Effectiveness of Artemisinin Combination Regimens in Falciparum Malaria

Phase 4

• Conditions: Uncomplicated Falciparum Malaria
• Interventions: Drug: AM(LT); Drug: AM(FDC); Drug: DP; Drug: AA(FDC); Drug: AL

• Registration Number: NCT00902811
• Lead Sponsor: 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.

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).

Study Timeline

• Study Start: 2008-12
• Study First Submitted: 2009-04-30
• Status Verified: 2009-05
• Study First Submitted QC: 2009-05-14
• Last Update Submitted: 2009-05-14
• Study First Posted: 2009-05-15
• Last Update Posted: 2009-05-15
• Primary Completion: 2009-10
• Study Completion: 2009-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AM(LT)	AM(LT)	Artesunate (Arsumax®, Sanofi)
AM(FDC)	AM(FDC)	Artesunate-mefloquine fixed dose combination
DP	DP	40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/Piperaquine 160 mg tablets
AA (FDC)	AA(FDC)	Artesunate-amodiaquine fixed dose combination
AL	AL	artemether 20 mg - lumefantrine 120 mg co-formulated tabs

Primary Outcome Measures

Name	Time	Method
Cure rate	63 days

Secondary Outcome Measures

Name	Time	Method
Early treatment failure	Day 6
Late treatment failure	Day 63
Adequate response	Day 63

Trial Locations

Locations (4)

Dabhine and Mingan Clinic; 🇲🇲 Sittwe, Rakhine, Myanmar

Myit Kyi Nar Clinic; 🇲🇲 Kachin, Myanmar

Myothugyi Rural Health Center, Bu Thee Daung; 🇲🇲 Maungdaw, Myanmar

Lashio Clinic; 🇲🇲 Shan, Myanmar