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

Abstract

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. Trial registration Pan African Clinical Trials Register PACTR202004801273802. Registered prospectively on April 2, 2020

Perspective Chapter: New Use of the SSRI Fluvoxamine in the Treatment of COVID-19 Symptoms

“…A comprehensive and systematic research about the repurposing of drugs in COVID-19 was conducted by Srivastava and Singh (2021), the results revealed that no drugs passed clinical trials or were approved by the FDA for COVID-19 [23]. In fact, various reports that clinical trials regarding the potential therapeutic possibilities, such as hydroxychloroquine, lopinavir-ritonavir, and ivermectin, showed that choices were unsuccessful in the treatment of COVID-19 patients [24][25][26][27]. Although COVID-19 vaccines were successfully developed and massively distributed, there is a lack of effective treatment [28].…”

Electrochemical Determination of Chloroquine Phosphate in Real Samples Using a Diresorcinate‐1,10‐phenanthrolinecobalt(II)‐Modified Glassy Carbon Electrode

“…[ 2 , 3 , 4 , 5 ] It has been suggested as a potential anticancer drug, [6] and for treatment of COVID‐19. [ 1 , 7 , 8 ] Several studies suggested that interactions of chloroquine with DNA might underlie the antimalarial activity of CQP. [6] …”

“…This is important to reach at decisions whether malaria developed resistance to this medication and alternative solutions. [ 4 , 7 , 8 ]…”

“…[2][3][4][5] It has been suggested as a potential anticancer drug, [6] and for treatment of COVID-19. [1,7,8] Several studies suggested that interactions of chloroquine with DNA might underlie the antimalarial activity of CQP. [6] Side effects of CQP include cardiac arrest, kidney failure, blindness, heart arrhythmias, and cerebral edema, ophthalmic complications and sudden death.…”

“…This is important to reach at decisions whether malaria developed resistance to this medication and alternative solutions. [4,7,8] Different analytical methods including spectrophotometry, [11,12] spectrofluorometry, [5] LC-MS/MS, [2] HPLC-DAD, [3] HPLC, [13] GC-MS, [14] and capillary electrophoresis [15] are reported for the quantification of CQP in biological fluid samples and pharmaceutical forms. However, these methods show some disadvantages such as extended analysis time, complicated sample preparation steps, required trained manpower, high instrumental and analysis cost, which also contributes to the more significant production of chemical residues.…”