Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity

Papua New Guinea Institute of Medical Research

Status and phase: Completed; Phase 4

Conditions: Plasmodium Vivax Clinical Episode; Plasmodium Vivax Infection; Plasmodium Falciparum Infection; Plasmodium Falciparum Clinical Episode

Treatments: Drug: Placebo; Drug: Artemether Lumefantrine; Drug: Primaquine; Drug: Chloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT02143934

07200734

Details and patient eligibility

About

This study specifically seeks to quantify the contribution of relapes to the burden of P. vivax infections and disease by determining on the effect of radical pre-erythrocytic and erythrocytic clearance on subsequent rates of Plasmodium spp. infection and disease in children aged 5-10 years in a treatment to re-infection study design. In order the clear liver-stage/blood-stages G6PD-normal children were randomised to receive Chloroquine (3 days, standard dose) and Coartem (3 days, standard dose) plus either i) primaquine (20 days, 0.5mg/kg) or ii) placebo (20days). These drugs were administered over a period of 4 weeks.

In addition to this epidemiological data, the study will assess the natural acquisition of cellular and humoral immune responses to P. falciparum and P. vivax, thus assisting in the determination of correlates of clinical immunity to P. falciparum and P. vivax in PNG children aged 5-10 years.

These data will not only be essential for development of future vaccines against P. vivax and P falciparum but provide invaluable insight into the contribution of long-lasting liver-stages to the force of infection with P. vivax that will contribute towards designing more rational approaches to the treatment of P. vivax both in the context of case management and future attempts at elimination.

Enrollment: 524 patients

Sex: All

Ages: 5 to 10 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• aged 5-10 years (±3 months)
• permanent residents of the area
• absence of history of hypersensitivity reactions to the drugs

Exclusion criteria

• chronic illness
• severe malnutrition (weight-for-age nutritional Z score [WAZ] <60th percentile)
• severe anemia (Hb <5 g/dL),
• G-6-PD deficiency (<60% G-6-PD activity)
• permanent disability, which prevents or impedes study participation. Any 1 or more of the criteria is sufficient to exclude study participation.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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524 participants in 2 patient groups, including a placebo group

Primaquine

Active Comparator group

Description:

Primaquine, 0.5mg/kg/day, 20 days directly observed treatment Chloroquine, 25mg/kg total dose, divided over 3 days directly observed treatment Artemether-Lumefantrine, 3 days BD

Treatment:

Drug: Primaquine

Drug: Chloroquine

Drug: Artemether Lumefantrine

Placebo

Placebo Comparator group

Description:

Placebo, 20 days directly observed treatment Chloroquine, mg/kg, 3 days directly observed treatment Artemether-Lumefantrine, 3 days BD

Treatment:

Drug: Chloroquine

Drug: Artemether Lumefantrine

Drug: Placebo