Abstract:
Background: The World Health Organization (WHO) rehydration management
guidelines (Plan C) for children with acute gastroenteritis (AGE) and severe
dehydration are widely practiced in resource-poor settings, yet have never
been formally evaluated in a clinical trial. A recent audit of outcome of AGE at
Kilifi County Hospital, Kenya noted that 10% of children required high
dependency care (20% mortality) and a number developed fluid-related
complications. The fluid resuscitation trial, FEAST, conducted in African
children with severe febrile illness, demonstrated higher mortality with fluid
bolus therapy and raised concerns regarding the safety of rapid intravenous
rehydration therapy. Those findings warrant a detailed physiological study of
children’s responses to rehydration therapy incorporating quantification of
myocardial performance and haemodynamic changes.
Methods: GASTRO is a multi-centre, unblinded Phase II randomised controlled
trial of 120 children aged 2 months to 12 years admitted to hospital with severe
dehydration secondary to AGE. Children with severe malnutrition, chronic
diarrhoea and congenital/rheumatic heart disease are excluded. Children will
be enrolled over 18 months in 3 centres in Kenya and Uganda and followed
until 7 days post-discharge. The trial will randomise children 1:1 to standard
rapid rehydration using Ringers Lactate (WHO plan ‘C’ – 100mls/kg over 3-6
hours according to age, plus additional 0.9% saline boluses for children
presenting in shock) or to a slower rehydration regimen (100mls/kg given over
8 hours and without the addition of fluid boluses). Enrolment started in
November 2016 and is on-going. Primary outcome is frequency of adverse
events, particularly related to cardiovascular compromise and neurological sequelae. Secondary outcomes focus on clinical, biochemical, and
physiological measures related to assessment of severity of dehydration, and
response to treatment by intravenous rehydration.
Discussion: Results from this pilot will contribute to generating robust
definitions of outcomes (in particular for non-mortality endpoints) for a larger
Phase III trial.
