NCT03764527

Brief Summary

The primary objective of the study was to determine PCR corrected cure-rates up to day 42 in children with uncomplicated malaria, treated with either Artesunate + Amodiaquine or Coartem®. Secondary objectives were to determine safety and possible selection of mutations related to the resistance of the tested drugs.

Trial Health

100
On Track

Trial Health Score

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

Enrollment
408

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2002

Shorter than P25 for phase_4

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

November 1, 2002

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 17, 2003

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 17, 2003

Completed
15.8 years until next milestone

First Submitted

Initial submission to the registry

December 3, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 5, 2018

Completed
Last Updated

December 6, 2018

Status Verified

December 1, 2018

Enrollment Period

4 months

First QC Date

December 3, 2018

Last Update Submit

December 5, 2018

Conditions

Plasmodium Falciparum Malaria

Keywords

Artemether-LumefantrineCoartemArtesunateAmodiaquineZanzibar

Outcome Measures

Primary Outcomes (1)

  • PCR corrected cure-rates up to day 42 in children with uncomplicated malaria, treated with either Artesunate + Amodiaquine (AA) or Coartem® (CO)

    Comparing PCR adjusted parasitological cure rate (PCR-APCR) between the two treatment options up to day 42. Parasitological cure will be adjusted using PCR genotyping of msp2 marker. Recrudescence is defined as the presence of at least one matching allelic band, and reinfection as the absence of any matching allelic band on day 0 and day of recurring parasitaemia. Patients with recurrent parasitaemia having missing filter paper sample or negative PCR results will be considered uncertain with regards to PCR adjusted outcome.

    42 days

Secondary Outcomes (6)

  • Safety of treatment with Artesunate + Amodiaquine (AA) or Coartem® (CO): Proportion of subjects with adverse events

    42 days

  • Parasite clearance

    42 days

  • Gametocyte carriage

    42 days

  • Fever clearance

    42 days

  • Hemoglobin

    42 days

  • +1 more secondary outcomes

Study Arms (2)

Artemether-lumefantrine (AL)

ACTIVE COMPARATOR

One tablet of artemether-lumefantrine (Coartem®) was administered twice daily for 3 days to children with a body weight of 9 to \<15 kg, and 2 tablets were administered twice daily for 3 days to children with a body weight of \>15 to 25 kg. All doses were taken under direct observation.

Drug: Artemether-lumefantrine

Artesunate + Amodiaquine (AA)

ACTIVE COMPARATOR

Artesunate + amodiaquine (ASAQ) was administered as follows: 4 mg/kg body weight of artesunate plus 10 mg/kg body weight of amodiaquine once daily for 3 days under direct observation.

Drug: Coadministered Artesunate plus Amodiaquine

Interventions

Artemether-lumefantrineDRUG

Two doses a day for 3 days, under supervision

Also known as: Coartem®
Artemether-lumefantrine (AL)
Coadministered Artesunate plus AmodiaquineDRUG

One dose a day for 3 days, under supervision

Artesunate + Amodiaquine (AA)

Eligibility Criteria

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

You may qualify if:

  • Children age 6-59 months and body weight ≥6 kg (AQ+AS); 9-59 months and body weight ≥9 kg (AL)
  • Fever or history of fever in the preceding 24 hours
  • Parasitemia ≥2000 ≤200.000 parasites per µl
  • Informed consent given by the child's parent or other adult guardian

You may not qualify if:

  • Signs of severe malaria or other danger signs, such as: 1.Unconsciousness; 2. Not able to sit or stand; 3.Severe anaemia (Hb ≤ 5 g/dl); 4.Convulsions; 5. Shock (systolic BP\<50 mmHg); 6. Not able to drink or breastfeed; 7. Vomiting 3 times or more the past 24 hrs
  • Other diseases associated with fever
  • History of allergy to test drugs
  • History of intake of any drugs other than paracetamol and aspirin within 3 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (3)

  • Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005 Oct 15;41(8):1079-86. doi: 10.1086/444460. Epub 2005 Sep 13.

    PMID: 16163624RESULT

  • Sisowath C, Ferreira PE, Bustamante LY, Dahlstrom S, Martensson A, Bjorkman A, Krishna S, Gil JP. The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa. Trop Med Int Health. 2007 Jun;12(6):736-42. doi: 10.1111/j.1365-3156.2007.01843.x.

    PMID: 17550470RESULT

  • Holmgren G, Hamrin J, Svard J, Martensson A, Gil JP, Bjorkman A. Selection of pfmdr1 mutations after amodiaquine monotherapy and amodiaquine plus artemisinin combination therapy in East Africa. Infect Genet Evol. 2007 Sep;7(5):562-9. doi: 10.1016/j.meegid.2007.03.005. Epub 2007 Mar 31.

    PMID: 17467344RESULT

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug CombinationAmodiaquine

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 PreparationsAminoquinolinesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Abdullah Ali

    Zanzibar Malaria Control Programme

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Masking Details
The AQ+AS (AA) group received their drugs under direct observation once daily for 3 days. The Coartem (CO) group received their drugs twice daily, the second (evening) dose also under supervision. Drug treatment was thus not be blinded.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: A comparative randomised study comparing oral treatment with AQ + AS and CO of uncomplicated falciparum malaria in children.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

December 3, 2018

First Posted

December 5, 2018

Study Start

November 1, 2002

Primary Completion

February 17, 2003

Study Completion

February 17, 2003

Last Updated

December 6, 2018

Record last verified: 2018-12