Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial
Ananda Wijewickrema, Hasini Banneheke, Arunasalam Pathmeswaran, Fathima Wardha Refai, Malika Kauranaratne, Neelika Malavige, Chandima Jeewandara, Mahendra Ekanayake, Dilhar Samaraweera, Dhanusha Thambavita, Priyadarshani Galappatthy
BMC Infectious Diseases, doi:10.1186/s12879-024-09563-y
Background Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19. Trial design and methods A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups.
Results Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 -20,500) with ivermectin (n = 80) and 4,100 copies/ mL (1,000-65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load.
Conclusion Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms.
and 81 (placebo) patients. Table 2 presents the difference in Log 10 viral load (copies/mL) on day 10; the post hoc power is 60%, which is lower than the planned conventional 80%, as we did not achieve the calculated sample size. However, this is unlikely to have affected the findings of this trial as we have observed a significant reduction in the viral load in the ivermectin arm. A proportion of patients did not have day 28 followup clinical information as they were not contactable over the phone after discharge. Since all patients were
Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations Ethics approval and consent to participate Ethics approval was obtained from the Ethics Review Committee of the Faculty of Medicine, University of Colombo (EC-21-EM02). All methods were carried out in accordance with relevant guidelines and regulations stated in the Declaration of Helsinki
Consent for publication Not applicable.
Competing interests The authors declare no competing interests.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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