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Completed

NCT Number: NCT03452475

Comparison of Arterolane-piperaquine Versus Arterolane-piperaquine+Mefloquine Versus Artemether-lumefantrine in Kenyan Children

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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Key information

Conditions

Plasmodium Falciparum Infections Malaria Malaria, Falciparum Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

2 year–12 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Kilifi County Hospital

Kilifi, P.O Box P.O. Box 9, Kenya

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Arterolane-piperaquine

Drug

Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg)

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)

Primary outcomes

  1. 42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm

    Time frame: 42 days

Secondary outcomes

  1. Parasite clearance half-life

    Time frame: 42 days

    Parasite clearance half-life is assessed by entering the parasite counts (assessed by microscopy) in the WWARN PCE calculator

  2. Parasite reduction rates

    Time frame: 24 and 48 hours

    Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy

  3. Parasite count to fall 50%

    Time frame: 42 days

    Time for parasite count to fall 50% of initial parasite density

  4. Parasite count to fall 90%

    Time frame: 42 days

    Time for parasite count to fall 90% of initial parasite density

  5. Fever clearance time

    Time frame: 42 days

    The time taken for the tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours

  6. Incidence of clinical adverse events and serious adverse events

    Time frame: 42 days

  7. Incidence of adverse events concerning markers of hepatic or renal toxicity

    Time frame: 42 days

    Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured

  8. Incidence of prolongation of the corrected QT interval

    Time frame: 42 days

    Incidence of the prolongation of the corrected QT interval above 500 ms or > 60 ms above baseline values

  9. Prolongation of the corrected QT interval

    Time frame: 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

  10. Change in haematocrit

    Time frame: 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

  11. Proportion of patients that reports completing a full course of observed TACT or ACT

    Time frame: 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

  12. Prevalence of Kelch13 mutations of known significance

    Time frame: Baseline

    Prevalence of Kelch13 mutations of known significance

  13. 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

    Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations

  14. Genome wide association with in vivo/in vitro sensitivity parasite phenotype

    Time frame: Baseline

    Genome wide association with in vivo/in vitro sensitivity parasite phenotype

  15. A comparison of transcriptomic patterns between sensitive and resistant parasites

    Time frame: Baseline and 6 hours

    Transcriptomic patterns measure at baseline and at specified time points after the start of treatment comparing sensitive and resistant parasites

  16. Proportion of patients with gametocytaemia before, during and after treatment

    Time frame: 42 days

    Proportion of patients with gametocytaemia before, during and after treatment

  17. Levels of RNA transcription coding for male or female gametocytes

    Time frame: Baseline

    Levels of RNA transcription coding for male or female gametocytes at admission

  18. In vitro sensitivity of P. falciparum to artemisinins and partner drugs

    Time frame: Baseline and day recurrent infection

  19. Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs

    Time frame: 42 days

    Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs

  20. Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm

    Time frame: 7 days

    Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm

  21. Data on recent travel and current location of living

    Time frame: Baseline

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Collaborators

  • Mahidol Oxford Tropical Medicine Research Unit

Registry information

Official study title

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

Acronym: TACTKenya

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Mar 2, 2018
Registry last updated
Sep 29, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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