In a recent study posted to the medRxiv* preprint server, researchers assessed the impact of ivermectin on the duration of sustained recovery among coronavirus disease 2019 (COVID-19) outpatients.
Background
Despite advancements in treatment for COVID-19, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their subvariants has modified therapeutic choices since monoclonal antibodies lose efficacy. New oral antivirals have been approved for high-risk individuals in high-income nations. However, the efficiency of these antivirals in vaccinated or previously infected individuals remains unknown. The potential of repurposed medications to improve symptoms as well as clinical outcomes in COVID-19 patients is of significant interest.
About the study
In the present study, researchers examined the efficacy of ivermectin compared to a placebo in treating mild to moderate COVID-19 in its early stages.
The team employed a flexible protocol for a placebo-controlled study that allowed participant recruitment in various venues in healthcare systems, virtual means, and the community. Outpatients having mild to moderate SARS-CoV-2 infection and a verified positive SARS-CoV-2 test are enrolled on the platform. By 22 July 2022, 1206 patients had received their study medicine, contributing placebo, or matched placebo. Participants were either recognized by locations or identified themselves by contacting a study hotline or website.
Study personnel evaluated eligibility requirements, such as the age of 30 years or more, COVID-19 within ten days, and the presence of over two acute COVID-19 symptoms within seven or fewer days after enrolment. Symptoms may include body aches, cough, dyspnea, fever, fatigue, nausea, diarrhea, vomiting, headache, chills, nasal symptoms, and loss of taste or smell. The participants were first randomized to receive either the active agent or placebo. The team utilized fluvoxamine, administered 50 mg twice daily for ten days, as the other research drug under evaluation during this period.
Time to sustained recovery, the duration between study drug administration and the third of three consecutive days without any COVID-19 symptoms, was the key indicator of efficacy. The most important secondary result was hospitalization or mortality by day 28. Other secondary objectives were the estimated mean duration of illness from a longitudinal ordinal model, the COVID-19 Clinical Progression Scale on days seven, 14, and 28; death through day 28; and a visit to the emergency department (ED) or urgent care, hospitalization, or mortality through day 28.
Results
Of the 2212 people who were recruited, 1206 individuals were eligible for receiving ivermectin and were randomized to ivermectin, or placebo, and received the study medicine. A total of 543 placebo recipients received a matching placebo, while 61 received the contributing placebo. The participants’ median age was 48 years, among which 46% were 50 years or older. Almost 84% of subjects reported receiving two or more doses of the COVID-19 vaccines.
The median period to recovery was 11 days for the ivermectin and the placebo groups. The posterior probability of benefit concerning the primary result of time to recovery was 0.68, with a hazard ratio (HR) of 1.02, where an HR of more than 1 indicated a faster resolution of symptoms with ivermectin. This posterior probability for the primary outcome was less than the predetermined cutoff of 0.95. The study did not find any benefit of treatment when assessed with a Bayesian non-informative prior, no prior, or when the analysis was restricted to participants who were administered with the study drug two to three days after symptom onset and across different symptom severities as reported on day 1. The team also noted that ivermectin limited the duration of COVID-19 symptoms by 24 hours with less than 0.1% probability.
While hospitalizations and mortalities were rare within the study cohorts, five and two events were noted in the ivermectin and placebo groups, respectively. The secondary composite outcome involving ED or urgent care, hospitalizations, or mortality did not vary between ivermectin and placebo cohorts. The COVID Clinical Progression Scale observed on days seven, 14, and 28 did not reach predetermined treatment thresholds.
In participants who consumed the study medication at least once, adverse events were comparable between the two groups. Cognitive impairment, photosensitivity of the eye, blurred vision, photophobia, vertigo, and asthma were adverse events reported more than twice in the ivermectin group only. Serious adverse events were uncommon, with five reported for ivermectin and three for placebo.
Conclusion
The study findings showed that among a highly vaccinated SARS-CoV-2-infected outpatient cohort, ivermectin therapy for six days versus placebo did not improve the time to recovery. There was no indication of benefit for secondary clinical outcomes, including hospitalization, death, and acute care visits. These results do not support the usage of ivermectin in COVID-19 outpatients.
*Important notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
