Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose ( n = 12) or placebo ( n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher’s exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19–36 in the ivermectin and 21–44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77–1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 ( p = 0·24 for gene E; p = 0·18 for gene N) and day 7 ( p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment ( p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra.
【저자키워드】 COVID-19, Ivermectin, SARS-CoV-2, Anosmia, Hyposmia, 【초록키워드】 Treatment, Efficacy, Trial, risk, Symptom, in vitro, cough, headache, global health, Randomized, Nasopharyngeal swab, PCR, Viral load, Fever, placebo-controlled trial, Patient, Placebo, SARS-CoV-2 RNA, recruitment, disease, funding, trials, COVID-19 patients, single dose, Evidence, IgG titer, Concentration, dose, severe disease, disease onset, Barcelona, double-blind, Support, reduction, Clinical use, Factor, Enrollment, Primary outcome, no risk, ivermectin group, median age, no difference, primary outcome measure, Registered, malaise, doses, finding, Fisher, transmission of SARS-CoV-2, Administered, replication of SARS-CoV-2, enrolled, evaluate, occurred, proportion, recruited, reported, detectable, inhibit, approved, conducted, receiving, supported, onset of fever, calculated, reduce, receive, 1:1, PCR positive patient, 【제목키워드】 randomized clinical trial, Symptom, Viral load, early treatment, Patient, placebo-controlled, double-blind, humoral,