A multi-centre, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir for the treatment of COVID-19 in Lagos State: study protocol for a randomized controlled trial
A Abayomi, A Osibogun, O Ezechi, K Wright, B Ola, O Ojo, Y Kuyinu, E Zamba, H Abdur-Razzaq, O A Erinoso, S E Anya
Trials, doi:10.1186/s13063-021-05675-x
Background: The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria. Methods: This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software. Discussion: The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria.
Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s13063-021-05675-x. Additional file 1. Research Consent form.
Additional file 2. Case Reporting Forms. Additional file 3. DSMB Charter.
Authors' contributions {31b} All authors contributed to the design of the study and approved the final version. AO, KW, BO, EZ, OAE and SEA conceived the study; AS, OE, KW and YK led on ethics, monitoring and regulatory compliance; OO contributed to the selection of doses of chloroquine and hydroxychloroquine as well as the unblinding protocol; HA, OAE and SEA led on the study design; HA, OAE and SEA prepared the protocol.
Funding {4} The Lagos State Government will provide funding for this trial. The funding body had no role in the design of the study, data collection, analysis and interpretation of data and in writing the manuscript.
Declarations Ethics approval and consent to participate {24} This trial received ethical approval from the Lagos State Health Research Ethics Committee on April 7, 2020, with reference number LREC/06/10/1344. The trial also received regulatory approval from the National Agency for Food and Drug Administration and Control on May 12, 2020, with reference number NAFDAC/DER/SW/CT&D//2020/VOL.1. Participants will be provided with essential information about the trial and invited to sign an informed consent document.
Consent for publication {32} Written informed consent for publication will..
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