A Randomized Controlled Trial of Ivermectin Monotherapy versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in COVID- 19 Patients in Nigeria
O E Babalola, Y A Ndanusa, A A Ajayi, J O Ogedengbe, Y Thairu, O Omede
Journal of Infectious Diseases and Epidemiology, doi:10.23937/2474-3658/1510233
The efficacy of Ivermectin (IVM) against SARS-CoV-2 has been demonstrated in vitro, while several clinical studies suggest that it is efficacious and safe in reducing morbidity and mortality. Hydroxychloroquine (HCQ, Quinoric®), IVM and Azithromycin(AZM, Zithromax®) (HIA therapy) is being used in several low-and middle-income countries (LMIC) where more expensive medications such as Remdesivir are out of reach. In this study, we set out to compare the efficacy of IVM monotherapy with HIA combination therapy.
Methods: This was a single-blind, randomized control trial, of 2 parallel groups of COVID-19 Positive Nigerians. Thirty (30) patients received Ivermectin (Mectizan®) 200 mcg/ kg daily for five days, while 31 patients received HIA triple therapy. Viral cycle threshold (Ct) at pre-treatment baseline, and days 2, 5, 14 and 21 were measured for E-and N-genes (Envelope and Nucleocapsid genes respectively). SpO2 (percentage saturation of oxygen in the blood) was assessed on a daily basis, while inflammatory markers such as Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein, and D-dimer and Neutrophil/Lymphocyte Ratios (NLR), were assessed at baseline and day 7 post treatment. Clinical status was self-assessed daily on a Likert scale. Results: 2-way Repeated measures Analysis of Variance (RMANOVA) did not show any difference between the two groups. However, there was a significant time effect (improvement over time) for SpO2, Ct N-gene, Ct E-gene and clinical status in both groups, and significant reductions in inflammatory markers by day 7 (P < 0.0001). Conclusions: AZT + HCQ may be redundant adjuncts in COVID-19 therapy. Improvements noted are likely due in large part to Ivermectin virucidal and anti-inflammatory actions.
RANdOmisEd dRug TRiAl
Trial ID PACTR202108891693522.
References
Ahmed, Karim, Ross, Hossain, Clemens, A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness, Int J Infect Dis
Ajayi, Drugs shown to inhibit SARS-CoV-2 in COVID-19 disease: Comparative basic and clinical pharmacology of molnupiravir and ivermectin, Austin J Pharmacol Ther
Andreani, Bideau, Duflot, Jardot, Rolland et al., In vitro testing of combined References
Annunziata, Coppola, Carannante, Simioli, Lanza, Home management of patients with moderate or severe respiratory failure secondary to
Babalola, Bode, Ajayi, Alakaloko, Akase, Ivermectin shows clinical benefits in mild to moderate COVID19: A randomized controlled double-blind, dose-response study in Lagos, QJM
Boulware, Pullen, Bangdiwala, Pastick, Lofgren, A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19, N Engl J Med,
doi:10.1056/nejmoa2016638Bryant, Lawrie, Dowswell, Fordham, Mitchell, Ivermectin for prevention and treatment of COVID-19 infection: A systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines, Am J Ther
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res
Damle, Vourvahis, Wang, Leaney, Corrigan, Clinical pharmacology perspectives on the antiviral activity of azithromycin and use in COVID-19, Clin Pharmacol Ther
Gautret, Lagier, Parola, Hoang, Meddeb, Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Hill, Garratt, Levi, Falconer, Ellis, Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection, Open Forum Infectious Diseases,
doi:10.1093/ofid/ofab358/6316214Hoffmann, Mösbauer, Hofmann-Winkle, Kaul, Kleine-Weber, Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, Nature
Hooks, Bart, Vardeny, Westanmo, Adabaq, Effects of hydroxychloroquine treatment on QT interval, Heart Rhythm
Horby, Mafham, Linsell, Bell, Staplin, Effect of hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2022926Kashour, Riaz, Garbati, Aldosary, Tlayjeh, Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: A systematic review and metaanalysis, J Antimicrob Chemother
Kory, Gianfranco, Varon, Iglesias, Marik, Review of the emerging evidence demonstrating the efficacy of ivermectin in the prophylaxis and treatment of COVID-19, Am J Ther
Li, Wang, Agostinis, Rabson, Melino, Is hydroxychloroquine beneficial for COVID-19 patients?, Cell Death Dis
Maisonnasse, Guedj, Contreras, Behillil, Solas, Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates, Nature
Osman, Farouk, Osman, Abdrabou, Longitudinal assessment of chest computerized tomography and oxygen saturation for patients with COVID-19, The Egyptian Journal of Radiology and Nuclear Medicine
Portmann-Baracco, Alberti, Accinelli, Antiviral and anti-inflammatory properties of Ivermectin and its potential use in COVID-19, Arch Bronconeumol
Poschet, Perkett, Timmins, Deretic, Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells, BioRxiv
Raoult, Hsueh, Stefani, Rolain, COVID-19 therapeutic and prevention, Int J Antimicrob Agents
Shah, Drug-induced QT interval prolongation: Does ethnicity of the thorough QT study population matter?, Br J Clin Pharmacol
Touret, Gillesm, Barral, Nougairède, Van Helden, In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication, Sci Rep
Weston, Coleman, Haupt, Logue, Matthews, Broad anti-coronaviral activity of food and drug administration approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo, J Virol
Who, Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus
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