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.

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.

Publications

10 25 50
 
Description Acute Dialysis Quality Initiative (ADQI) consensus conference Fluid management in critical illness
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact The delegates of the 12th Acute Dialysis Quality Initiative (ADQI) Conference sought to obtain consensus on the use of i.v. fluids with the aim of producing guidance for their use. The reviewed a recently proposed model for fluid therapy in severe sepsis and propose a framework by which it could be adopted for use in most situations where fluid management is required. Considering the dose-effect relationship and side-effects of fluids, fluid therapy should be regarded similar to other drug therapy with specific indications and tailored recommendations for the type and dose of fluid. By emphasizing the necessity to individualize fluid therapy, we hope to reduce the risk to our patients and improve their outcome
URL http://www.ncbi.nlm.nih.gov/pubmed/25204700
 
Description Citation in 'A critique of fluid bolus resuscitation in severe sepsis'
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
URL http://www.ncbi.nlm.nih.gov/pubmed/22277834
 
Description Citation in Review of Resuscitation Fluids in NEJM
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
URL http://www.ncbi.nlm.nih.gov/pubmed/24350966
 
Description Cited in Guideline: updates on paediatric emergency triage, assessment and treatment: care of critically-ill children. WHO 2016
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
 
Description Consensus Round Table Symposium on Fluid resuscitation
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
 
Guideline Title Draft recommendations for management of children with severe febrile illness and impaired circulation without signs of severely impaired circulation
Description East Africa Guidelines Panel Recommendations
Geographic Reach Africa 
Policy Influence Type Citation in clinical guidelines
 
Description Fluid resuscitation in children
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
Impact Medicine Sans Frontieres commissioned this review and changed their treatment guidelines for fluid resuscitation in children
URL http://www.ncbi.nlm.nih.gov/pubmed/22952819
 
Description Membership of Technical Expert Group for Severe Malaria
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Fluid management of severe malaria in children has been informed by the publication of the FESAT trial. The TEG is currently (Nov 2013) undertaking a revision of management guidelines (to be published in 2015). WHO will consider recommendation made by this review committee whilst revising current guidelines.
 
Description Multiple Commentaries and Reviews of FEAST trial result
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
 
Description Systematic Review of Fluid resuscitation in children
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
Impact Medicine Sans Frontiere changed guidelines
 
Guideline Title Severe Malaria
Description WHO 2014 severe malaria guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Fluid resuscitation is not longer recommended for children with severe malaria- leading to the saving of many lives worldwide.
URL http://www.ncbi.nlm.nih.gov/pubmed/25214480
 
Description WHOETAT: Management of Severe Illness in Resource-poor hospitals
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
URL http://www.ncbi.nlm.nih.gov/pubmed/24462328
 
Description Alexander Flemming Dissemination Grant
Amount £30,000 (GBP)
Funding ID C0395 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2012 
End 11/2013
 
Description Global Health Trials
Amount £2,747,308 (GBP)
Funding ID G0801439 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2008 
End 07/2011
 
Description Major Overseas Programme Grant
Amount £45,000,000 (GBP)
Funding ID 203077/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2021
 
Description Project Grant
Amount $1,200,000 (AUD)
Funding ID APP1061382 
Organisation National Health and Medical Research Council 
Sector Public
Country Australia
Start  
 
Description Wellcome Collaborative Award in Science
Amount £3,944,185 (GBP)
Funding ID 209265/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2018 
End 06/2022
 
Title Development of Open Clinica for multisite trial 
Description Open Clinica an open source database software that was specifically adapted for use in this trial by our programmer/data manager 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Wider appreciation that open source software can be used as a platform for GCP trial and is compliant with FDA standards 
URL http://www.ncbi.nlm.nih.gov/pubmed/21453454
 
