Community-led Responses for Elimination: Controlled Trial of Reactive Case Detection Versus Reactive Drug Administration (CORE Zambia)

People Acting To Help (PATH)

Status and phase: Completed; Phase 4

Conditions: Malaria

Treatments: Drug: Reactive Focal Drug Administration

Study type: Interventional

Funder types: Other

Identifiers

NCT02654912

PATH-WIRB-1155095

Details and patient eligibility

About

This study is designed to compare the effectiveness of reactive focal drug administration (RFDA) using dihydroartemisinin+piperaquine (DHAP) versus reactive focal test and treat (RFTAT) using artemether+lumefantrine (AL) as a routine process for identifying and eliminating malaria transmission as measured through achieving zero seropositivity in children under five in Southern Province, Zambia. These two strategies are potential candidates for expanded malaria operational surveillance and elimination for low malaria transmission areas.

Full description

The study is a cluster randomized controlled trial designed to evaluate the impact of RFDA intervention against current standard of care for the impact on seropositivity in children under five years, passive surveillance for confirmed malaria case incidence, and elimination of transmission from hotspots. It will be conducted among a background population of ~130,000 people in ~30,000 households in 16 health center catchment areas across several districts in Southern Province. The government of Zambia is pursuing malaria elimination as a national goal on an accelerated timeline and this trial will help evaluate two treatment-based strategies for supporting malaria elimination.

The secondary objectives of the study include: 1). Compare the effectiveness of RFDA using DHAP with RFTAT using AL in reducing rapid diagnostic test (RDT) confirmed malaria incidence through passive case detection at health facilities; 2). Compare the effectiveness of RFDA using DHAP with RFTAT using AL in reducing the prevalence of malaria and preventing re-infection in individuals receiving reactive responses; 3). Compare the cost-effectiveness of RFDA using DHAP with RFTAT using AL in reducing the burden of malaria in the community; 4). Measure the proportion of P. falciparum infections likely attributable to importation and local transmission using parasite genotyping as well as defining genotype spatial distribution; 5). Assess the utility of using serology to measure short term changes in malaria transmission and evaluate malaria elimination programs; and 6). Assess the feasibility of using remotely sensed malaria risk maps to identify areas with higher potential for local malaria transmission.

Enrollment: 8,682 patients

Sex: All

Ages: 3+ months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• anyone not excluded and consenting

Exclusion criteria

• contraindications from manufacturer for medications including currently taking haloperidol, artane, Phenergan (Promethazine), chlorpromazine, erythromycin, Azithromycin, clarithromycin, Ketoconazole, fluconazole, mefloquine (as prophylaxis), lumefantrine (in Coartem), quinine, Septrin
• anyone seriously ill
• currently taking antimalarial medicines
• allergy to artemisinin drugs
• pregnant women in first trimester
• children under 3 months of age
• reported heart condition

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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8,682 participants in 2 patient groups

Reactive Focal Drug Administration

Experimental group

Description:

This is the experimental arm and is described by a reactive response to passively detected index case of malaria. The reactive response consists of treating all individuals within a defined radius of each RDT-confirmed incident malaria case with dihydroartemisinin-piperaquine (DHAP).

Treatment:

Drug: Reactive Focal Drug Administration

Reactive Focal Test and Treat

No Intervention group

Description:

This is the current standard of care in Southern Province and is described by a reactive response to passively detected index case of malaria. The reactive response consists of testing all individuals within a defined radius of each RDT-confirmed incident malaria case with an RDT and treating all positive individuals with artemether-lumefantrine (AL).