Clinical trial NCT02509481: Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study
Official title: Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Malaria
Lymphatic Filariasis
Keywords: malaria
lymphatic filariasis
mosquito
ivermectin
mass drug administration
Lead sponsor: Colorado State University
Sponsor class: OTHER
Collaborators: name: Institut de Recherche en Sciences de la Sante, Burkina Faso
name: Centre Muraz
name: Ministère de la Santé du Burkina Faso
First posted: 2015-07-28
Enrollment: 2712
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether repeated ivermectin mass drug administrations to Burkinabé villagers, performed in three week intervals over the rainy-season, is well-tolerated and safe, and also effective in reducing local malaria transmission and thus clinical malaria episodes in treated village children.

Detailed description: Primary Objective: To determine the efficacy of repeated ivermectin mass drug administrations (IVM MDA) (150 µg/kg), given to the population of eligible patients in enrolled villages, for reducing the cumulative incidence of uncomplicated malaria episodes in enrolled village children (≤ 5 years of age) over the course of the treatment.

Hypothesis: Repeated IVM MDA starting at the beginning of the rainy season will be well tolerated and safe, and will reduce clinical malaria episodes in children by significantly reducing malaria transmission among treated villages.

Overview Study Design: Single-blind (outcomes assessor); parallel assignment with 2 arms; cluster-randomized control trial to determine the effect of repeated IVM MDA on malaria transmission and clinical malaria episodes. The unit of randomization will be the village (cluster). 8 villages total will be enrolled in two arms. The active comparator arm (4 villages) will receive a single standard MDA (IVM; 150-200 µg/kg + albendazole; 400 mg) soon after the start of the rainy season, while the experimental arm (4 villages) will receive the standard MDA on the same date, plus 5 more IVM MDA at 3 week intervals thereafter. The primary endpoint will be the cumulative incidence of clinical malaria episodes in children ≤5 year of age within each village.

Sites: This study will be conducted in villages along the main east-west and north-south road corridors in the Sud-Ouest administrative region of Burkina Faso.

Study Population: Indigenous Burkinabé from various ethnic groups (Dagara, Bobo, Lobi, Mossi, etc.). The entire eligible population of each enrolled village will receive the MDAs, following the standard inclusion/exclusion criteria of MDA for control of microfilaremia caused by Wuchereria bancrofti (lymphatic filariasis; LF). Clinical incidence of malaria will be assessed only in children living in enrolled villages who are ≤ 5 years of age, most of whom will not have received any treatment due to the standard MDA exclusion criteria of children \< 90 cm.

Study Interventions: 2 arms: 1) Active comparator arm - single standard MDA with IVM (150 µg/kg) + albendazole (ALB;400 mg) soon after the beginning of the rainy season; 2) Experimental arm, single standard MDA with IVM (150 µg/kg) + ALB (400 mg) plus 5 more MDA with IVM alone (150 µg/kg) at 3 week intervals thereafter. Community health workers and trained by local health authority of the Sud-Ouest region will perform the first MDA in both arms with logistical assistance from the study investigators. Repeated MDAs will only occur in the experimental-arm villages, and be performed by the study investigators.

Follow-up Procedures: Trained nurses will visit each study village each week over the course of the study to investigate and record any adverse events or severe adverse events communicated by the study population. They will also perform active case surveillance each week on enrolled village children for clinical malaria episodes, defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum. Secondary measures will be collected by the nurses.

Sample Size: Assuming an 80% cumulative incidence of malaria episodes in the control arm and an intracluster correlation coefficient of 0.02, 4 clusters are needed per arm and 69 children enrolled per cluster to detect a conservative 40% reduction in incidence in the treatment arm with 80% power and a statistical confidence of 95%.

Safety Outcomes:

• Adverse events (seriousness, causality, expectedness)

Secondary Outcomes:

* Incidence of new P. falciparum infections acquired (molecular force-of-infection)
* Prevalence and intensity (eggs/larvae per gram of feces) of soil transmitted helminth infections in a subset of treated patients between 6-10 years of age.
* Indoor-resting Anopheles mosquito capture rate
* Outdoor-host seeking Anopheles mosquito capture rate
* Adult mosquito age structure (parity rate) in captured mosquitoes
* Plasmodium sporozoite rate/entomological inoculation rate in captured mosquitoes
* Rate of Wuchereria bancrofti in captured mosquitoes

Eligibility criteria: Inclusion Criteria:

* Residence in the study site
* Able to understand the information and willing to give consent and assent (parent or guardian consent if study participant age is \< 18 years)

Exclusion Criteria:

* Residence outside of in the study site
* Height ≤ 90 cm
* Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension
* Pregnancy
* Breast feeding if infant is within 1 week of birth
* Known allergy to the study drugs

Primary outcomes:
measure: Incidence of Clinical Malaria Episodes
timeFrame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Secondary outcomes:
measure: Adverse Events
timeFrame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
measure: Entomological Indicator of Parasite Transmission
timeFrame: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
measure: Molecular Force of P. Falciparum Infection
timeFrame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
measure: Number of 6-10 Year Old Participants With Soil Transmitted Helminths (STH)
timeFrame: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
measure: Entomological Inoculation Rate
timeFrame: 6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: Colorado State University
state: Colorado
city: Bobo Dioulasso
country: Burkina Faso
facility: Institut de Recherche en Sciences de la Santé
state: Houet
Study officials:
affiliation: Colorado State University
name: Brian D. Foy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute de Recherche en Sciences de la Santé
name: Roch K Dabire, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Foy BD, Alout H, Seaman JA, Rao S, Magalhaes T, Wade M, Parikh S, Soma DD, Sagna AB, Fournet F, Slater HC, Bougma R, Drabo F, Diabate A, Coulidiaty AGV, Rouamba N, Dabire RK. Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial. Lancet. 2019 Apr 13;393(10180):1517-1526. doi: 10.1016/S0140-6736(18)32321-3. Epub 2019 Mar 14.