NCT05060198

Brief Summary

Artemether-lumefantrine (AL) was adopted as first-line antimalarial therapy in Kenya in 2006, and dihydroartemisinin-piperaquine (DP) as the second-line therapy in 2010. In order to monitor the efficacy and potential development of resistance of Plasmodium falciparum parasites to these two drugs, we will conduct an in-vivo study to monitor the efficacy of these antimalarial therapies. A standardized World Health Organization (WHO) in-vivo efficacy study will be conducted in western Kenya among children 6-59 months of age with symptomatic, uncomplicated malaria visiting the out-patient department of hospitals and/or clinics in western Kenya. In this study, 350 children will be randomly assigned to be treated with either AL or DP. Clinical, parasitologic, and hematologic parameters will be monitored over a 42-day follow-up period. Molecular analysis will be conducted to determine the frequency of markers of antimalarial resistance, and to differentiate recrudescence from reinfection. Results from this antimalarial drug efficacy study will be used to assist the Kenya national malaria control program (NMCP) in evaluating the national malaria treatment policy.

Trial Health

100
On Track

Trial Health Score

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

Enrollment
340

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jun 2016

Longer than P75 for not_applicable

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

Study Start

First participant enrolled

June 17, 2016

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 13, 2017

Completed
3.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2020

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

January 13, 2021

Completed
9 months until next milestone

First Posted

Study publicly available on registry

September 29, 2021

Completed
Last Updated

September 29, 2021

Status Verified

September 1, 2021

Enrollment Period

9 months

First QC Date

January 13, 2021

Last Update Submit

September 27, 2021

Conditions

Malaria,Falciparum

Keywords

MalariaKenyaTherapeutiic EfficacyArtemether-lumefantrineDihydroartemisinin-piperaquine

Outcome Measures

Primary Outcomes (7)

  • Adequate clinical and parasitological response (ACPR) - AL

    Absence of parasitemia on day 28 for AL, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure.

    28 days

  • Adequate clinical and parasitological response (ACPR) - DP

    Absence of parasitemia on day 42 for DP, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure.

    42 days

  • Early treatment failure (ETF)

    Danger signs or severe malaria on day 1, 2 or 3, in the presence of parasitemia; * Parasitemia on day 2 higher than on day 0, irrespective of axillary temperature; * Parasitemia on day 3 with axillary temperature ≥ 37.5 °C; and * Parasitemia on day 3 ≥ 25% of count on day 0.

    3 days

  • Late clinical failure (LCF) - AL

    Danger signs or severe malaria in the presence of parasitemia on any day between day 4 and day 28 for AL in participants who did not previously meet any of the criteria of early treatment failure; and • Presence of parasitemia on any day between day 4 and day 28 for AL with axillary temperature ≥ 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure.

    28 days

  • Late clinical failure (LCF) - DP

    Danger signs or severe malaria in the presence of parasitemia on any day between day 4 and day 42 for DP in participants who did not previously meet any of the criteria of early treatment failure; and • Presence of parasitemia on any day between day 4 and day 42 for DP with axillary temperature ≥ 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure.

    42 days

  • Late parasitological failure (LPF) - AL

    Presence of parasitemia on any day between day 7 and day 28 for AL with axillary temperature \< 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure.

    28 days

  • Late parasitological failure (LPF) - DP

    Presence of parasitemia on any day between day 7 and day 42 for DP with axillary temperature \< 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure.

    42 days

Secondary Outcomes (5)

  • Change in hemoglobin over time

    42 days

  • ACPR by baseline parasite density

    42 days

  • Reinfection incidence rates and rate ratios by study arm, preventable fraction (AL)

    28 days

  • Reinfection incidence rates and rate ratios by study arm, preventable fraction (DP)

    42 days

  • Evaluate duration of malaria HRP2/pLDH RDT positivity after appropriate treatment with AL and DP

    42 days

Study Arms (2)

Artemether-lumefantrine (AL)

ACTIVE COMPARATOR

Participants will be randomized to receive a standard weight-based regimen of artemether-lumefantrine (Coartem®, Novartis Pharmaceuticals Corporation, Missouri, USA). Children in the AL arm received two daily doses (morning and evening) orally, over 3 days (6 doses total at 0, 8, 24, 36, 48, and 60 hours post initial dose, administered with food or milk at the clinic and at home). To promote and evaluate adherence, study staff called parents in the evening to remind them to give the AL dose to the child and to bring the blister pack to the clinic the next day for confirmation.

Drug: Artemether-lumefantrine (AL)

Dihydroartemisinin-piperaquine (DP)

ACTIVE COMPARATOR

Participants will be randomized to receive a standard weight-based regimen of dihydroartemisinin-piperaquine (DuoCotexin®; Holley-Cotec Pharmaceuticals, Beijing, China). DP was administered once a day for three days (at 0, 24, and 48 hours, orally).

Drug: Dihydroartemisinin-piperaquine (DP)

Interventions

Artemether-lumefantrine (AL)DRUG

AL is the current first-line antimalarial in Kenya, per Kenya Ministry of Health.

Also known as: Coartem
Artemether-lumefantrine (AL)
Dihydroartemisinin-piperaquine (DP)DRUG

DP is the current second-line antimalarial in Kenya, per Kenya Ministry of Health.

Also known as: Duocotexin
Dihydroartemisinin-piperaquine (DP)

Eligibility Criteria

Age6 Months - 59 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Age 6-59 months
  • Weight ≥ 5.0 kg
  • Axillary temperature ≥ 37.5C or history of fever in the past 24 hours
  • Hemoglobin ≥7 grams/deciliter at enrolment
  • Slide-confirmed mono-infection with Plasmodium falciparum and asexual parasite density between 2,000-200,000 parasites/μl
  • Live within the catchment boundaries of the study site (10km radius)
  • Able to swallow oral medication
  • Able and willing to comply with the protocol for the duration of the study
  • Able and willing to comply with the study visit schedule on days 2, 3, 7, 14, 21, 28, 35, and 42
  • Parent or caregiver has access to a phone and agrees to have study staff contact them for visit reminders during study period
  • Written informed consent provided by parent/guardian

You may not qualify if:

  • Presence of severe malaria or danger signs, including prostration, alteration in level of consciousness, respiratory distress, convulsions, or jaundice
  • Severe malnutrition according to WHO child growth standards (weight for age \<3 standard deviations)
  • Known hypersensitivity to AL or DP
  • Use of antimalarials or other drugs with antimalarial activity in the last 2 weeks
  • General clinical condition necessitates hospitalization
  • Evidence of concomitant infections at the time of presentation
  • Plan to travel or leave the area within the next 3 months
  • Previously enrolled in this study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Westercamp N, Owidhi M, Otieno K, Chebore W, Buff AM, Desai M, Kariuki S, Samuels AM. Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria among Children in Western Kenya, 2016 to 2017. Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0020722. doi: 10.1128/aac.00207-22. Epub 2022 Aug 29.

    PMID: 36036611DERIVED

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Simon Kariuki, PhD

    Kenya Medical Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Malaria Branch Chief

Study Record Dates

First Submitted

January 13, 2021

First Posted

September 29, 2021

Study Start

June 17, 2016

Primary Completion

March 13, 2017

Study Completion

December 31, 2020

Last Updated

September 29, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will share

Data will be available upon request

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
June 2021
Access Criteria
To be determined, depending on repository