Comparison of Arterolane-piperaquine Versus Arterolane-piperaquine+Mefloquine Versus Artemether-lumefantrine in Kenyan Children
- Conditions
- Plasmodium Falciparum
- Interventions
- Registration Number
- NCT03452475
- Lead Sponsor
- University of Oxford
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 219
-
Male or female aged 2 years to <13-year-old
-
Uncomplicated falciparum malaria as defined as:
- Positive blood smear with asexual forms of P. falciparum (may be mixed with non-falciparum species)
- Parasitaemia between 5,000-250,000 parasites/µL
- Fever defined as tympanic temperature >37.5°C or history of fever within last 48 hours
-
Ability to take oral medication
-
Willingness and ability to comply with study protocol for study duration
-
Written informed consent given to participate in the trial
- Signs of severe/complicated malaria*
- Any clinical reason suggesting that the child's treatment should be given immediately and not delayed during the transfer to Kilifi County Hospital in the opinion of the treating physician.
- Acute illness other than malaria requiring urgent systemic treatment as assessed by the treating physician
- Previous splenectomy
- Treatment with artemisinin or ACT within the previous 7 days
- Treatment with mefloquine in the 2 months prior to presentation
- Known hypersensitivity or contraindication to arterolane-piperaquine, DHA-piperaquine, artemisinin, mefloquine (epilepsy, major psychiatric illness) or primaquine
- QTc interval >450 milliseconds at point of presentation
- Known personal or family history of cardiac conduction problems
- Participation within another clinical trial in the previous 3 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Artemether-lumefantrine Artemether-lumefantrine Artemether-lumefantrine for 3 days Arterolane-piperaquine+mefloquine Arterolane-piperaquine+mefloquine Arterolane-piperaquine + mefloquine for 3 days Arterolane-piperaquine Arterolane-piperaquine Arterolane-piperaquine for 3 days
- Primary Outcome Measures
Name Time Method 42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm 42 days
- Secondary Outcome Measures
Name Time Method Parasite clearance half-life 42 days Parasite clearance half-life is assessed by entering the parasite counts (assessed by microscopy) in the WWARN PCE calculator
Genome wide association with in vivo/in vitro sensitivity parasite phenotype Baseline Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Data on recent travel and current location of living Baseline Levels of RNA transcription coding for male or female gametocytes Baseline Levels of RNA transcription coding for male or female gametocytes at admission
Incidence of adverse events concerning markers of hepatic or renal toxicity 42 days Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured
Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs 42 days Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs
Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm 7 days Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm
Proportion of patients with gametocytaemia before, during and after treatment 42 days Proportion of patients with gametocytaemia before, during and after treatment
Incidence of prolongation of the corrected QT interval 42 days Incidence of the prolongation of the corrected QT interval above 500 ms or \> 60 ms above baseline values
Prolongation of the corrected QT interval Baseline, hour 4, hour 24, hour 28, hour 48 and hour 52 Prolongation of the corrected QT interval compared at hour 4, hour 24, hour 28, hour 48 and hour 52 compared to baseline
Change in haematocrit Baseline, hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42 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
Proportion of patients that reports completing a full course of observed TACT or ACT 42 days 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
A comparison of transcriptomic patterns between sensitive and resistant parasites Baseline and 6 hours Transcriptomic patterns measure at baseline and at specified time points after the start of treatment comparing sensitive and resistant parasites
Parasite count to fall 50% 42 days Time for parasite count to fall 50% of initial parasite density
Fever clearance time 42 days The time taken for the tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours
Incidence of clinical adverse events and serious adverse events 42 days Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations 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
In vitro sensitivity of P. falciparum to artemisinins and partner drugs Baseline and day recurrent infection Parasite reduction rates 24 and 48 hours Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy
Parasite count to fall 90% 42 days Time for parasite count to fall 90% of initial parasite density
Prevalence of Kelch13 mutations of known significance Baseline Prevalence of Kelch13 mutations of known significance
Trial Locations
- Locations (1)
Kilifi County Hospital
🇰🇪Kilifi, Kenya