Malaria Clinical Trial
Official title:
A Non-Inferiority, Open-Labelled, Randomised Trial Of The Efficacy And Safety Of Artesunate-Amodiaquine, Artemether-Lumefantrine, And Artesunate-Lapdap For Treatment Of Uncomplicated P. Falciparum Malaria Among Children In Ghana
Case management is one of the key strategies for malaria control in most endemic countries.
Plasmodium falciparum malaria is becoming resistant to commonly used and cheap antimalarial
drugs such as chloroquine, amodiaquine, and sulfadoxine-pyrimethamine (SP). Thus the safety
and efficacy of new anti-malarial drugs need to be tested in sites with well-characterised
malariometric indices in order to make appropriate treatment policies.
Artemisinin-based combination chemotherapies have been documented to consistently produce
faster relief of clinical symptoms and parasite clearance in uncomplicated falciparum
malaria than any other currently used antimalarial drugs. So far, artesunate-amodiaquine
(AS-AQ) and artemether-lumefantrine (AR-LM) are the only two registered fixed-dose
artemisinin combination chemotherapies produced at industrial scale, with good manufacturing
practices and already used in Africa. Several African countries, including Ghana, are
therefore introducing either AS-AQ or AR-LM as first-line antimalarials or evaluating the
case for such a change. Clearly, a direct comparison of both the safety and efficacy
profiles of the two combinations under different epidemiological conditions is urgently
needed to guide informed decisions on the most appropriate antimalarial first-line treatment
regimen.
This study aims to evaluate the efficacy and safety of artesunate-amodiaquine combination
therapy, artemether-lumefantrine, and artesunate-lapdap in an open-labelled, randomised,
non-inferiority drug trial.
The study results will inform future decisions on first- and second-line treatments for
uncomplicated P. falciparum malaria with respect to efficacy and safety in Ghana.
A study funded by the GMP-LSHTM in the Kintampo district of Ghana is currently assessing the
efficacy of SP as part of a comprehensive process of characterising the site into the
patterns of seasonal dynamics of P. falciparum transmission, infection, and morbidity. The
initial results from this study have demonstrated a high parasitological failure rate(18%)
on day 14 of treatment, an indication that SP is no longer suitable for use in Ghana.
Artesunate combination therapies (ACTs) have been found to be efficacious and safe,
producing rapid clearance of parasites and malaria symptoms; they are very well tolerated.
Lapdap is a newly registered, relatively cheap antimalarial with short half-life and has
been found to be highly efficacious in strict trial conditions for treatment of acute
uncomplicated falciparum infections in endemic sites in Africa. Despite the rapid clearance
of lapdap, children treated with this drug did not have higher incidence of malaria episodes
than those treated with SP though haematological adverse effects have been documented to be
more common with lapdap than with SP. At present, the fixed-dose combination regimens of
artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AR-LM) are the only two
registered artemisinin combination chemotherapies produced at industrial scale, with good
manufacturing practices and already used in Africa. Several African countries are
introducing either AS-AQ or AR-LM as first-line antimalarials or evaluating the case for
such a change. Ghana, has just changed its antimalarial drug policy to
artesunate-amodiaquine combination therapy (AS-AQ) as first line drug. The selection of this
new ACT has been driven partly by cost of treatment, but a critical look at the safety and
efficacy of ACTs in Ghana has yet to be done.
This study aims to evaluate the efficacy and safety of artesunate-amodiaquine combination
therapy (AS-AQ), Artemether-lumefantrine (Coartem), and Artesunate-lapdap) in a drug
non-inferiority study.
Objectives
Primary objective:
• To evaluate the efficacy of artesunate-amodiaquine versus artemether-lumefantrine, versus
artesunate-lapdap in the treatment of children aged 6 months to ten years, infected with
uncomplicated falciparum malaria, at the paediatric outpatient clinic in the Kintampo
hospital.
Secondary objectives:
• To evaluate the safety of artesunate-amodiaquine versus artemether-lumefantrine, versus
artesunate-lapdap in the treatment of children 6 months to ten years with uncomplicated
falciparum malaria.
Study design and methods
Study site: This study is being conducted in Kintampo district in the middle belt of Ghana
where the investigators in the Kintampo Health Research Centre are located. Kintampo Health
Research Centre (KHRC), one of three research centres under the Health Research Unit (HRU)
of the Ghana Health Service, Ghana, lies within the forest-savannah, transitional ecological
zone in the Brong Ahafo Region of Ghana.
Study design:
This is a randomised, open-labelled, non-inferiority drug trial. At the Kintampo district
hospital, 510 paediatric outpatients (refer sample size calculation) with uncomplicated P.
falciparum malaria and aged between 6 months and 10 years will be recruited and randomly
assigned to one of the three study arms: (i) Artesunate-Amodiaquine (AS-AQ), (ii)
Artemether-Lumefantrine (AR-LM), or (iii) Artesunate-lapdap (AS-LP). The classification of
clinical and parasitological responses will follow the relevant WHO protocol for areas of
intense transmission. Follow-up, however, will be extended beyond day 14 up to day 28 to
increase the sensitivity of the in vivo test. PCR-based genotyping comparing pairs of
parasite isolates from day 0 and day of asexual parasite reappearance will be used to
distinguish between recrudescence and re-infection.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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