Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study

NCT ID: NCT02509481

Last Updated: 2019-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 2712 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2015-12-31

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

Conditions

Malaria; Lymphatic Filariasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Single MDA

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Group Type: ACTIVE_COMPARATOR

Ivermectin

Intervention Type: DRUG

Albendazole

Intervention Type: DRUG

Repeated MDA

Same at Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Group Type: EXPERIMENTAL

Ivermectin

Intervention Type: DRUG

Albendazole

Intervention Type: DRUG

Interventions

Ivermectin

Intervention Type: DRUG

Albendazole

Intervention Type: DRUG

Other Intervention Names

Mectizan

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut de Recherche en Sciences de la Sante, Burkina Faso

OTHER_GOV

Sponsor Role: collaborator

Centre Muraz

OTHER

Sponsor Role: collaborator

Ministère de la Santé du Burkina Faso

UNKNOWN

Sponsor Role: collaborator

Colorado State University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian D. Foy, PhD

Role: PRINCIPAL_INVESTIGATOR

Colorado State University

Roch K Dabire, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute de Recherche en Sciences de la Santé

Locations

Colorado State University

Fort Collins, Colorado, United States

Institut de Recherche en Sciences de la Santé

Bobo-Dioulasso, Houet, Burkina Faso

Countries

United States; Burkina Faso

References

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.

Reference Type: DERIVED

PMID: 30878222 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

OPP1116536

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

5375011

Identifier Type: -

Identifier Source: org_study_id