Oral ivermectin versus 5% permethrin cream to treat children and adults with classic scabies: multicenter, assessor-blinded, cluster-randomised clinical trial

OBJECTIVE With regards to the existing controversial data (Cochrane
reviews, network meta-analysis) in classic scabies, to investigate whether
oral ivermectin or topical 5% permethrin clinically cure scabies in index
cases and his/her households. DESIGN Multicenter, assessor-blinded,
cluster-randomised non-inferiority trial with a possible switch to
superiority. SETTING 28 French hospitals between January 2016 and December
2021. PARTICIPANTS Adults and children >15 kg, with
dermoscopy-confirmed scabies—index cases— INTERVENTIONS Index cases were
randomly assigned to either the ivermectin group or permethrin group (1:1
ratio). Each cluster member, defined as each index-case’s household,
received the same treatment as the index case (except for children
<15 kg, all prescribed 5% permethrin). All participants received on
day (D)0 and D10, either oral 200-µg/kg ivermectin or 5% permethrin cream,
applied head-to-toe. MAIN OUTCOME MEASURES Primary outcome was D28
clinical cure of the cluster, i.e., disappearance of scabies clinical
signs/symptoms for all the cluster members. Secondary outcomes included
index-case and individual-level analyses and safety. Blinded
Dermatologists were used as assessors. RESULTS The main analysis included
507 ivermectin-treated participants, comprising 142 index
cases-households, and 568 permethrin-treated participants, comprising 147
index cases-households. Their respective cluster-level cure rates were
71.8% vs. 88.5% (–16.7 percentage-point difference, [95% CI, –26.3 to
–7.1]. Secondary outcome percentage-point differences also showed
ivermectin inferiority to 5% permethrin for index cases** **76.6% vs.
91.5%; –14.9 percentage-point difference [–23.6 to –6.2] and participants:
85.3% vs. 94.2%; –9.2 percentage-point difference [–14.9 to –3.5]),
respectively. Intraclass-correlation coefficients were higher for
permethrin than ivermectin for all clusters (0.68 [0.61 to 0.75]
vs. 0.46 [0.37 to 0.56] and cluster size >1 (0.67
[0.60 to 0.74] vs. 0.47 [0.37 to 0.56]). Cutaneous
adverse events occurred in 11.9% and 15.6% of ivermectin and permethrin
participants, respectively. CONCLUSIONS In this first cluster-randomised
trial in dermoscopy-confirmed classic scabies designed, we did not
demonstrate the non-inferiority of D0+D10 oral ivermectin to 5% permethrin
cream to obtain D28 clinical scabies cures of index cases-households.
Conversely, a statistical superiority of 5% permethrin was shown.