Efficacy of Artemether-lumefantrine, Artesunate-amodiaquine and Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Malawi

Summary

Background: Malaria is a cause of substantial morbidity and mortality in Malawi. Prompt and effective treatment of uncomplicated malaria remains a key strategy to reduce the public health burden of malaria. Due to the rising resistance to and falling efficacy of sulfadoxine-pyrimethamine, the first-line treatment of uncomplicated malaria from 1993 to 2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines in 2007. The revised treatment guidelines recommend artemether-lumefantrine as the first-line treatment for uncomplicated malaria and artesunate-amodiaquine as a second-line treatment for uncomplicated malaria. The change in policy was based primarily on efficacy data from other countries in sub-Saharan Africa. However, although both artemether-lumefantrine and artesunate-amodiaquine have been in use in Malawi since 2007, there are relatively few studies assessing their efficacy. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine was found to be efficacious.1 In addition, a more recent assessment of artemether-lumefantrine in vivo efficacy conducted in six sites in Malawi in 2009 also suggests that the standard formulation artemether-lumefantrine remains highly efficacious (Kamija Phiri, personal communication).

Although, some Malawi-specific data on the in vivo efficacy of the standard formulation of artemether-lumefantrine exists, there are additional data that is needed to support the current policy and inform future policy decisions. In 2010 the NMCP has introduced the dispersible formulation of artemether-lumefantrine (Coartem-D™) for use as a first-line antimalarial in Malawi, due to the global unavailability of the standard formulation of artemether-lumefantrine from Novartis, the key supplier of the standard formulation of artemether-lumefantrine (Coartem™) in Malawi. In light of these developments, an assessment of the efficacy, safety and tolerability of the dispersible formulation of artemether-lumefantrine is warranted. In addition, the efficacy, safety and tolerability of co-formulated artesunate-amodiaquine, the current secondline treatment for uncomplicated malaria, has never been assessed in Malawi and should be evaluated. Lastly, dihydroartemisinin-piperaquine has recently been added to the new World Health Organization (WHO) guidelines for the treatment of uncomplicated malaria. This promising new antimalarial might have a role as a first-line or second-line antimalarial for the treatment of uncomplicated malaria, but there are no efficacy and safety data from Malawi. This knowledge gap needs to be addressed to help inform policy makers about the potential role of dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in Malawi.

Objective: Efficacy and safety of the dispersible formulation of artemether-lumefantrine, co-formulated artesunate-amodiaquine and co-formulated dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga District Hospital- Malawi

Methods: An antimalarial drug efficacy trial will be conducted in Malawi. The participants will be febrile people 6-59 months old with confirmed uncomplicated P. falciparum infection. Patients will be sequentially allocated to receive treatment with either the dispersible formulation of artemether-lumefantrine at a dose of 2/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days; or co-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days; or co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug effi¬cacy. The study will be conducted from January to December, 2011. The results of this study will be used to assist the Ministry of Health in Malawi in assessing the current national treatment guidelines for uncomplicated P. falciparum malaria.

Conditions

• Malaria, Falciparum

Interventions

DRUG

Artemether-lumefantrine combination

Dispersible formulation of artemether-lumefantrine at a dose of 2/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days

DRUG

Artesunate-amodiaquine combination

Co-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days

DRUG

Dihydroartemisinin-piperaquine

Co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days

Sponsors & Collaborators

• Kamuzu University of Health Sciences

  collaborator OTHER

• Centers for Disease Control and Prevention

  lead FED

Principal Investigators

• Jacek Skarbinski, MD · Centers for Disease Control and Prevention

• Don Mathanga, MBBS PhD · Kamuzu University of Health Sciences

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

59 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-08-31

Primary Completion

2012-06-30

Completion

2012-06-30

Countries

• Malawi

Study Locations