Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA)
- Conditions
- Malaria
- Interventions
- Registration Number
- NCT04966702
- Lead Sponsor
- Barcelona Institute for Global Health
- Brief Summary
The BOHEMIA program consists of a combination of studies organized around a central community prevention mass drug administration protocol and four sub-studies (i.e.; social science, entomology, health economics, and environmental), each written as an individual protocol. The protocol is central but used in two separate, individually powered trials in Mozambique and Kenya. The trials have been powered on the efficacy outcome and designed to meet the requirements of World Health Organization's (WHO) preferred product characteristics (PPC) for endectocides.
- Detailed Description
WHO's PPC states that the desired efficacy of an endectocide as stand-alone insecticide in areas of high to moderate transmission is at least 20% reduction in the incidence of clinical malaria (as primary outcome) and incidence of infection (as secondary outcome) in children under 5 years old (the highest incidence age-group in areas with high-transmission), lasting for at least 1 month following a single regimen. Assessing this effect requires a cluster-randomized design with meticulous follow-up of a cohort of children for efficacy and the whole exposed population for safety outcomes, which is the design selected for the BOHEMIA trials.
Two BOHEMIA cluster randomized trials will be carried out in Mozambique (Southern Africa) and Kenya (Eastern Africa). These sites encompass different transmission dynamics that increase the generalizability of results, namely: (a) a gradient of malaria transmission: moderate in Kenya and very high in Mozambique, (b) different species composition of vector population, (c) different rain patterns and environmental conditions, and (d) different livestock species and human/livestock ratios (in Mozambique).
Population:
Co-primary objectives are determined in different populations. Efficacy is primarily determined in a pediatric active cohort (children under 5 years of age in Mozambique and 5-15 years in Kenya), and safety is determined in anyone who receives the drug. Pregnant women and children under 15 kgs are not eligible for treatment.
Treatment Groups:
Two groups of clusters (three in Mozambique) will be randomized to receive (a) ivermectin in humans, (b) ivermectin in humans + livestock (only in Mozambique), or (c) albendazole control. In Mozambique, the study district will be subject to enhanced passive surveillance for malaria.
Primary Outcome Measure:
The primary outcome measure is proposed as incidence in a six-month period given that ivermectin is a short-acting intervention with \<1% residual drug at 30 days after each dose. Efficacy assessment will continue 4 months post last dose of ivermectin, and this will include analysis of the vector population. We have proposed the appropriate duration of impact evaluation relevant to the biology of the intervention, and geared towards being able to clean the data, lock the database, and conduct the primary efficacy and safety analysis efficiently.
Estimated Duration of Study:
Throughout the study there will be two different groups of participants enrolled, the ones receiving the treatment (\>15 kg) and the ones in the active pediatric cohort for the main outcome of malaria incidence (the ages of highest incidence in each country, under 5 years of age in Mozambique and 5-15 years in Kenya). Each group will participate for different periods of time.
Only the group enrolled in the active pediatric cohort will contribute to the primary efficacy outcome and this group will participate from date of first dose for six months. The group receiving treatment (\>15 kg) will contribute to the primary safety outcome and several secondary outcomes (PK, Neglected Tropical Diseases \[NTDs\]) and this group will participate for four months. Women of child-bearing age will be visited one month after the third dose for a final pregnancy test, any pregnancy occurring during the trial will be followed until birth. The cross-sectional survey will enroll participants of all ages one month after the last Mass Drug Administration (MDA) round.
WHO guidance states that trial design and duration should reflect the nature of the intervention and are left at the discretion of researchers. These trials are robustly powered and are being conducted in moderate to high burden areas, so we believe the risk of failing to find an effect is low and if so, it would throw the utility of the intervention into question.
Advancing the development of this new tool towards implementation in the field can be accomplished in a time frame to contribute to the 2030 Global Technical Strategy (GTS) goals.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48145
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ivermectin human Ivermectin Pill The ivermectin group will receive a single dose of 400 mcg/kg, given once a month for three months. Product to be used is Stromectol (Merck) in Mozambique and Ivermectin 3mg USP (Edenbridge) in Kenya. Ivermectin human and livestock (Mozambique only) Ivermectin Pill The ivermectin group will receive a single dose of 400 mcg/kg, given once a month for three months. Product to be used is Stromectol (Merck). For livestock, locally registered veterinary injectable ivermectin at 1% will be used. Ivermectin human and livestock (Mozambique only) Ivermectin Injectable Product The ivermectin group will receive a single dose of 400 mcg/kg, given once a month for three months. Product to be used is Stromectol (Merck). For livestock, locally registered veterinary injectable ivermectin at 1% will be used. Albendazole Albendazole Pill The albendazole group will receive a single dose of 400 mg, given once a month for three months. Generic products will be used in both countries, the final product will be GMP certified and fully bioequivalent with GSK's Albenza®. Bendex (CIPLA) in Mozambique and G-Abzole (Guilin) in Kenya.
- Primary Outcome Measures
Name Time Method To determine the safety (in humans) and efficacy of ivermectin MDA, administered to humans, or humans and livestock simultaneously (only in Mozambique) for the prevention of malaria. 6 months Safety:
The safety endpoint is determined by anyone who receives the drug.
Rate of adverse events (AEs) and serious adverse events (SAEs) and difference between ivermectin and albendazole.
- Secondary Outcome Measures
Name Time Method To assess the relationship between malaria incidence in children (under 5 years in Mozambique and 5-15 years in Kenya) and community prevalence at the peak of the malaria season. 6 months Prevalence - incidence correlation:
- Malaria prevalence at all ages.To assess the efficacy of the intervention using complementary methods (efficacy). 6 months Multiplicity of infection in all ages one month after the last dose.
To assess the safety of the intervention with complementary methods (safety). 12 months AEs and SAEs by organ system.
To assess the PK of the proposed ivermectin dose/regime in its relationship with efficacy and safety outcomes (efficacy and safety). 72 hours Whole blood concentrations of ivermectin in dried blood spots.
To assess the impact of ivermectin MDA at the proposed regimen on the prevalence of selected ectoparasitic NTDs (efficacy on NTDs and acceptability). 6 months * Serial prevalence of scabies using a simplified version of the algorithm described by Mahe et al.
* Serial prevalence of head lice by visual inspection.
* Serial prevalence of Tunga penetrans via visual inspection of the skin in both feet and applying the Fortaleza scale.
* Serial prevalence and severity of bed bug infestation by direct questions about bedbugs in the house.To assess the relationship between active and passive surveillance for malaria at health facility (only Mozambique). 18 months * Infection incidence in children at community level (active surveillance)
* Infection incidence in children at health facility level (passive surveillance)To assess the accuracy for malaria diagnosis of two the different malaria rapid diagnostic tests (RDTs) used in comparison to Polymerase Chain Reaction (PCR) (Mozambique). 6 months Results correlation between HRP2 and pLDH-based RDTs
To assess the accuracy for malaria diagnosis of two the different malaria rapid diagnostic tests (RDTs) used in comparison to PCR (Mozambique). 6 months Proportion of RDT negative but PCR positive infections
Trial Locations
- Locations (2)
KEMRI
🇰🇪Kwale, Kenya
CISM
🇲🇿Mopeia, Zambezia, Mozambique