Clinical trial NCT01940250: Magnesium Sulphate for Severe Hand, Foot and Mouth Disease in Vietnam
Official title: A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Magnesium Sulfate for the Management of Severe Hand, Foot and Mouth Disease With Autonomic Nervous System Dysregulation in Vietnamese Children.
Conditions: Hand, Foot and Mouth Disease
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.
Interventions:
description: MgSO4 IV infusion
name: Magnesium Sulphate
other_name: magnesi sulfat krabi 15%
type: Drug
description: H2O IV infusion
name: Sterile water
type: Drug
Study arms:
design_group_description: Sterile water will be packaged identically to the active comparator.<br/>Each patient randomized to the placebo arm of the trial will receive a loading dose of 0.5ml/kg intravenous over 20 minutes , followed by a maintenance dose of 0.3 ml/kg/hr to 0.5 ml/kg/hr randomly adjusted by an independent doctor to mimic adjustments made in the active comparator arm for 72 hrs.
design_group_title: Sterile water
design_group_type: Placebo Comparator
design_group_description: Each patient randomized to the treatment arm of the trial will receive a loading dose of 50mg/kg intravenous over 20 minutes (0.5ml/kg), followed by a maintenance dose of 30-50 mg/kg/hr (0.3 ml/kg/hr to 0.5 ml/kg/hr) for 72 hrs.<br/>The maintenance dose will be determined by increasing the loading infusion dose 0.1 ml/kg/hr (10mg/kg/hr) every 15 minutes to a maximum dose of 0.5 ml/kg/hr (50 mg/kg/hr), with the following caveats:<br/>* If the systolic BP decreases to < 90th percentile for age, gender and length the dose will be reduced by 1 stage every 15 mins<br/>* If the systolic BP increases to the levels detailed in the study protocol for treatment failure, action will be taken as indicated<br/>* If the systolic BP decrease rapidly more than 25% over 15 minutes<br/>* If the plasma Mg level > 2.5 mmol/l or < 1.8 mmol/l a 25% increase or decrease in the infusion rate will be implemented as appropriate.
design_group_title: Magnesium sulphate
design_group_type: Active Comparator
Sponsor: Clinical Trial Service Unit
Collaborators: Childrens Hospital 1
Drug name mappings:
name: 硫酸镁
lang: CN
name: Magnesium Sulfate
lang: EN
name: 硫酸マグネシウム水和物
lang: JP