Randomised trial of fluid resuscitation strategies in African children with severe febrile illness & impaired perfusion
Lead Research Organisation:
Imperial College London
Department Name: Dept of Medicine
Abstract
In hospitals throughout sub-Saharan Africa case fatality rates for severe infections in childhood 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 and try to improve outcome. Defining which are the best life saving treatments has been frustrated by the lack of clinical trials addressing this issue.
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 African children with severe illness and signs of impaired perfusion. Currently, reticence to adopt this approach remains and so most children are managed with little or no additional fluid. In these circumstances the method resolving uncertainty is though in a clinical trial.
FEAST is a multi centre study which aims to address this question and to definitively establish whether volume expansion with saline or albumin improves disability-free survival and whether this is best achieved by saline, a cheap a widely used solution or the more expensive colloid, albumin (a safe bi-product of a blood transfusion).
If benefit were shown it could potentially save thousands of lives of young children annually. Preliminary analysis suggest that this represents a highly cost effective method for improving child survival and which could be easily adopted within future international guidelines for treating children with severe illness and signs of impaired perfusion.
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 African children with severe illness and signs of impaired perfusion. Currently, reticence to adopt this approach remains and so most children are managed with little or no additional fluid. In these circumstances the method resolving uncertainty is though in a clinical trial.
FEAST is a multi centre study which aims to address this question and to definitively establish whether volume expansion with saline or albumin improves disability-free survival and whether this is best achieved by saline, a cheap a widely used solution or the more expensive colloid, albumin (a safe bi-product of a blood transfusion).
If benefit were shown it could potentially save thousands of lives of young children annually. Preliminary analysis suggest that this represents a highly cost effective method for improving child survival and which could be easily adopted within future international guidelines for treating children with severe illness and signs of impaired perfusion.
Technical Summary
In hospitals throughout sub-Saharan Africa (SSA) case fatality rates for severe infections in childhood remains at 15-30%. Curently, 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 and try to improve outcome. Defining which are the best life saving treatments has been frustrated by the lack of clinical trials addressing this issue.
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 illness with signs of impaired perfusion. Opinion of this perspective remains divided. Reticence to adopt this approach remains and thus in African hospitals children are managed with little fluid or no additional fluid or with blood transfusion despite the concerns over cost and long-term risk of infection.
The FEAST trial is a large pragmatic randomised controlled trial in African children at 6 hospitals in SAA. It aims to address the question of whether the addition of fluid resuscitation to the standard case management to rapidly restore intravascular volume depletion of African children with severe febrile illness and clinical evidence of impaired perfusion is safe and results in improved survival compared to standard management alone. More specifically, the trial has been designed with the aim of resolving whether rapid correction of intravascular volume, using colloidal (albumin) or electrolyte solutions (saline), is safe and improves both survival and neurological outcome in children with severe falciparum malaria rather than the slow restoration of total body water deficits suggested by other clinical researchers and currently recommended in international guidelines. Most interventions will be given in the first two hours after admission. Children will be monitored for 48 hours. The primary endpoint is in-hospital mortality at 48 hours post randomisation.
If benefit were shown it could potentially save thousands of lives of young children annually. An initial estimate of cost-effectiveness suggests that albumin would be cost-effective compared to no treatment for a decision maker willingness to pay $35 or $5.33 per life year gained. If albumin were superior to saline or standard of care then investment in translating the newer technologies to large regional blood transfusion services to produce a cheap, regional source of albumin would be necessary.
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 illness with signs of impaired perfusion. Opinion of this perspective remains divided. Reticence to adopt this approach remains and thus in African hospitals children are managed with little fluid or no additional fluid or with blood transfusion despite the concerns over cost and long-term risk of infection.
The FEAST trial is a large pragmatic randomised controlled trial in African children at 6 hospitals in SAA. It aims to address the question of whether the addition of fluid resuscitation to the standard case management to rapidly restore intravascular volume depletion of African children with severe febrile illness and clinical evidence of impaired perfusion is safe and results in improved survival compared to standard management alone. More specifically, the trial has been designed with the aim of resolving whether rapid correction of intravascular volume, using colloidal (albumin) or electrolyte solutions (saline), is safe and improves both survival and neurological outcome in children with severe falciparum malaria rather than the slow restoration of total body water deficits suggested by other clinical researchers and currently recommended in international guidelines. Most interventions will be given in the first two hours after admission. Children will be monitored for 48 hours. The primary endpoint is in-hospital mortality at 48 hours post randomisation.
If benefit were shown it could potentially save thousands of lives of young children annually. An initial estimate of cost-effectiveness suggests that albumin would be cost-effective compared to no treatment for a decision maker willingness to pay $35 or $5.33 per life year gained. If albumin were superior to saline or standard of care then investment in translating the newer technologies to large regional blood transfusion services to produce a cheap, regional source of albumin would be necessary.
