Magnesium Sulphate for Severe Hand, Foot and Mouth Disease in Vietnam

• Status: Completed
• Trial end date: 2016-12-28
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

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
• Treatments: Magnesium Sulfate

Criteria

Inclusion Criteria:

• Age 6 months to 15 years

• Clinical suspicion of HFMD requiring PICU/HDU admission

• Considered severe enough to warrant invasive blood pressure monitoring by PICU/HDU staff

• Development of hypertension defined as follows:

• For children aged 1 year and over, at least 3 consecutive systolic blood pressure recordings above the 95th centile for age, gender and length (USA guidelines for defining Stage 1 hypertension in children, (Appendix 2)) measured invasively over a period of 20 minutes provided the child is not distressed or crying [30, 31].

• For children aged 6 months to 1 year, systolic BP > 100 mm Hg measured invasively on at least 3 occasions over a period for 20 minutes provided the child is not distressed or crying

• Plus one or more of the following criteria:

• Tachypnoea for age

• Irregular or labored breathing, but with SpO2 above 92% in air and normal ABG (pH, pCO2, pO2, HCO3 all within the normal range for the local laboratory)

• Resting heart rate > 150 bpm

• Mottled skin

• Profuse sweating

• Refractory fever

• Hyperglycemia

• Informed consent

Exclusion Criteria:

• Past history of hypertension, chronic renal, cardiac or pulmonary disease, or any neurological disorder

• Hypertensive emergency

• Already commenced milrinone or any other inotropic agents

• Respiratory distress with SpO2<92% in air or PaCO2>45 mm Hg

• AV block or any arrhythmia

• Acute renal failure