Title Pragmatic Deferred Consent Proceedure for research in emergency medicine 
Description FEAST is the largest Phase III paediatric fluid resuscitation trial ever undertaken. To ensure an ethical and humane process to approaching parents- we developed a novel strategy for deferred consent. We were uncomfortable with full consent waiver since this may mean that parents may never get to know that their child was involved in a research study - which if they had known at the time of admission they could have exercised their right to refuse. For the sickest children we opted for, and have ethical approval for, parental verbal assent, where parents understood that their child would be involved in a clinical trial, but the details would be given after recruitment - during informed consent- once their child was stablised. We plan substudies to evaluate this with social sciences groups specializing in research ethics. Our methodology has been written up and recently submitted for publication. 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact The ethical landscape has changed so vastly such that any pragmatic consenting process giving the key sensitivities to parents so they can weigh up risks and benefits contextually is now a rare phenomenon. Having presented the FEAST trial at international paediatric critical care conferences and more recently in a meningitis meeting - our consent process was welcomed as practical and helpful example by paediatricians who are struggling with European ICH GCP legislation. There have been two important regulatory developments in recent years. Firstly, in January 2007 EU paediatric medicine regulation (Regulation (EC) No 1901/2006) requiring all new license applications to include paediatric data. Followed by the December 2006 amendment to the EU trials directive that was intended to enable research in emergencies. Recent reports suggest this is not working in practice. The new requirement for research in children is compounded by the lack of guidance for conducting studies in this setting. FEAST trial consent process therefore sets a benchmark for future paediatric trials. 
URL http://www.ncbi.nlm.nih.gov/pubmed/23408950
 
Title FEAST trial database 
Description Open Clinica was used a platform for this database 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Multiple papers have resulted from this database, and has feed into chapters in at least 2 Phds. The database will eventually become open access 
 
Description Human Genetics 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution Basic science investigation for FEAST trial and planned investigation in TRACT trial
Collaborator Contribution Design of basic science investigation
Impact Laboratory strengthening at Mbale Regional Referral Hospital, Eastern Uganda Multi-disciplinary: medical, immunology, molecular, genetics
Start Year 2011
 
Description Malaria Consortium_ FEAST trial extension 
Organisation Malaria Consortium Africa, Kampala
Country Uganda 
Sector Charity/Non Profit 
PI Contribution THe FEAST trial was re-located from Ghana, The Gambia to Uganda and Teule, Tanzania. Linking to 4 sites in Uganda was made possible through a new collaboration with Malaria Consortium in partnership with our research team. Collaborators and co applicant added to extension (GO801439).
Collaborator Contribution Hosting of the FEAST management team and monitors. Financial and logistic management of 4 trial sites
Impact Extension of FEAST trial (G0801439) Setting up of 3 new trial sties for research- required a multi disciplinary team.
Start Year 2007
 
Description Mbale Clinical Research Institute, Mbale, Uganda 
Organisation Mbale Clinical Research Institute
Country Uganda 
Sector Hospitals 
PI Contribution The Wellcome Trust has funded MCRI as part of the Major Overseas Award to Oxford-Kemri Wellcome Trust Programme. The collaboration is led by Programme members working with the Director of the Mbale Clinical Research Unit. We have established a strong relationship with MCRI having supported his PhD studies and his transition from a clinical and managerial career to a research career.
Collaborator Contribution Over the last 3 years Mbale has established a track record of clinical trials, receiving subcontracts for £996k and £812k in the last 3 years (subcontracted from the £3.2M and £2.4M awards for the TRACT and COAST trials) and recent award from MRC for a Phase II study of antibiotic treatment targeting non-typhoidal salmonellae (TABS).
Impact Award of a subcontract from the KEMRI Wellcome Trust Programme for £1.5 Million in 2016. The building of a new research laboratory to strengthen diagnostic and molecular research. The will enable the centre to expand its research portfolio in future.
Start Year 2016
 
Description Mbale and Soroti Hospitals- Wellcome Trust Collaboration 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution These previously research naïve hospitals were brought into the FEAST trial by the PI working in parntership with Malaria Consortium, Uganda. The site PIs have worked with the FEAST team to develop a clinical research platform to study acute malaria, which remains the major cause of admission. Comparative studies with Kilifi offer new potential insights into disease pathogenesis.
Collaborator Contribution Development of a clinical research team and undertaken a number of substudies A new laboratory will be built in the 2104, supported by Imperial College
Impact Routine clinical surveillance is due to be introduced and already a number of sub studies of life threatening childhood infections within FEAST have provided collaborative links with the KEMRI Wellcome Trust Programme. These include studies of pathogenesis (immunology and pathogen biology groups), evaluation of community perceptions of the consent process developed for FEAST, case control genetic studies and new biomarkers for severe malaria. A number of these studies are being conducted by the PI from Mbale who is registered on KEMRI Open University PhD programme.
Start Year 2008
 
