Replication data for Safety and efficacy of 3- and 5-day regimens of levamisole in loiasis: a randomized, placebo-controlled, double-blind clinical trial

Background. Individuals with high Loa loa microfilarial densities (MFD) risk serious adverse events (SAEs) following ivermectin treatment. A single dose of levamisole (LEV) induces a temporary, progressive MFD decrease. We assessed the safety and efficacy of 3- and 5-day LEV (LEV-3 and LEV-5) regimens for loiasis treatment. Methods. A double-blind, randomized, placebo-controlled clinical trial in the Republic of the Congo assigned participants (1:1:1) to receive PLA, LEV-3 or LEV-5. Sample size calculation was based on data from a previous clinical trial evaluating LEV efficacy on L. loa MFD. Safety (occurrence of SAEs, frequency of AEs) was analysed using Fischer’s exact test and logistic regression. Efficacy (MFD reduction and proportion of individuals achieving 40% reduction) was assessed through non parametric tests, adjusted for multiple comparisons. A mixed-effects linear model evaluated MFD changes, with post hoc contrasts. Results. No SAEs occurred, and AE grade severity was similar across arms. Compared with PLA (n=30), LEV-3 (n=33) and LEV-5 (n=28) showed greater MFD reductions on D5 (-1.6, 29.3, and 51.4%, respectively; P<0.001) and a higher proportion of participants acheiving ≥40% MFD reduction on D7 (26.7%, 42.4%, and 64.3% in the PLA, LEV-3, and LEV-5 arms, respectively; P=0.048). From contrasts, LEV-5 reported significant higher MFD reduction compared to LEV-3. Conclusions. A 5-day course of LEV appears to be a safe and relatively effective option for the individualised management of patients with high L. loa MFD. Further studies are needed to explore its potential role as an alternative treatment strategy for onchocerciasis control in areas where onchocerciasis is hypoendemic and loiasis coendemic.