NCT03452475

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
219

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Mar 2018

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 1, 2018

Completed
29 days until next milestone

First Posted

Study publicly available on registry

March 2, 2018

Completed
5 days until next milestone

Study Start

First participant enrolled

March 7, 2018

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 3, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 3, 2019

Completed
Last Updated

September 29, 2021

Status Verified

September 1, 2021

Enrollment Period

1.2 years

First QC Date

February 1, 2018

Last Update Submit

September 28, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

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

    42 days

Secondary Outcomes (21)

  • Parasite clearance half-life

    42 days

  • Parasite reduction rates

    24 and 48 hours

  • Parasite count to fall 50%

    42 days

  • Parasite count to fall 90%

    42 days

  • Fever clearance time

    42 days

  • +16 more secondary outcomes

Study Arms (3)

Arterolane-piperaquine

ACTIVE COMPARATOR

Arterolane-piperaquine for 3 days

Drug: Arterolane-piperaquine

Arterolane-piperaquine+mefloquine

ACTIVE COMPARATOR

Arterolane-piperaquine + mefloquine for 3 days

Drug: Arterolane-piperaquine+mefloquine

Artemether-lumefantrine

ACTIVE COMPARATOR

Artemether-lumefantrine for 3 days

Drug: Artemether-lumefantrine

Interventions

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

Arterolane-piperaquine

Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) Mefloquine tablets (250 mg)

Arterolane-piperaquine+mefloquine

Artemether-lumefantrine tablets (20 mg/120 mg)

Artemether-lumefantrine

Eligibility Criteria

Age2 Years - 12 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Kilifi County Hospital

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

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: randomised 1:1:1 to one of the three treatment arms
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2018

First Posted

March 2, 2018

Study Start

March 7, 2018

Primary Completion

June 3, 2019

Study Completion

June 3, 2019

Last Updated

September 29, 2021

Record last verified: 2021-09

Locations