Description Mbale and Soroti Hospitals- Wellcome Trust Collaboration 
Organisation Mbale Regional Hospital
Country Uganda 
Sector Hospitals 
PI Contribution These previously research naïve hospitals were brought into the FEAST trial by the PI working in parntership with Malaria Consortium, Uganda. The site PIs have worked with the FEAST team to develop a clinical research platform to study acute malaria, which remains the major cause of admission. Comparative studies with Kilifi offer new potential insights into disease pathogenesis.
Collaborator Contribution Development of a clinical research team and undertaken a number of substudies A new laboratory will be built in the 2104, supported by Imperial College
Impact Routine clinical surveillance is due to be introduced and already a number of sub studies of life threatening childhood infections within FEAST have provided collaborative links with the KEMRI Wellcome Trust Programme. These include studies of pathogenesis (immunology and pathogen biology groups), evaluation of community perceptions of the consent process developed for FEAST, case control genetic studies and new biomarkers for severe malaria. A number of these studies are being conducted by the PI from Mbale who is registered on KEMRI Open University PhD programme.
Start Year 2008
 
Description Medical Research Council Clinical Trials Unit 
Organisation Imperial College London
Department Department of Paediatrics
Country United Kingdom 
Sector Academic/University 
PI Contribution Work leading up the trials, identification of partners, trial sites and design and execution of clinical trials
Collaborator Contribution Design of clinical trials, trial governance and data management, statatistical expertise Multidisciplinary clinical trialists, infectious disease speacialists, health economists and specialists in health policy
Impact FEAST trial Publications Alexander Fleming Award TRACT trial
Start Year 2008
 
Description Medical Research Council Clinical Trials Unit 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution Work leading up the trials, identification of partners, trial sites and design and execution of clinical trials
Collaborator Contribution Design of clinical trials, trial governance and data management, statatistical expertise Multidisciplinary clinical trialists, infectious disease speacialists, health economists and specialists in health policy
Impact FEAST trial Publications Alexander Fleming Award TRACT trial
Start Year 2008
 
Description Medicine Sans Frontiere 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution Design of fluid management studies in severe malnutrition
Collaborator Contribution Protocol development and cofunding for clinical trial
Impact Clinical studies on going in Kenya/Uganda Multidisplinary: clinical trials, critical care, humanitarian health
Start Year 2011
 
Description NIMRI, Teule, Tanzania 
Organisation National Institute for Medical Research, Tanzania
Department Teule Hospital
Country Tanzania, United Republic of 
Sector Hospitals 
PI Contribution Relocation of FEAST to 5 new sites in East AFrica and resubmission of extension (GO801439) with coapplicants from NIMRI
Collaborator Contribution Teule Hospital, through NIMRI joined the FEAST trial
Impact FEAST trial site
Start Year 2007
 
Description POST and COAST trials 
Organisation The Prince Charles Hospital
Department Social Work Department
Country Australia 
Sector Hospitals 
PI Contribution Development and conduct a pilot study (POST) for the main COAST trial
Collaborator Contribution Development of the pilot study (POST) and partnership with Fischer and Paykel
Impact none realised yet
Start Year 2012
 
Description SMAART consortium 
Organisation Wellcome Trust
Department Mahidol University-Oxford Tropical Medicine Research Programme
Country Thailand 
Sector Academic/University 
PI Contribution The main aim of SMAART is to conduct better research studies faster, to improve outcomes from severe malaria. SMAART will act as the operational platform by which future research is planned in a coordinated and reciprocal manner to continuously update disease definitions and treatment guidelines for severe malaria.
Collaborator Contribution To overcome the barriers to achieving this goal, SMAART brings together applicants and co-investigators from three Wellcome Trust major overseas programmes (KEMRI Wellcome Trust Programme, Kenya, Malawi-Liverpool-Wellcome Trust Unit, Malawi (Prof David Lalloo) and Mahidol Oxford Research Unit, Thailand together with African scientists from existing or new collaborations and specialists in clinical trials ( MRC CTU at UCL) and ultimately national and international stakeholders. All are necessary to ensure that the most important questions are identified and combined optimally in the most efficient trial design which is acceptable and relevant to parents, healthcare professionals, ethical review boards and ministries of health. The network is thus a multi-disciplinary team providing complementary expertise and added value including links to other networks. The SMAART consortium encompasses decades of clinical and academic experience, track records of successful high quality research in low-income settings, and significant impact as evidenced by publication citation, grant funding and policy change.
Impact none yet; meeting planned for June 2016 to plan the grant submission to UK funder collaborative award
Start Year 2015
 
