Protocol No: ECCT/16/09/01 Date of Protocol: 26-08-2016

Study Title:

Gastroenteritis Aggressive versus Slow Treatment for RehydatiOn (GASTRO): A Pilot rehydration study for severe dehydration: WHO plan C versus slower rehydration

Study Objectives:
Laymans Summary:
Abstract of Study:

The current WHO rehydration management guidelines (Plan C) for children with gastroenteritis and severe dehydration are widely practiced in resource-poor settings, despite never having been tested in a clinical trial. A recent audit of outcome of acute gastroenteritis (AGE) at Kilifi County Hospital, Kenya noted that 10% children with gastroenteritis required high dependency care managed on WHO Plan C protocol (mortality up to 20%) and a number developed fluid-related complications such as signs of cardiovascular collapse or neurological compromise. The fluid resuscitation trial, FEAST, conducted in children with severe febrile illness raised concerns regarding the safety of rapid intravenous rehydration therapy in other illnesses such as acute gastroenteritis and warrants more detailed examination for assessment and quantification of myocardial performance indices and haemodynamic response to therapy using non-invasive echocardiography imaging.  We therefore proposed a pilot Phase II study to evaluate initial fluid management in children admitted to hospital with severe dehydration secondary to gastroenteritis. We will compare standard aggressive rehydration (WHO plan ‘C’ – 100mls/kg over 3 hours, plus boluses for those with shock) versus a slower rehydration regimen (given over 8 hours). Formal sample sizes have not been calculated for this in-depth pilot study. We aim to study 80 children in total (40 in each arm), which is realistic to obtain an idea about major adverse effects. It is also realistic given the timeframe and funding available for the study.  The focus of this pilot is firstly to document adverse events, particularly related to cardiovascular compromise and neurological sequelae and secondly, to gather a series of useful clinical, biochemical, and physiological data on initial assessment of severity of dehydration, and response to treatment of children by intravenous (IV) rehydration. Results from this pilot will contribute to generating robust definitions of outcomes for a larger phase III trial (in particular for non-mortality endpoints). 

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The current WHO rehydration management guidelines (Plan C) for children with gastroenteritis and severe dehydration are widely practiced in resource-poor settings, despite never having been tested in a clinical trial. A recent audit of outcome of acute gastroenteritis (AGE) at Kilifi County Hospital, Kenya noted that 10% children with gastroenteritis required high dependency care managed on WHO Plan C protocol (mortality up to 20%) and a number developed fluid-related complications such as signs of cardiovascular collapse or neurological compromise. The fluid resuscitation trial, FEAST, conducted in children with severe febrile illness raised concerns regarding the safety of rapid intravenous rehydration therapy in other illnesses such as acute gastroenteritis and warrants more detailed examination for assessment and quantification of myocardial performance indices and haemodynamic response to therapy using non-invasive echocardiography imaging.  We therefore proposed a pilot Phase II study to evaluate initial fluid management in children admitted to hospital with severe dehydration secondary to gastroenteritis. We will compare standard aggressive rehydration (WHO plan ‘C’ – 100mls/kg over 3 hours, plus boluses for those with shock) versus a slower rehydration regimen (given over 8 hours). Formal sample sizes have not been calculated for this in-depth pilot study. We aim to study 120 children in total (60 in each arm), which is realistic to obtain an idea about major adverse effects. It is also realistic given the timeframe and funding available for the study.  The focus of this pilot is firstly to document adverse events, particularly related to cardiovascular compromise and neurological sequelae and secondly, to gather a series of useful clinical, biochemical, and physiological data on initial assessment of severity of dehydration, and response to treatment of children by intravenous (IV) rehydration. Results from this pilot will contribute to generating robust definitions of outcomes for a larger phase III trial (in particular for non-mortality endpoints).