Autor/a:
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Varo, Rosauro; Crowley, Valerie M.; Sitoe, Antonio; Madrid, Lola; Serghides, Lena; Bila, Rubao; Mucavele, Helio; Mayor Aparicio, Alfredo Gabriel; Bassat Orellana, Quique; Kain, Kevin C.
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Abstract:
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BACKGROUND: Despite the widespread use and availability of
rapidly acting anti-malarials, the fatality rate of severe
malaria in sub-Saharan Africa remains high. Adjunctive therapies
that target the host response to malaria infection may further
decrease mortality over that of anti-malarial agents alone.
Peroxisome proliferator-activated receptor-gamma agonists (e.g.
rosiglitazone) have been shown to act on several pathways
implicated in the pathogenesis of severe malaria and may improve
clinical outcome as an adjunctive intervention. METHODS: In this
study, the safety and tolerability of adjunctive rosiglitazone
in paediatric uncomplicated malaria infection was evaluated in
Mozambique, as a prelude to its evaluation in a randomized
controlled trial in paediatric severe malaria. The study was a
prospective, randomized, double-blind, placebo-controlled, phase
IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4
days versus placebo as adjunctive treatment in addition to
Mozambican standard of care (artemisinin combination therapy
Coartem(R)) in children with uncomplicated malaria. The primary
outcomes were tolerability and safety, including clinical,
haematological, biochemical, and electrocardiographic
evaluations. RESULTS: Thirty children were enrolled: 20 were
assigned to rosiglitazone and 10 to placebo. Rosiglitazone
treatment did not induce hypoglycaemia nor significantly alter
clinical, biochemical, haematological, or electrocardiographic
parameters. CONCLUSIONS: Adjunctive rosiglitazone was safe and
well-tolerated in children with uncomplicated malaria,
permitting the extension of its evaluation as adjunctive therapy
for severe malaria. The trial is registered with
Clinicaltrials.gov, NCT02694874. |