NCT03452475CompletedPhase 3
An Open-label Randomised Trial to Assess the Therapeutic Efficacy and Tolerability of Arterolane-piperaquine Plus Single Low Dose Primaquine Versus Arterolane-piperaquine Plus Mefloquine and Single Low Dose Primaquine Versus Artemether-lumefantrine Plus Single Low Dose Primaquine in the Treatment of Uncomplicated Falciparum Malaria in Children in Kenya
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- University of Oxford
- Enrollment
- 219
- Locations
- 1
- Primary Endpoint
- 42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 2 Years to 12 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Arterolane-piperaquine
Active Comparator
Arterolane-piperaquine for 3 days
Intervention: Arterolane-piperaquine (Drug)
Arterolane-piperaquine+mefloquine
Active Comparator
Arterolane-piperaquine + mefloquine for 3 days
Intervention: Arterolane-piperaquine+mefloquine (Drug)
Artemether-lumefantrine
Active Comparator
Artemether-lumefantrine for 3 days
Intervention: Artemether-lumefantrine (Drug)
Outcomes
Primary Outcomes
42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm
Time Frame: 42 days
Secondary Outcomes
- Parasite clearance half-life(42 days)
- Genome wide association with in vivo/in vitro sensitivity parasite phenotype(Baseline)
- Data on recent travel and current location of living(Baseline)
- Incidence of adverse events concerning markers of hepatic or renal toxicity(42 days)
- Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs(42 days)
- Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm(7 days)
- Incidence of prolongation of the corrected QT interval(42 days)
- Prolongation of the corrected QT interval(Baseline, hour 4, hour 24, hour 28, hour 48 and hour 52)
- Change in haematocrit(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(42 days)
- A comparison of transcriptomic patterns between sensitive and resistant parasites(Baseline and 6 hours)
- Proportion of patients with gametocytaemia before, during and after treatment(42 days)
- Levels of RNA transcription coding for male or female gametocytes(Baseline)
- Parasite count to fall 50%(42 days)
- Fever clearance time(42 days)
- 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)
- In vitro sensitivity of P. falciparum to artemisinins and partner drugs(Baseline and day recurrent infection)
- Parasite reduction rates(24 and 48 hours)
- Parasite count to fall 90%(42 days)
- Prevalence of Kelch13 mutations of known significance(Baseline)
Investigators
Study Sites (1)
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