E.W. "Al" Thrasher
Status: Funded - Open
A randomized, placebo-controlled trial of magnesium sulphate for severe HFMD in Vietnamese children
Bridget Wills, BMBS, DM, FRCPCH
BACKGROUND: Hand foot and mouth disease (HFMD) is a common infectious disease caused by a variety of enteroviruses. A small proportion of those infected with enterovirus 71 develop neurological and systemic complications that may prove fatal.
GAP: In children with severe HFMD the particular part of the brain that regulates heart rate, blood pressure, and breathing responses can be affected. Management of this complication is very difficult; we currently use an expensive drug that is hard to obtain and has significant side effects, without having good evidence that it is effective. Magnesium sulphate (Mg) is a cheap, readily available drug that has been used in other diseases with similar complications, and there is preliminary data that suggests it may be effective for HFMD with brain involvement.
HYPOTHESIS: We hypothesize that early intervention with Mg, when brain involvement first becomes apparent, will control cardiovascular instability and prevent progression to severe disease.
METHODS: We will perform a randomized blinded trial comparing intravenous Mg with placebo, in children with clinical signs of HFMD plus hypertension exceeding a pre-specified age-related threshold together with at least one other sign of brain involvement. Patients will receive an initial loading dose followed by a maintenance infusion, of either Mg or identical placebo, for 72 hours. The primary endpoint is a composite indicating disease progression, including one or more of the following:
– Specific blood pressure criteria necessitating addition of the current standard therapy
– Need for mechanical ventilation
– Development of shock
Safety endpoints will include the number of adverse events and severe adverse events that occur in the two treatment arms. A number of secondary endpoints will also be assessed, in particular the presence of neurological sequelae at discharge in survivors, as well as neurodevelopmental status 6 months after discharge.
IMPACT: Given the very large numbers of HFMD cases currently being seen in hospitals in Asia, if Mg is shown to be effective in controlling brain involvement and preventing severe HFMD complications this would be of major importance for paediatric care throughout the Asian region.