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| Name | Class |
|---|---|
| Mahidol Oxford Tropical Medicine Research Unit | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arterolane-piperaquine | Active Comparator | Arterolane-piperaquine for 3 days |
|
| Arterolane-piperaquine+mefloquine | Active Comparator | Arterolane-piperaquine + mefloquine for 3 days |
|
| Artemether-lumefantrine | Active Comparator | Artemether-lumefantrine for 3 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Arterolane-piperaquine | Drug | Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm | 42 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Parasite reduction rates | Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy |
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Inclusion Criteria:
Male or female aged 2 years to <13-year-old
Uncomplicated falciparum malaria as defined as:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kilifi County Hospital | Kilifi | P.O Box P.O. Box 9 | Kenya |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34111412 | Derived | Hamaluba M, van der Pluijm RW, Weya J, Njuguna P, Ngama M, Kalume P, Mwambingu G, Ngetsa C, Wambua J, Boga M, Mturi N, Lal AA, Khuroo A, Taylor WRJ, Goncalves S, Miotto O, Dhorda M, Mutinda B, Mukaka M, Waithira N, Hoglund RM, Imwong M, Tarning J, Day NPJ, White NJ, Bejon P, Dondorp AM. Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2021 Oct;21(10):1395-1406. doi: 10.1016/S1473-3099(20)30929-4. Epub 2021 Jun 7. |
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Anonymized data will be entered to a database maintained by Mahidol-Oxford-Research-Unit. Individual-level anonymized data will be shared with medical regulators where appropriate. For wider stake-holder engagement and the medical community summary-level statistical analyses will be shared. Information collected or generated during this study may be anonymised for use to support new research and policies for antimalarial drug resistance. Any future research using information from this study must first be approved by a local or national expert committee to make sure that the interests of participants and their communities are protected.
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randomised 1:1:1 to one of the three treatment arms
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| Arterolane-piperaquine+mefloquine | Drug | Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) Mefloquine tablets (250 mg) |
|
| Artemether-lumefantrine | Drug | Artemether-lumefantrine tablets (20 mg/120 mg) |
|
| 24 and 48 hours |
| Parasite count to fall 50% | Time for parasite count to fall 50% of initial parasite density | 42 days |
| Parasite count to fall 90% | Time for parasite count to fall 90% of initial parasite density | 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 | 42 days |
| Incidence of clinical adverse events and serious adverse events | 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 | 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 | 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 | 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 | 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 | 42 days |
| Prevalence of Kelch13 mutations of known significance | Prevalence of Kelch13 mutations of known significance | 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 | Baseline |
| Genome wide association with in vivo/in vitro sensitivity parasite phenotype | Genome wide association with in vivo/in vitro sensitivity parasite phenotype | 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 | Baseline and 6 hours |
| Proportion of patients with gametocytaemia before, during and after treatment | Proportion of patients with gametocytaemia before, during and after treatment | 42 days |
| Levels of RNA transcription coding for male or female gametocytes | Levels of RNA transcription coding for male or female gametocytes at admission | Baseline |
| In vitro sensitivity of P. falciparum to artemisinins and partner drugs | 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 | 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 | 7 days |
| Data on recent travel and current location of living | Baseline |
| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
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| ID | Term |
|---|---|
| D000077611 | Artemether, Lumefantrine Drug Combination |
| ID | Term |
|---|---|
| D000077549 | Artemether |
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
| D009930 | Organic Chemicals |
| D000078102 | Lumefantrine |
| D005449 | Fluorenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
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