Efficacy of Artemether-lumefantrine, Artesunate-amodiaquine and Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Malawi
Information source: Centers for Disease Control and Prevention
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria, Falciparum
Intervention: Artemether-lumefantrine combination (Drug); Artesunate-amodiaquine combination (Drug); Dihydroartemisinin-piperaquine (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Centers for Disease Control and Prevention Official(s) and/or principal investigator(s):
Jacek Skarbinski, MD, Principal Investigator, Affiliation: Centers for Disease Control and Prevention
Don Mathanga, MBBS PhD, Principal Investigator, Affiliation: University of Malawi College of Medicine
Overall contact:
Don Mathanga, MBBS PhD, Phone: +265 1 870 145, Email: dmathang@mac.medcol.mw
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.
Clinical Details
Official title: 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 in Machinga District, Malawi
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Adequate clinical and parasitological response (ACPR)
Eligibility
Minimum age: 6 Months.
Maximum age: 59 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- age between 6 to 59 months;
- mono-infection with P. falciparum detected by microscopy;
- parasitaemia of 2,000-200,000/µl asexual forms;
- presence of axillary or tympanic temperature ≥ 37. 5 °C or oral or rectal temperature
of ≥ 38 °C or history of fever during the past 24 h;
- ability to swallow oral medication;
- ability and willingness to comply with the study protocol for the duration of the
study and to comply with the study visit schedule; and
- informed consent from the parent or guardian of the child.
Exclusion Criteria:
- presence of general danger signs in children aged under 5 years or signs of severe
falciparum malaria according to the definitions of WHO (Appendix 1);
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe malnutrition (defined as a child whose growth stand¬ard is below - 3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm
circumference < 110 mm) and calculated using EpiInfo 2002 EpiNut calculator;
- presence of febrile conditions due to diseases other than malaria (e. g. measles,
acute lower respiratory tract infection, severe diarrhoea with dehydration) or other
known underlying chronic or severe diseases (e. g. cardiac, renal and hepatic
diseases, HIV/AIDS);
- regular medication, which may interfere with antimalarial pharmacokinetics;
- history of hypersensitivity reactions or contraindications to any of the medicine(s)
being tested or used as alternative treatment(s).
Locations and Contacts
Don Mathanga, MBBS PhD, Phone: +265 1 870 145, Email: dmathang@mac.medcol.mw
Machinga District Hospital, Liwonde, Malawi; Recruiting
Don Mathanga, MBBS PhD, Phone: +265 1 870 145
Don Mathanga, MBBS PhD, Principal Investigator
Additional Information
Starting date: August 2011
Last updated: November 11, 2011
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