This open-label randomised controlled clinical trial will compare the safety, tolerability, therapeutic efficacy and pharmacokinetics and pharmacodynamics of arterolane-piperaquine, arterolane-piperaquine plus mefloquine versus artemether-lumefantrine.in children with uncomplicated falciparum malaria in Kilifi, Kenya. This study will also provide an up to date insight on the current presence of antimalarial resistance in this site. In addition, all children will be treated with a single low dose of primaquine, dosing is age based. The investigators will recruit 219 patients aged 2 years to 12 years with acute uncomplicated falciparum malaria in Kilifi County Hospital.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
219
Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg)
Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) Mefloquine tablets (250 mg)
Artemether-lumefantrine tablets (20 mg/120 mg)
Kilifi County Hospital
Kilifi, Kenya
42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm
Time frame: 42 days
Parasite clearance half-life
Parasite clearance half-life is assessed by entering the parasite counts (assessed by microscopy) in the WWARN PCE calculator
Time frame: 42 days
Parasite reduction rates
Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy
Time frame: 24 and 48 hours
Parasite count to fall 50%
Time for parasite count to fall 50% of initial parasite density
Time frame: 42 days
Parasite count to fall 90%
Time for parasite count to fall 90% of initial parasite density
Time frame: 42 days
Fever clearance time
The time taken for the tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours
Time frame: 42 days
Incidence of clinical adverse events and serious adverse events
Time frame: 42 days
Incidence of adverse events concerning markers of hepatic or renal toxicity
Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured
Time frame: 42 days
Incidence of prolongation of the corrected QT interval
Incidence of the prolongation of the corrected QT interval above 500 ms or \> 60 ms above baseline values
Time frame: 42 days
Prolongation of the corrected QT interval
Prolongation of the corrected QT interval compared at hour 4, hour 24, hour 28, hour 48 and hour 52 compared to baseline
Time frame: Baseline, hour 4, hour 24, hour 28, hour 48 and hour 52
Change in haematocrit
Change in haematocrit at hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42 according to geographical location and study arm, stratified for G6PD status
Time frame: Baseline, hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42
Proportion of patients that reports completing a full course of observed TACT or ACT
Proportion of patients that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study because of drug related serious adverse event
Time frame: 42 days
Prevalence of Kelch13 mutations of known significance
Prevalence of Kelch13 mutations of known significance
Time frame: Baseline
Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations
Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations
Time frame: Baseline
Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Time frame: Baseline
A comparison of transcriptomic patterns between sensitive and resistant parasites
Transcriptomic patterns measure at baseline and at specified time points after the start of treatment comparing sensitive and resistant parasites
Time frame: Baseline and 6 hours
Proportion of patients with gametocytaemia before, during and after treatment
Proportion of patients with gametocytaemia before, during and after treatment
Time frame: 42 days
Levels of RNA transcription coding for male or female gametocytes
Levels of RNA transcription coding for male or female gametocytes at admission
Time frame: Baseline
In vitro sensitivity of P. falciparum to artemisinins and partner drugs
Time frame: Baseline and day recurrent infection
Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs
Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs
Time frame: 42 days
Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm
Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm
Time frame: 7 days
Data on recent travel and current location of living
Time frame: Baseline
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