None listed
Conditions
Brief summary
This project is a clinical trial designed to answer a specific question regarding the possibility that a drug-drug interaction (DDI) between two commonly used treatments for malaria may compromise effectiveness of curing the now dominant species causing malaria in the Solomon Islands, Plasmodium vivax. This hypothesis is supported by existing knowledge regarding the biology of how these drugs work and by observations that cure rates for vivax malaria are very low in other South Pacific countries (like Vanuatu) that are using the same drug combinations as in the Solomon Islands. The research is intended to help decide on the most effective malaria treatment to use in the Solomon Islands and this question has fundamental importance to strategies for eliminating malaria in the Solomon Islands and the other malaria-endemic countries of the Melanesian South Pacific. The research will be a randomized controlled clinical trial (RCT) of patients with clinical P.vivax infection in the Solomon Islands. It will compare the radical curative efficacy of the drug primaquine (PQ) when co-administered with the current standard treatment of malaria in the Solomons, artemether-lumevantrine (AL) versus PQ co-administered with an alternative malaria treatment (dihydroartemisinin-piperaquine (DP). The research will be conducted in the Tetere region by enrolling patients (both adults and children) through local health centres who are sick with vivax malaria (both male and female, aged 1 and over). Inclusion criteria will include a positive diagnosis of vivax malaria. Exclusion criteria will include infancy (aged <1), pregnancy, a positive G6PD test (performed on all prospective participants – a positive test indicates susceptibility to drug side-effects) and inability or refusal to provide informed written consent.
Interventions
AL+PQ (Arm 1): Artemether-lumefantrine (2/12mg/kg) administered orally with milk twice daily for 3 days (3 morning doses directly observed by research worker, 3 evening doses self administered with adherence checked by packet return) + primaquine (0.25mg/kg) administered orally once daily with food (savory biscuit) for 14 days (co-administered with morning dose of artemether-lumefantrine under direct supervision of research worker on days 0, 1 and 2, administered on its own under observation of
AL+PQ (Arm 1): Artemether-lumefantrine (2/12mg/kg) administered orally with milk twice daily for 3 days (3 morning doses directly observed by research worker, 3 evening doses self administered with adherence checked by packet return) + primaquine (0.25mg/kg) administered orally once daily with food (savory biscuit) for 14 days (co-administered with morning dose of artemether-lumefantrine under direct supervision of research worker on days 0, 1 and 2, administered on its own under observation of community worker on days 4, 5, 6, 8, 9, 11, 12, 13 and administered on its own under supervision of research worker on days 7, and 10. On day 14 research worker will document adherence with full 14 day course by reviewing records of community observers. DP+PQ (Arm 2): Dihydroartemisinin-piperaquine (2.5/20mg/kg) administered orally once daily without milk in the morning (3 morning doses directly observed by research worker) + primaquine (0.25mg/kg) administered orally once daily with food (savory biscuit) for 14 days (co-administered with dose of dihydroartemisinin-piperaquine under direct supervision of research worker on days 0, 1 and 2, administered on its own under observation of community worker on days 4, 5, 6, 8, 9, 11, 12, 13 and administered on its own under supervision of research worker on days 7, and 10. On day 14 research worker will document adherence with full 14 day course by reviewing records of community observers.
Sponsors
The Walter and Eliza Hall Institute of Medical Research
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
12 Months to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age over 12 months 2. Weight greater than or equal to 10kg 3. Melanesian background and living in local area 4. Microscopically (based on field microscopy) or RDT confirmed P.vivax regardless of parasite density. Mixed infections (P.falciparum-P.vivax) can be included.
Exclusion criteria
1. Any signs of severe malaria (see WHO definitions) including: impaired consciousness, respiratory distress, severe anaemia (Hb<5), multiple seizures, frequent vomiting/ inability to swallow tablets, prostration, jaundice, hypotension, abnormal bleeding or hypoglycaemia. 2. Clinical evidence of non-malarial illness (such as pneumonia or otitis media) 3. Severe malnutrition (weight-for-age nutritional Z score [WAZ] <60th percentile) 4. Permanent disability, which prevents or impedes study participation. 5. Treatment with PQ in the previous 14 days 6. Residence or planned travel outside the study area during the follow-up period (precluding supervised treatment and follow-up procedures) 7. Known or suspected pregnancy 8. Currently breastfeeding 9. A positive rapid test for G6PD deficiency (Binax (Trademark) or Carestart (Trademark) RDT)
Outcome results
None listed