Lucas Roberto Rivabem Ferreira

Hospital do Rocio

Rogério Aparecido Dedivitis

Irmandade Santa Casa de Misericórdia de Porto Alegre

André Sementilli Cortina

Irmandade Santa Casa de Misericórdia de Porto Alegre

Renato Delascio Lopes

Brazilian Clinical Research Institute

Esper Georges Kallas

University of São Paulo (USP) - Hospital das Clinicas HCFMUSP

Fernando Bellissimo-Rodrigues

University of São Paulo (USP) - Ribeirão Preto Medical School

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

Suggested Citation

Pimenta Bonifácio, Lívia and Ramacciotti, Eduardo and Agati, Leandro Barile and Agati, Leandro Barile and Vilar, Fernando C. and Tojal da Silva, Anna Christina and Louzada-Junior, Paulo and Fonseca, Benedito Antonio Lopes da and de Souza, Hayala Cristina Cavenague and de Oliveira, Caroline Candida Carvalho and Aguiar, Valéria Cristina Resende and de Aguiar Quadros, Carlos Augusto and Dusilek, Cesar and Itinose, Kenji and Risson, Ricardo Gustavo Zill and Ferreira, Lucas Roberto Rivabem and Dedivitis, Rogério Aparecido and Cortina, André Sementilli and Lopes, Renato Delascio and Kallas, Esper Georges and Bellissimo-Rodrigues, Fernando, 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). Available at SSRN: https://ssrn.com/abstract=4095747 or http://dx.doi.org/10.2139/ssrn.4095747

Lívia Pimenta Bonifácio (Contact Author)

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Eduardo Ramacciotti

Science Valley Research Institute ( email )

Brazil

Leandro Barile Agati

Science Valley Research Institute

Science Valley Research Institute

Fernando C. Vilar

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Anna Christina Tojal da Silva

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Paulo Louzada-Junior

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Benedito Antonio Lopes da Fonseca

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Rua Luciano Gualberto, 315
São Paulo
Brazil

Hayala Cristina Cavenague De Souza

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Caroline Candida Carvalho De Oliveira

Science Valley Research Institute ( email )

Brazil

Valéria Cristina Resende Aguiar

Science Valley Research Institute ( email )

Brazil

Carlos Augusto De Aguiar Quadros

Hospital e Maternidade Christóvão da Gama ( email )

Brazil

Cesar Dusilek

Hospital do Rocio ( email )

Brazil

Kenji Itinose

Hospital do Rocio ( email )

Ricardo Gustavo Zill Risson

Hospital do Rocio ( email )

Lucas Roberto Rivabem Ferreira

Hospital do Rocio ( email )

Rogério Aparecido Dedivitis

Irmandade Santa Casa de Misericórdia de Porto Alegre ( email )

André Sementilli Cortina

Irmandade Santa Casa de Misericórdia de Porto Alegre ( email )

Renato Delascio Lopes

Brazilian Clinical Research Institute ( email )

Brazil

Esper Georges Kallas

University of São Paulo (USP) - Hospital das Clinicas HCFMUSP ( email )

Brazil

Fernando Bellissimo-Rodrigues

University of São Paulo (USP) - Ribeirão Preto Medical School ( email )

Rua Luciano Gualberto, 315
São Paulo
Brazil

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