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© Qui et al. 2016. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background

Over the last 15 years, hand, foot, and mouth disease (HFMD) has emerged as a major public health burden across the Asia-Pacific region. A small proportion of HFMD patients, typically those infected with enterovirus 71 (EV71), develop brainstem encephalitis with autonomic nervous system (ANS) dysregulation and may progress rapidly to cardiopulmonary failure and death. Although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a number of children still deteriorate despite this treatment. Magnesium sulfate (MgSO4) is a cheap, safe, and readily available medication that is effective in managing tetanus-associated ANS dysregulation and has shown promise when used empirically in EV71-confirmed severe HFMD cases.

Methods/Design

We describe the protocol for a randomized, placebo-controlled, double-blind trial of intravenous MgSO4 in Vietnamese children diagnosed clinically with HFMD plus ANS dysregulation with systemic hypertension. A loading dose of MgSO4 or identical placebo is given over 20 min followed by a maintenance infusion for 72 h according to response, aiming for Mg levels two to three times the normal level in the treatment arm. The primary endpoint is a composite of disease progression within 72 h defined as follows: development of pre-specified blood pressure criteria necessitating the addition of milrinone, the need for ventilation, shock, or death. Secondary endpoints comprise these parameters singly, plus other clinical endpoints including the following: requirement for other inotropic agents; duration of hospitalization; presence of neurological sequelae at discharge in survivors; and neurodevelopmental status assessed 6 months after discharge. The number and severity of adverse events observed in the two treatment arms will also be compared. Based on preliminary data from a case series, and allowing for some losses, 190 patients (95 in each arm) will allow detection of a 50 % reduction in disease progression with 90 % power at a two-sided 5 % significance level.

Discussion

Given the large numbers of HFMD cases currently being seen in hospitals in Asia, if MgSO4 is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications, this finding would be important to pediatric care throughout the region.

Trial registration

ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 August 2013).

Details

Title
Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial
Author
Qui, Phan Tu 1 ; Khanh, Truong Huu 2 ; Trieu, Huynh Trung 3 ; Giang, Phạm Thanh 3 ; Bich, Nguyen Ngọc 3 ; Thoa, Le Phan Kim 2 ; Nhan, Le Nguyen Thanh 2 ; Sabanathan, Saraswathy 4 ; Van Doorn, Rogier 4 ; Toan, Nguyen Duc 5 ; Merson, Laura 4 ; Dung, Nguyen Thi Phuong 5 ; Khanh, Lam Phung 5 ; Wolbers, Marcel 4 ; Hung, Nguyen Thanh 6 ; Chau, Nguyen Van Vinh 3 ; Wills, Bridget 4 

 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (GRID:grid.414273.7); Hospital for Tropical Diseases, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (GRID:grid.414273.7) 
 Children’s Hospital Number 1, Ho Chi Minh City, Vietnam (GRID:grid.414273.7) 
 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (GRID:grid.414273.7) 
 Hospital for Tropical Diseases, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (GRID:grid.414273.7); Oxford University, Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford, UK (GRID:grid.4991.5) (ISNI:0000000419368948) 
 Hospital for Tropical Diseases, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (GRID:grid.414273.7) 
 Children’s Hospital Number 1, Ho Chi Minh City, Vietnam (GRID:grid.4991.5) 
Pages
98
Publication year
2016
Publication date
Dec 2016
Publisher
BioMed Central
e-ISSN
17456215
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2795235137
Copyright
© Qui et al. 2016. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.