Description SMAART consortium 
Organisation Wellcome Trust
Department Malawi-Liverpool Wellcome Trust Clinical Research Programme
Country Malawi 
Sector Charity/Non Profit 
PI Contribution The main aim of SMAART is to conduct better research studies faster, to improve outcomes from severe malaria. SMAART will act as the operational platform by which future research is planned in a coordinated and reciprocal manner to continuously update disease definitions and treatment guidelines for severe malaria.
Collaborator Contribution To overcome the barriers to achieving this goal, SMAART brings together applicants and co-investigators from three Wellcome Trust major overseas programmes (KEMRI Wellcome Trust Programme, Kenya, Malawi-Liverpool-Wellcome Trust Unit, Malawi (Prof David Lalloo) and Mahidol Oxford Research Unit, Thailand together with African scientists from existing or new collaborations and specialists in clinical trials ( MRC CTU at UCL) and ultimately national and international stakeholders. All are necessary to ensure that the most important questions are identified and combined optimally in the most efficient trial design which is acceptable and relevant to parents, healthcare professionals, ethical review boards and ministries of health. The network is thus a multi-disciplinary team providing complementary expertise and added value including links to other networks. The SMAART consortium encompasses decades of clinical and academic experience, track records of successful high quality research in low-income settings, and significant impact as evidenced by publication citation, grant funding and policy change.
Impact none yet; meeting planned for June 2016 to plan the grant submission to UK funder collaborative award
Start Year 2015
 
Description TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children 
Organisation Hospital Pediátrico David Bernardino
Department Department of Paediatrics
Country Angola 
Sector Hospitals 
PI Contribution Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design.
Collaborator Contribution Trial design Trial design
Impact Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011.
Start Year 2010
 
Description TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design.
Collaborator Contribution Trial design Trial design
Impact Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011.
Start Year 2010
 
Description TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children 
Organisation University of Amsterdam
Department Department of Paediatrics
Country Netherlands 
Sector Academic/University 
PI Contribution Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design.
Collaborator Contribution Trial design Trial design
Impact Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011.
Start Year 2010
 
Description TRACT trial :A randomised controlled trial of transfusion and treatment of severe anaemia in African children 
Organisation University of Malawi
Department College of Medicine
Country Malawi 
Sector Academic/University 
PI Contribution Our group have identified that transfusion of African children is a research and treatment priority. We have brought together a number of experts in the field of transfusion and severe anaemia to review the evidence for a transfusion trial and develop a research agenda for this area critical to management of severely-ill children in Africa including a trial which incorporates a factorial design.
Collaborator Contribution Trial design Trial design
Impact Submission of an expression of interest to MRC which has been approved by the Global Health Strategy Board for full submission in March 2011.
Start Year 2010
 
Description Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) 
Organisation Cipla
Country India 
Sector Private 
PI Contribution Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC
Collaborator Contribution Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics
Impact Submission to EDCTP- not funded Preparation of grant for 2013
Start Year 2012
 
Description Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC
Collaborator Contribution Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics
Impact Submission to EDCTP- not funded Preparation of grant for 2013
Start Year 2012
 
Description Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) 
Organisation Radboud University Nijmegen
Department Department of Pharmacology and Toxicology
Country Netherlands 
Sector Academic/University 
PI Contribution Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC
Collaborator Contribution Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics
Impact Submission to EDCTP- not funded Preparation of grant for 2013
Start Year 2012
 
Description Targeting Anti-microbiological treatment in African children with Severe Malaria (TABS) 
Organisation Spectral Diagnostics Inc
Country Canada 
Sector Private 
PI Contribution Development of early phase trial of antimicrobial treatment- submitted to EDCTP and now to submit to MRC
Collaborator Contribution Development of study protocol Industry Donations of product for free (Azithromycin and placebo) and/or diagnostics
Impact Submission to EDCTP- not funded Preparation of grant for 2013
Start Year 2012
 
Description Uganda Blood Transfusion 
Organisation Imperial College London
Department Department of Paediatrics
Country United Kingdom 
Sector Academic/University 
PI Contribution For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites
Collaborator Contribution Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial
Impact TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013
Start Year 2013
 
