Fluid Expansion As Supportive Therapy in critically ill African children (FEAST)
Lead Research Organisation:
Imperial College London
Department Name: Dept of Medicine
Abstract
FEAST trial is a large randomised controlled trial in African children with severe illness examining whether the addition of rapid fluid infusion at hospital admission to standard case management improves survival compared to standard management alone.
In sub-Saharan Africa case fatality rates in hospital for severe infections in children remains at 15-30%. In this region well over a million children die of severe infection in hospital each year. Currently, antimalarial and antimicrobial drugs are the mainstay of treatment, however most deaths occur early, due to the complications of severe illness, and before definitive treatments have time to act. In this situation doctors have to rely upon supportive therapies to treat complications to try to improve outcome. Defining which are the best life-saving treatments has been frustrated by the lack of clinical studies.
Rapid fluid infusion to correct fluid deficits is a standard supportive treatment and practised routinely for the emergency management of children with severe illness. Currently, reticence to adopt this approach remains and thus in African hospitals children are managed with little fluid or no additional fluid. If the benefits of rapid fluid infusion were shown, then FEAST trial could potentially save thousands of lives of young children annually.
In sub-Saharan Africa case fatality rates in hospital for severe infections in children remains at 15-30%. In this region well over a million children die of severe infection in hospital each year. Currently, antimalarial and antimicrobial drugs are the mainstay of treatment, however most deaths occur early, due to the complications of severe illness, and before definitive treatments have time to act. In this situation doctors have to rely upon supportive therapies to treat complications to try to improve outcome. Defining which are the best life-saving treatments has been frustrated by the lack of clinical studies.
Rapid fluid infusion to correct fluid deficits is a standard supportive treatment and practised routinely for the emergency management of children with severe illness. Currently, reticence to adopt this approach remains and thus in African hospitals children are managed with little fluid or no additional fluid. If the benefits of rapid fluid infusion were shown, then FEAST trial could potentially save thousands of lives of young children annually.
Technical Summary
Over a million children are estimated to die from severe malaria annually, with most deaths occurring in African children under 5 years of age. Despite the availability of effective antimalarial drugs, 20-30% of children admitted to hospital with severe malaria die, usually within the first 24 hours following admission. Reduction in the early in-hospital mortality from severe childhood malaria in Africa is likely to depend on the application of simple interventions to correct the disordered physiology leading to death.
Correction of fluid deficits by rapid infusion (volume expansion) is practised routinely for sick children presenting for emergency care and would be a logical supportive treatment for children with severe malaria with signs of dehydration or shock. There is no consensus regarding best practice in this situation. Clinical management varies across Africa, some centres restricting fluids to maintenance only, while others administer whole blood, despite concerns regarding cost and the risks of transfusion-acquired infection. Haemodynamic studies have recently established that hypovolaemia is common in children with malaria complicated by acidosis, and the results of three trials indicate that volume expansion, particularly with albumin, is associated with a lower mortality than that observed using maintenance fluids alone. However, opinion on this perspective remains divided, and the current WHO guidelines are unclear on the extent, importance and required treatments for the volume deficits.
To resolve this uncertainty we aim to establish definitively, through a multicentre, partially masked, randomised controlled trial, whether volume expansion using either saline or albumin results in a lower mortality than low volume maintenance fluids only (the current standard practise in most hospitals) in 1650 children with severe malaria complicated by acidosis. Interventions will be administered within 2 hours of admission. Mortality will be the primary outcome. Secondary outcomes will include adverse events (development of decompensated shock, pulmonary oedema or signs of raised intracranial pressure) and residual neurological deficits assessed at discharge and at 6 months.
As the study will be conducted at three sites in Africa, with different malaria endemicity, using largely bedside criteria to enrol children, the results of the trial will be generalisable and as such would form the basis for future international treatment recommendations. Furthermore a cost-effectiveness analysis will be undertaken, comparing each of the two interventions with conventional treatment, which will enable future policy decisions to be based on firm economic data.
Correction of fluid deficits by rapid infusion (volume expansion) is practised routinely for sick children presenting for emergency care and would be a logical supportive treatment for children with severe malaria with signs of dehydration or shock. There is no consensus regarding best practice in this situation. Clinical management varies across Africa, some centres restricting fluids to maintenance only, while others administer whole blood, despite concerns regarding cost and the risks of transfusion-acquired infection. Haemodynamic studies have recently established that hypovolaemia is common in children with malaria complicated by acidosis, and the results of three trials indicate that volume expansion, particularly with albumin, is associated with a lower mortality than that observed using maintenance fluids alone. However, opinion on this perspective remains divided, and the current WHO guidelines are unclear on the extent, importance and required treatments for the volume deficits.
To resolve this uncertainty we aim to establish definitively, through a multicentre, partially masked, randomised controlled trial, whether volume expansion using either saline or albumin results in a lower mortality than low volume maintenance fluids only (the current standard practise in most hospitals) in 1650 children with severe malaria complicated by acidosis. Interventions will be administered within 2 hours of admission. Mortality will be the primary outcome. Secondary outcomes will include adverse events (development of decompensated shock, pulmonary oedema or signs of raised intracranial pressure) and residual neurological deficits assessed at discharge and at 6 months.
As the study will be conducted at three sites in Africa, with different malaria endemicity, using largely bedside criteria to enrol children, the results of the trial will be generalisable and as such would form the basis for future international treatment recommendations. Furthermore a cost-effectiveness analysis will be undertaken, comparing each of the two interventions with conventional treatment, which will enable future policy decisions to be based on firm economic data.
