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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03452475
Other study ID # MAL17009
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date March 7, 2018
Est. completion date June 3, 2019

Study information

Verified date September 2021
Source University of Oxford
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 219
Est. completion date June 3, 2019
Est. primary completion date June 3, 2019
Accepts healthy volunteers No
Gender All
Age group 2 Years to 12 Years
Eligibility Inclusion Criteria: 1. Male or female aged 2 years to <13-year-old 2. 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 3. Ability to take oral medication 4. Willingness and ability to comply with study protocol for study duration 5. Written informed consent given to participate in the trial Exclusion Criteria: 1. Signs of severe/complicated malaria* 2. 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. 3. Acute illness other than malaria requiring urgent systemic treatment as assessed by the treating physician 4. Previous splenectomy 5. Treatment with artemisinin or ACT within the previous 7 days 6. Treatment with mefloquine in the 2 months prior to presentation 7. Known hypersensitivity or contraindication to arterolane-piperaquine, DHA-piperaquine, artemisinin, mefloquine (epilepsy, major psychiatric illness) or primaquine 8. QTc interval >450 milliseconds at point of presentation 9. Known personal or family history of cardiac conduction problems 10. Participation within another clinical trial in the previous 3 months

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Arterolane-piperaquine
Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg)
Arterolane-piperaquine+mefloquine
Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) Mefloquine tablets (250 mg)
Artemether-lumefantrine
Artemether-lumefantrine tablets (20 mg/120 mg)

Locations

Country Name City State
Kenya Kilifi County Hospital Kilifi

Sponsors (2)

Lead Sponsor Collaborator
University of Oxford Mahidol Oxford Tropical Medicine Research Unit

Country where clinical trial is conducted

Kenya, 

Outcome

Type Measure Description Time frame Safety issue
Primary 42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm 42 days
Secondary Parasite clearance half-life Parasite clearance half-life is assessed by entering the parasite counts (assessed by microscopy) in the WWARN PCE calculator 42 days
Secondary Parasite reduction rates Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy 24 and 48 hours
Secondary Parasite count to fall 50% Time for parasite count to fall 50% of initial parasite density 42 days
Secondary Parasite count to fall 90% Time for parasite count to fall 90% of initial parasite density 42 days
Secondary Fever clearance time The time taken for the tympanic temperature to fall below 37.5°C and remain there for at least 24 hours 42 days
Secondary Incidence of clinical adverse events and serious adverse events 42 days
Secondary Incidence of adverse events concerning markers of hepatic or renal toxicity Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured 42 days
Secondary 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 42 days
Secondary 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 Baseline, hour 4, hour 24, hour 28, hour 48 and hour 52
Secondary 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 Baseline, hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42
Secondary 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 42 days
Secondary Prevalence of Kelch13 mutations of known significance Prevalence of Kelch13 mutations of known significance Baseline
Secondary 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 Baseline
Secondary Genome wide association with in vivo/in vitro sensitivity parasite phenotype Genome wide association with in vivo/in vitro sensitivity parasite phenotype Baseline
Secondary 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 Baseline and 6 hours
Secondary Proportion of patients with gametocytaemia before, during and after treatment Proportion of patients with gametocytaemia before, during and after treatment 42 days
Secondary Levels of RNA transcription coding for male or female gametocytes Levels of RNA transcription coding for male or female gametocytes at admission Baseline
Secondary In vitro sensitivity of P. falciparum to artemisinins and partner drugs Baseline and day recurrent infection
Secondary Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs 42 days
Secondary 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 7 days
Secondary Data on recent travel and current location of living Baseline
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