Effectiveness of Artemisinin Combination Regimens in Falciparum Malaria

NCT00902811 | Unknown Phase 4

• 1 other identifier: YNG0901
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 4

Brief Summary

Antimalarial drug resistance is increasing nearly everywhere in the tropical world, confounding global attempts to "Roll Back Malaria." South East Asia has the most resistant malaria parasites in the world. This has limited the options for treatment in this region. Artemisinin-based combination therapy is now the recommended treatment for uncomplicated falciparum malaria. The success of this policy change in practice will depend on the efficacy of the components of the combination used, the population coverage achieved, high levels of adherence to treatment, low cost of the drugs, and preferably the drugs in a combination treatment should be formulated in a single tablet, to prevent one drug being taken without the partner drug. Until recently there were only two artemisinin-based fixed combinations available, artemether-lumefantrine and dihydroartemisinin-piperaquine; and only the former has international registration. More fixed combinations are needed urgently.

Conditions

Uncomplicated Falciparum Malaria

Keywords

uncomplicated falciparum malaria; artemisinin combination therapy

Outcome Measures

Primary Outcomes (1)

• Cure rate

  63 days

Secondary Outcomes (3)

• Early treatment failure

  Day 6

• Late treatment failure

  Day 63

• Adequate response

  Day 63

Study Arms (5)

AM(LT)

ACTIVE COMPARATOR

Artesunate (Arsumax®, Sanofi)

Drug: AM(LT)

AM(FDC)

EXPERIMENTAL

Artesunate-mefloquine fixed dose combination

Drug: AM(FDC)

AL

EXPERIMENTAL

artemether 20 mg - lumefantrine 120 mg co-formulated tabs

Drug: AL

DP

EXPERIMENTAL

40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/Piperaquine 160 mg tablets

Drug: DP

AA (FDC)

EXPERIMENTAL

Artesunate-amodiaquine fixed dose combination

Drug: AA(FDC)

Interventions

AM(FDC) DRUG

Artesunate-mefloquine fixed dose combination (artesunate 25mg/mefloquine hydrochloride 55mg, or artesunate 100mg/mefloquine hydrochloride 220mg), according to age-group.

Also known as: Far-Manguinhos, Brazil

AM(FDC)

AM(LT) DRUG

Artesunate (Arsumax®, Sanofi) 50 mg tabs given at 4 mg/Kg/day on day 0, day 1 and day 2 (total 12 mg/Kg) PLUS Mefloquine 250 mg base tabs given at 25 mg/Kg on day 0. Treatment is given in three equally divided daily doses to the nearest quarter tablet.

Also known as: Lariam®, Roche

AM(LT)

AL DRUG

Coartem®: artemether 20 mg - lumefantrine 120 mg co-formulated tabs (Coartem®, Novartis) given as six twice-daily doses over three days, according to weight-groups. The second dose should be taken 6 to 10 hours after the first dose, given at inclusion. Patients will be advised to take some fatty food (or encouraged to give breast feeding) before each dose is taken. Fatty food or milk will not be provided by the researchers.

Also known as: Coartem®

AL

DP DRUG

40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/ Piperaquine 160 mg tablets),. Treatment is given according to age groups. In the age group \<6yrs of age, a subdivision according to weight is made

Also known as: DuoCotecxin, Holley Pharm

DP

AA(FDC) DRUG

Artesunate-amodiaquine fixed dose combination (FDC) (Artesunate Amodiaquine Winthrop® Sanofi Aventis); Artesunate 25mg/amodiaquine 67.5mg; Artesunate 50mg/amodiaquine 135mg ; Artesunate 100mg/amodiaquine 270mg

Also known as: Artesunate Amodiaquine Winthrop® Sanofi Aventis

AA (FDC)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 6 months and
• Weight ≥ 5 kg, and
• Slide-confirmed infection with Plasmodium falciparum (including mixed infections), and
• Asexual parasite density between 500 and 200,000/µl of blood, and
• Informed consent from a parent or guardian aged at least 18 years.

You may not qualify if:

• General danger signs according to the WHO definition or
• Signs of severe/complicated malaria according to the WHO definition or
• Severe anaemia (haemoglobin \< 5 g/dL), or
• Known history of hypersensitivity to any of the study drugs, or
• Severe malnutrition (as defined by a weight-for-height below 70% of median and/or symmetrical oedemas involving at least the feet), or
• History of psychiatric diseases, or
• Having received a full course treatment including MQ in the preceding 9 weeks or
• Having received any other antimalarials in the previous 48 hours.

Sponsors & Collaborators

• Medecins Sans Frontieres, Netherlands: lead
• Mahidol University: collaborator
• University of Oxford: collaborator
• Disease Control, Department of Health, Myanmar: collaborator

Study Sites (4)

Dabhine and Mingan Clinic

Sittwe, Rakhine State, Burma

RECRUITING

Myit Kyi Nar Clinic

Kachin, Burma

RECRUITING

Myothugyi Rural Health Center, Bu Thee Daung

Maungdaw, Burma

RECRUITING

Lashio Clinic

Shan, Burma

RECRUITING

Related Publications (1)

• Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo AP, Naing AL, Nyo MY, Myint NZ, Imwong M, Ashley E, Lee SJ, White NJ. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis. 2010 Oct;10(10):673-81. doi: 10.1016/S1473-3099(10)70187-0. Epub 2010 Sep 9.

  PMID: 20832366 DERIVED

MeSH Terms

Interventions

Mefloquine; Artemether, Lumefantrine Drug Combination

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Frank Smithuis, MD

  Medecins Sans Frontieres, Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frank Smithuis, MD

CONTACT

frank_smithuis@yahoo.com

Phaikyeong Cheah, PhD

CONTACT

phaikyeong@tropmedres.ac

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 15, 2009
• Study Start: December 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 15, 2009

Record last verified: 2009-05

Locations

BU (4)