Ivermectin Therapy for Scabies Infection in Children Younger Than 5 Years of Age (ITCHY Study) (ITCHY)

This is an open label prospective pharmacokinetic single arm study in Laos PDR. This study will be embedded within a cluster-randomized controlled trial of interventions to address childhood undernutrition (SUANHOAM Trial, ACTRN12620000520932) and involves a collaboration with the Murdoch Children's Research Institute, Burnet institute and Lao Tropical and Public Health Institute. The primary objective is to determine in young children aged 2 to <5 years and weighing 10 to <15 kg if an ivermectin dose of 3 mg achieves comparable drug exposures to the recommended dose in older children. It aims to provide reliable evidence for a safe and effective dose of ivermectin in young children who are especially vulnerable to scabies infections and the associated secondary complications.

Children aged 2 to <5years and weighing 10 to <15 kg with clinically diagnosed scabies infection in the participating sites in Laos PDR will be approached for recruitment into the study if eligible (see eligibility criteria) and allocated into one of four blood sampling groups with 25 participants in each group. The 3mg dose of ivermectin will be administered orally and blood samples will be collected at two different time points accordingly to blood sampling groups allocation after the first 3mg dose of ivermectin. Clinical responses will be assessed on day 14. A second dose of ivermectin to complete the treatment will only be administered if the first dose has been tolerated by the participants. The 3mg ivermectin drug exposure, safety and effectiveness will be measured.

All participants will receive one dose of oral ivermectin 3mg on day 0 and have two blood samples taken to determine the serum ivermectin concentrations after the dose. Timing of blood samples will vary depending on the allocated group.

The mean (standard deviation) of ivermectin exposure as measured by the area under the concentration-time curve (AUC0) in the study population of children aged 2 to <5 years and weighing 10 to <15 kg. The calculated AUC will be AUC0- ∞ i.e. from time 0 extrapolated to infinity for a single dose. Comparable drug exposure will be defined as the mean ivermectin AUC in the study population being ≥80% (efficacy boundary) and ≤125% (toxicity boundary) of the mean AUC in the children aged ≥5 years and weighing ≥15 kg from our previous study with 90% confidence Intervals.

Causality will be assessed using the Naranjo Adverse Drug Reaction Probability Scale Worksheet. The Naranjo Algorithm, or Adverse Drug Reaction Probability Scale, is a method by which to assess whether there is a causal relationship between an identified untoward clinical event and a drug using a questionnaire to assign probability scores.

The proportion of children whose scabies infection has improved at 14 days as assessed by the same treating clinician as on day 0. The severity of scabies infection will be measured using a descriptive scale (No Change, Improved -Completely resolved, improved-partially resolved, worsened, other, unknown) , the outcome will be presented as descriptive data (i.e percentage of participants in each category of the scale )

Inclusion Criteria: Children aged 2 to <5 years and weighing 10 to <15 kg with scabies infection as clinically diagnosed by the treating clinician. Exclusion Criteria: Children with known liver disease Children with known allergy to ivermectin Children with concomitant warfarin use Children with known neurological disease Children already receiving topical treatment for scabies

The de-identified data set collected for the analysis of the ITCHY trial will be available six months after publication of the primary outcome.

Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the ITCHY Trial Principle and Associate Investigators must see and approve the analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.