NCT00868465

Brief Summary

Artemisinin combination therapy (ACT) with artemether lumefantrine (AL) is currently the first line treatment policy in Tanzania. AL is an efficacious drug that also has the capacity to reduce malaria transmission to mosquitoes. Nevertheless, there is concern about the development of parasite resistance against AL and there have been very few clinical trials that compared different ACT regimens. A recent clinical trial shows that the combination of dihydroartemisinin-piperaquine (DP) may be more efficacious than AL and may have a more pronounced beneficial effect on post-treatment malaria transmission. Screening for molecular markers that are related to parasite susceptibility to ACT drugs and to post-ACT treatment malaria transmission can assist in preventing the development and spread of ACT resistance. In the current study, the investigators compared AL and DP for the treatment of uncomplicated malaria. The investigators endpoints are

  • clinical efficacy
  • post-treatment gametocytaemia by molecular techniques
  • post-treatment malaria transmission.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
600

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2009

Geographic Reach
2 countries

2 active sites

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

March 24, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 25, 2009

Completed
7 days until next milestone

Study Start

First participant enrolled

April 1, 2009

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2010

Completed
Last Updated

June 7, 2010

Status Verified

April 1, 2009

Enrollment Period

1.1 years

First QC Date

March 24, 2009

Last Update Submit

June 4, 2010

Conditions

Uncomplicated Malaria

Outcome Measures

Primary Outcomes (1)

  • To determine the clinical efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in the treatment of uncomplicated falciparum malaria in children living in north-western Tanzania and in western Kenya.

    during 42 day follow-up

Secondary Outcomes (7)

  • To determine (sub-microscopic) gametocyte carriage after treatment with AL and DP

    during 42 day follow-up

  • To determine malaria transmission to mosquitoes after treatment with AL or DP

    day 7 after initiation treatment

  • To determine molecular markers that are predictive of reduced susceptibility of parasite strains for AL and DP

    day 7 after initiation treatment

  • To determine molecular markers that are related to gametocytaemia or malaria transmission after treatment with AL and DP

    during 42 day follow-up

  • To determine the relation between treatment success and the presence of anti-malaria antibodies

    during 42 day follow-up

  • +2 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

Artemether-lumefantrine; currently the first line treatment in Tanzania

Drug: Artemether-Lumefantrine

2

EXPERIMENTAL

Dihydroartemisinin-piperaquine, alternative ACT

Drug: Dihydroartemisinin-piperaquine

Interventions

Artemether-LumefantrineDRUG

Treatment with artemether-lumefantrine (AL; Coartem; Novartis Pharma), administered as half a tablet (20 mg of artemether and 120 mg of lumefantrine) per 5 kg of body weight in a 6-dose regimen (at enrolment and 8, 20, 32, 44, and 56 h \[+/-90 min\] after the initiation of treatment). AL is currently the first line treatment in Tanzania

Also known as: Coartem; Riamet
1
Dihydroartemisinin-piperaquineDRUG

Dihydroartemisinin-piperaquine (DP; Artekin; Duocotexin, Holley Pharm, 40 mg dihydroartemisinin/320 mg piperaquine tablets), with a dihydroartemisinin dose of 2.5 mg per kilogram and a piperaquine phosphate dose of 20 mg per kilogram daily for 3 days. DH is registered in Tanzania as Artekin and has been tested extensively in Asia and recently in clinical trials in Uganda and Rwanda

Also known as: Artekin
2

Eligibility Criteria

Age6 Months - 10 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Age 6 months - 10 years
  • Residents of research area (5 km around the clinic)
  • Willingness to come for complete scheduled follow-up.
  • Uncomplicated malaria with P. falciparum mono-infection
  • Parasitaemia of 1000-200,000 parasites/ul
  • Temperature \> 37.5°C and \< 39.5°C, or history of fever in previous 24 hours.
  • No history of adverse reactions to AL
  • Understanding of the procedures of the study by parent or guardian and willing to participate by signing informed consent forms.

You may not qualify if:

  • General signs of severe malaria
  • Haemoglobin concentration \< 5g/dl
  • Presence of disease other than malaria causing febrile conditions
  • Mixed infection with P. malariae or other non-falciparum malaria species
  • Unwilling to participate and sign informed consent forms.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

International Centre for Insect Physiology and Ecology - St. Judes Clinic

Mbita, Suba District, Kenya

Location

Kilimanjaro Christian Medical Centre, Magugu Field Site

Moshi, Kilimanjaro, Tanzania

Location

Related Publications (4)

  • Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, Githure JI, Ord R, Sutherland CJ, Omar SA, Sauerwein RW. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis. 2006 Apr 15;193(8):1151-9. doi: 10.1086/503051. Epub 2006 Mar 15.

    PMID: 16544256BACKGROUND

  • Hallett RL, Sutherland CJ, Alexander N, Ord R, Jawara M, Drakeley CJ, Pinder M, Walraven G, Targett GA, Alloueche A. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes. Antimicrob Agents Chemother. 2004 Oct;48(10):3940-3. doi: 10.1128/AAC.48.10.3940-3943.2004.

    PMID: 15388456BACKGROUND

  • Muwanguzi J, Henriques G, Sawa P, Bousema T, Sutherland CJ, Beshir KB. Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children. Malar J. 2016 Jan 22;15:36. doi: 10.1186/s12936-016-1095-y.

    PMID: 26801909DERIVED

  • Sawa P, Shekalaghe SA, Drakeley CJ, Sutherland CJ, Mweresa CK, Baidjoe AY, Manjurano A, Kavishe RA, Beshir KB, Yussuf RU, Omar SA, Hermsen CC, Okell L, Schallig HD, Sauerwein RW, Hallett RL, Bousema T. Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial. J Infect Dis. 2013 Jun 1;207(11):1637-45. doi: 10.1093/infdis/jit077. Epub 2013 Mar 6.

    PMID: 23468056DERIVED

MeSH Terms

Interventions

Artemether, Lumefantrine Drug Combination

Intervention Hierarchy (Ancestors)

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

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 24, 2009

First Posted

March 25, 2009

Study Start

April 1, 2009

Primary Completion

May 1, 2010

Study Completion

May 1, 2010

Last Updated

June 7, 2010

Record last verified: 2009-04

Locations

KE(1)TA(1)