None listed
Conditions
Brief summary
There is a clear need for an abbreviated dosing schedule for primaquine, provided as early as possible to prevent reactivation of latent forms of P. vivax and to clear gametocytes following infection with either Plasmodium species. The purpose of this trial is to advance the treatment of paediatric malaria in areas with intense transmission of multiple Plasmodium species. The proposed studies, to be carried out in north coastal Papua New Guinea (PNG), address these needs through i) a randomised comparative study of early versus delayed primaquine treatment for the prevention of P. vivax and gametocyte carriage in PNG children with uncomplicated malaria, and ii) a pharmacokinetic study to define whether there is a possible pharmacokinetic interaction, via cytochrome P450 2D6 inhibition, between lumefantrine and primaquine. The primary clinical endpoints for superiority and non-inferiority will be the appearance of any P. vivax parasitaemia within 42 days following treatment for uncomplicated malaria. We hypothesise that these studies will demonstrate: i) There is no clinically relevant pharmacokinetic interaction when primaquine is administered directly following treatment with artemether-lumefantrine ii) A short, high-dose primaquine regimen given directly after artemether-lumefantrine is non-inferior to delayed primaquine treatment in the prevention of post-treatment vivax malaria and gametocyte carriage in children with uncomplicated malaria due to either species.
Interventions
Using computer generated randomisation, children will be allocated 1:1 to either treatment Arm 1 or 2 of the study.
Arm 1 (comparator arm): Artemether-lumefantrine: Oral administration as 1.7 mg/kg artemether and 10 mg/kg lumefantrine given twice-daily for 3 days (Day 0 to 2) with food, with oral administration of 1.0 mg/kg primaquine (given as 7 doses every 12 hours over 3.5 days) starting the day following completion of all artemether-lumefantrine doses (Day 3).
Arm 2: Artemether-lumefantrine:
Using computer generated randomisation, children will be allocated 1:1 to either treatment Arm 1 or 2 of the study. Arm 1 (comparator arm): Artemether-lumefantrine: Oral administration as 1.7 mg/kg artemether and 10 mg/kg lumefantrine given twice-daily for 3 days (Day 0 to 2) with food, with oral administration of 1.0 mg/kg primaquine (given as 7 doses every 12 hours over 3.5 days) starting the day following completion of all artemether-lumefantrine doses (Day 3). Arm 2: Artemether-lumefantrine: Oral administration as 1.7 mg/kg artemether and 10 mg/kg lumefantrine given twice-daily for 3 days (Day 0 to 2) with food, with oral administration of 1.0 mg/kg primaquine (given as 7 doses every 12 hours over 3.5 days) starting three weeks after completion of all artemether-lumefantrine doses (Day 24). All treatments will be administered as oral tablets, with combinations of full, half- or quarter-tablets swallowed whole or crushed lightly and given with milk to improve absorption of the lumefantrine component and reduce primaquine adverse effects. All morning doses will be given under direct observation, with evening doses of artemether-lumefantrine and primaquine given to the parents each day to administer at home. Treatment compliance will be demonstrated by pharmacokinetic analysis of Day 7 drug assay samples. For the first 60 children recruited into the trial (pharmacokinetic study subset), all primaquine doses will be administered under direct observation (morning and evening).
Sponsors
The University of Western Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
6 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
i) Children aged 0.5 to 12 years ii) Axillary temperature >37.5 degrees Celcius (or self-reported fever during previous 24 hours) iii) Positive for malaria by on-site microscopy, or rapid diagnostic test, or polymerase chain reaction iv) Have not received a study intervention in the previous 4 weeks v) They have no significant co-morbidity vi) they can attend follow-up assessments over the full duration of the study.
Exclusion criteria
i) Clinical signs or symptoms consistent with severe malaria ii) History of allergy to artemether-lumefantrine or primaquine iii) A proven history of G6PD deficiency iv) Severe malnutrition v) Haemoglobin <50 g/L
Outcome results
None listed