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Effectiveness of Artemisinin Combination Regimens in Falciparum Malaria (ACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00902811
Recruitment Status : Unknown
Verified May 2009 by Medecins Sans Frontieres, Netherlands.
Recruitment status was:  Recruiting
First Posted : May 15, 2009
Last Update Posted : May 15, 2009
Mahidol University
University of Oxford
Disease Control, Department of Health, Myanmar
Information provided by:
Medecins Sans Frontieres, Netherlands

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.

Condition or disease Intervention/treatment Phase
Uncomplicated Falciparum Malaria Drug: AM(FDC) Drug: AM(LT) Drug: AL Drug: DP Drug: AA(FDC) Phase 4

Detailed Description:

Malaria in Myanmar:

In Myanmar, malaria is the number one cause of morbidity. According to the Department of Health (DoH) and WHO there are approximately 500,000 patients with malaria each year. About 80% of reported infections are due to Plasmodium falciparum and 20% are due to Plasmodium vivax. This is likely to be a severe underestimation. MSF-Holland alone treats already 250,000 slide positive malaria patients per year in an area of mixed endemicity covering a population of less that 1 million patients out of a total population of 54 million in the country.

Chloroquine was the first line treatment for falciparum malaria for the last five decades. In 1996 and 1998 MSF-Holland with support from the Wellcome Trust (Prof N. White) performed studies in the northern and western part of the country, in which very high in-vivo resistance levels to chloroquine and sulfadoxine-pyrimethamine were demonstrated1,2. Combination treatment of mefloquine plus artesunate (loose tablets) [MA(LT)]and treatment with dihydroartemisinin-piperaquine (DP) both proved highly efficacious (99-100%)3,4. The studies performed by MSF provided an important component of the evidence used to convince the health authorities that a change of national protocol was needed. In 2001, the DOH of Myanmar changed the national protocol for the treatment of uncomplicated falciparum malaria; a 3 day treatment of mefloquine-artesunate was chosen to become the first line treatment. Artemether-lumefantrine (AL) and DP are also mentioned in the national protocol as effective treatment regimens, but there is a call in the protocol for more research of these treatments.

These changes in policy are a very good step forward and were widely respected. In practice, some problems remain.

MSF has implemented large malaria activities in Myanmar over the past decade. The programme has performed a diagnostic test for malaria for approximately 3,000,000 patients and approximately 1,500,000 patients have been treated with artemisinin combination treatment (ACT).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparing the Effectiveness of 5 Artemisinin Combination Treatment Regimens in the Treatment of Uncomplicated Falciparum Malaria
Study Start Date : December 2008
Estimated Primary Completion Date : October 2009
Estimated Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: AM(LT)
Artesunate (Arsumax®, Sanofi)
Drug: AM(LT)
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.
Other Name: Lariam®, Roche

Experimental: AM(FDC)
Artesunate-mefloquine fixed dose combination
Drug: AM(FDC)
Artesunate-mefloquine fixed dose combination (artesunate 25mg/mefloquine hydrochloride 55mg, or artesunate 100mg/mefloquine hydrochloride 220mg), according to age-group.
Other Name: Far-Manguinhos, Brazil

Experimental: AL
artemether 20 mg - lumefantrine 120 mg co-formulated tabs
Drug: AL
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.
Other Name: Coartem®

Experimental: DP
40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/Piperaquine 160 mg tablets
Drug: DP
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
Other Name: DuoCotecxin, Holley Pharm

Experimental: AA (FDC)
Artesunate-amodiaquine fixed dose combination
Drug: AA(FDC)
Artesunate-amodiaquine fixed dose combination (FDC) (Artesunate Amodiaquine Winthrop® Sanofi Aventis); Artesunate 25mg/amodiaquine 67.5mg; Artesunate 50mg/amodiaquine 135mg ; Artesunate 100mg/amodiaquine 270mg
Other Name: Artesunate Amodiaquine Winthrop® Sanofi Aventis

Primary Outcome Measures :
  1. Cure rate [ Time Frame: 63 days ]

Secondary Outcome Measures :
  1. Early treatment failure [ Time Frame: Day 6 ]
  2. Late treatment failure [ Time Frame: Day 63 ]
  3. Adequate response [ Time Frame: Day 63 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria

  • 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.

Exclusion criteria

  • 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
  • Concomitant febrile illness due to causes other than malaria with the potential to confound study outcome (measles, acute lower tract respiratory infection, otitis media, tonsillitis, abscesses, severe diarrhoea with dehydration, etc.; mild flu should not lead to exclusion) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00902811

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Contact: Frank Smithuis, MD
Contact: Phaikyeong Cheah, PhD

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Dabhine and Mingan Clinic Recruiting
Sittwe, Rakhine, Myanmar
Contact: Pyay Phyo Aung   
Principal Investigator: Pyay Phyo Aung, MD         
Myit Kyi Nar Clinic Recruiting
Kachin, Myanmar
Contact: Mya Nee Nyo   
Principal Investigator: Mya Nee Nyo, MD         
Myothugyi Rural Health Center, Bu Thee Daung Recruiting
Maungdaw, Myanmar
Contact: Arkar Linn Naing   
Principal Investigator: Arkar Linn Naing, MD         
Lashio Clinic Recruiting
Shan, Myanmar
Contact: Naing Nyo, MD         
Principal Investigator: Naing Zaw, MD         
Sponsors and Collaborators
Medecins Sans Frontieres, Netherlands
Mahidol University
University of Oxford
Disease Control, Department of Health, Myanmar
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Principal Investigator: Frank Smithuis, MD Medecins Sans Frontieres, Netherlands

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Frank Smithuis, Medecins Sans Frontieres, Holland Identifier: NCT00902811     History of Changes
Other Study ID Numbers: YNG0901
First Posted: May 15, 2009    Key Record Dates
Last Update Posted: May 15, 2009
Last Verified: May 2009
Keywords provided by Medecins Sans Frontieres, Netherlands:
uncomplicated falciparum malaria
artemisinin combination therapy
Additional relevant MeSH terms:
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Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artemether, Lumefantrine Drug Combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Antiplatyhelmintic Agents