Description Uganda Blood Transfusion 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites
Collaborator Contribution Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial
Impact TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013
Start Year 2013
 
Description Uganda Blood Transfusion 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites
Collaborator Contribution Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial
Impact TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013
Start Year 2013
 
Description Uganda Blood Transfusion 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution For the purposes of the FEAST and TRACT trial developed new network of clinical trial sites
Collaborator Contribution Blood transfusion services will be critical in this collaboration for the successful conduct of the transfusion componant of the TRACT trial
Impact TRACT trial protocol approval in Uganda Trial started enrolment in Sept 2013
Start Year 2013
 
Description Understanding of pathophysiology of sepsis and the tissue effects of fluid resuscitation and transfusion 
Organisation Critical Care Research Group
Country Australia 
Sector Charity/Non Profit 
PI Contribution Funded Phd student to join the group and conduct research
Collaborator Contribution Awarded a grant as a collaborator; supervision of student; publication output
Impact Multdisciplinary
Start Year 2012
 
Description Clinical Trainer involved in RCPCH ETAT training guidelines 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact As a result of this activity many countries in Africa follow these recommendations i.e. national guidelines rather than the out-dated WHO guidelines
Year(s) Of Engagement Activity 2012,2013,2014
 
Description Consultation: Nuffield Council on Bioethics 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact I was asked to provide my views for Nuffield Council on Bioethics ahead of their consultation on ethical issues arising out of children's involvement in clinical research.

this has not yet happened
Year(s) Of Engagement Activity 2013
 
Description Interviewed by Voice of America about NEJM Severe Malaria Perspective 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact New England Journal Perspective on Severe Malaria in African Children: need for continuing investment. I discussed the slow pace of progress in clinical trials in Africa; yet 10% of children with severe malaria will die. In the drive to eliminate malaria most scientists and policy makers felt that malaria was all but conquered. Many expressed surprise at the burden of disease. Thought published only on 22nd December 2016 the current Altmetrics for this article is 124.
Year(s) Of Engagement Activity 2017
URL http://www.voanews.com/a/death-toll-from-malaria-among-african-children-called-unacceptably-high/366...
 
Description Meeting of African Paediatricians to review fluid resuscitation management policy fo 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Health professionals
Results and Impact A meeting was held in Nairobi, 12th-13th October 2012, to examine the evidence on the use of boluses (rapid fluid resuscitation) for critically sick children in sub-Saharan Africa, and consider the implications of this evidence. The meeting was hosted by the Kenya Paediatric Association, and was attended by paediatricians and other healthcare personnel and researchers from 10 sub-Saharan African countries, as well as members of the FEAST trial team from Africa.

A meta-analysis of all the available evidence on fluid resuscitation for these children was carried out subsequently and has been published; it supports the conclusions of the FEAST trial (see http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043953).

This delegates agreed that the new evidence presented means that international and national guidelines, policy and practice need to change. The recommendations should no longer be that children with febrile illness (due to malaria and/or sepsis including presumptive diagnoses) and impaired perfusion, and/or impaired consciousness and/or respiratory distress should be given fluid boluses (ie giving fluids rapidly over a short period of time). Instead it should be recommended that maintenance fluids should be given slowly at 4ml/hour to replace fluid losses.

A number of hospitals (including those involved in the trial) and Medicins Sans Frontiers have already changed their practice in the light of these results, but other international and national organisations and institutions have been slower to change, due in part to lack of guidance from the World Health Organisation.

At the conclusion of the workshop the delegates indicated that it was clear to them from the published evidence and further discussions of evidence presented at the meeting that international (WHO) and national guidelines, policy and practice need to change.
Year(s) Of Engagement Activity 2012
URL http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043953
 
Description Radio_Interview BBC 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact In 2015 I was interviewed for BBC World Service Life Changers by Kevin Fong (Discovery-20150831-LifeChangersKathrynMaitland.mp3)
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/programmes/p030mb5n
 
Description Visit to WHO 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact WHO have the full results of trial (published and unpublished) as well as policy brief.
They are currently conducting a review of the evidence before the consider changing their guidelines

WHO are the key policy maker who advise on guidelines for management of children in LED countries including Africa. FEAST will direct inform policy

WHO not yet changed policy further meeting with study investigators in 2012
Year(s) Of Engagement Activity 2010,2012