Magnesium Sulphate for Severe Hand, Foot and Mouth Disease in Vietnam
Status:
Completed
Trial end date:
2016-12-28
Target enrollment:
Participant gender:
Summary
Hand foot and mouth disease (HFMD) is a common infectious disease caused by a number of
different viruses - a small proportion of children infected with a particular type of
enterovirus (EV71) develop neurological and systemic complications that may prove fatal. Very
large epidemics of EV71 related HFMD have occurred across Asia in recent years; in 2011, in
excess of 100,000 Vietnamese children were diagnosed with HFMD and 164 died.
In children with severe HFMD the particular part of the brain that regulates the heart, blood
circulation, and breathing responses can be affected. Management of this complication is very
difficult and we currently use an expensive drug (milrinone) 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 we have preliminary data from a small case series
that suggests it might be a good treatment for HFMD patients with signs indicating this type
of brain involvement.
We think that early intervention with Mg, when signs of brain involvement are still
relatively mild, will control this problem better than waiting until it is well established
and giving milrinone as at present, and this in turn may prevent progression to severe
disease. The aims of the project are to evaluate the effects of Mg on hypertension, signs of
brain dysfunction, outcome (death or neurological sequelae), changes in a variety of blood
and urine components, and measures of cardiovascular function, in severe HFMD.
The study design is a randomized double-blind placebo-controlled clinical trial. Children on
the pediatric intensive care unit with a clinical diagnosis of hand, foot and mouth disease
will be eligible for enrolment if the blood pressure exceeds the internationally recognized
threshold for Stage 1 hypertension, they exhibit at least one other sign of brain stem
dysfunction, and there is written informed consent by a parent or guardian.
According to the randomization, patients will receive an initial loading dose followed by a
maintenance infusion, of either Mg or identical placebo for 72 hours; all staff involved in
patient care will remain unaware of the treatment allocation, but staff from another
department will monitor Mg blood levels to ensure safety and adequate dosing. A total of 190
patients (95 in each arm) will be recruited.
Phase:
Phase 2
Details
Lead Sponsor:
Oxford University Clinical Research Unit, Vietnam
Collaborators:
Children's Hospital Number 1, Ho Chi Minh City, Vietnam Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam