Plain English Summary
Background and study aims
Shock is a life-threatening condition that occurs when the body is not getting enough blood flow. Timely and rapid infusion of isotonic fluids is the mainstay for the treatment of shock in children worldwide. The World Health Organization (WHO) recommends infusion of isotonic fluids within the first hour for resuscitation in shock for well-nourished children, and further rehydration (with Ringers Lactate) over 3-5 hours for those with severe dehydration. This is in agreement with other guidelines. However, the same WHO guidelines propose infusion of a lower volume of hypotonic fluid at a slower rate of infusion for the treatment of shock in children with severe malnutrition. The evidence for both of these guidelines is very weak. This study aims to look at the safety and tolerability of modern paediatric critical care standard approaches to managing shock compared to the current standard approach advocated by the WHO.
Who can participate?
Children aged over 6 months with severe malnutrition who are admitted to hospital with or develop shock.
What does the study involve?
Children with shock associated with diarrhoea are randomly allocated to be treated with one of two types of fluid infusion: either Ringers’ Lactate or standard WHO management (half strength Darrow’s Solution in 5% dextrose). Children with shock but without diarrhoea are randomly allocated to be treated with one of three types of fluid infusion: either 4.5% albumin, Ringers’ Lactate or standard WHO management (half strength Darrow’s solution in 5% dextrose and followed by blood transfusion for non-responders) .
What are the possible benefits and risks of participating?
Children will be closely monitored and fluids will be given cautiously. Each child will be clinically reassessed after each bolus. Further fluids would be withheld from children showing signs of cardiogenic shock or fluid overload.
Where is the study run from?
KEMRI Centre for Geographic Medicine Research (Coast) at Kilifi District Hospital (KDH), Kenya
When is the study starting and how long is it expected to run for?
January 2007 to February 2009
Who is funding the study?
Wellcome Trust MOP to KEMRI-Wellcome Trust Programme
Who is the main contact?
Professor Kathryn Maitland
k.maitland@imperial.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Kathryn Maitland
ORCID ID
Contact details
PO Box 230
Kilifi
80108
Kenya
+254 (0)41 522535
k.maitland@imperial.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SSC 805
Study information
Scientific title
Phase II safety studies of volume expansion in children with severe malnutrition and features of hypovolaemia
Acronym
FIM
Study hypothesis
We aim to examine the safety and tolerability of current World Health Organization (WHO) fluid management regime and compare these to commonly employed resuscitation protocols used in modern paediatric critical care. Our null hypothesis would anticipate that there would be no difference between these protocols in correction of shock.
Ethics approval
Kenya Medical Research Institute (KEMRI)/National Ethical Review Committee, 25/08/2006
Study design
Single-centre randomised open-label controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Malnutrition and hypovolaemia
Intervention
Treatment will occur at the Site-Kilifi District Hospital, Kenya.
Randomisation group A: children with diarrhoea - history of acute diarrhoea (greater than 6 watery stools/day) plus a feature of shock (see inclusion criteria). Two fluid resuscitation intervention arms:
1. Ringers' lactate
2. Standard WHO management (using half-strength Darrow's Solution in 5% dextrose)
Randomisation group B: shock without diarrhoea. Three fluid resuscitation intervention arms:
1. 4.5% albumin
2. Ringers' lactate
3. Standard WHO management (using half-strength Darrow's solution in 5% dextrose and followed by blood transfusion for non-responders)
Volume of resuscitation fluid used:
1. Human albumin and Ringer's Lactate: 10 ml/kg or 20 ml/kg if child is hypotensive. Total volumes of fluid given depends on resolution of clinical features of shock
2. Half-strength Darrow's: 15 ml/kg over 1 hour. Further bolus of 15 ml/kg over 1 hour if child responds to fluid. If no response/deterioration, then given 10 ml/kg of whole blood over 3 hours
Intervention type
Drug
Phase
Phase II
Drug names
Ringers' lactate, Darrow's solution, albumin
Primary outcome measure
Resolution of features of shock at 4 hours.
Secondary outcome measures
1. In-hospital death
2. Development of serious adverse events such as pulmonary oadema and raised intracranial pressure
Overall trial start date
01/01/2007
Overall trial end date
15/02/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Children greater than 6 months (either sex) with severe malnutrition defined as (one of the following):
1.1. Weight for height z score less than -3 or weight for height percentile (WAP) less than 70%
1.2. Mid-Upper Arm Circumference (MUAC) less than 11.0 cm
1.3. Oedema involving at least both feet (kwashiorkor)
2. Children who are admitted with, or develop during the course of admission, one or more of the following features of compensated or decompensated shock:
2.1. Depressed conscious state: prostration (inability to sit up) or coma (inability to localise a painful stimulus)*
2.2. Bradycardia (heart rate less than 80 beats per minute)
2.3. Evidence of shock or dehydration:
2.3.1. Capillary refill time greater than 2 seconds
2.3.2. Temperature gradient (from lower to upper part of leg elicited by running hand up the shin)
2.3.3. Weak pulse volume or systolic blood pressure less than 80 mmHg
2.3.4. Prolonged capillary refill greater than 2 seconds
2.4. Deep 'acidotic' breathing
2.5. Creatinine greater than 80 umols/L
*only if still present after correction of hypoglycaemia
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. Children of families who decline to consent
2. Haemoglobin less than or equal to 5 g/dl
3. Features of pulmonary oedema (defined as clinical evidence for presence of fine crepitations in both lungs plus oxygen saturations less than 90% in air)
4. Evidence of raised intracranial pressure (brain stem features of coning, systolic blood pressure greater than 90% centile for age plus falling heart rate and/or papilloedema)
5. Known congenital heart disease
Recruitment start date
01/01/2007
Recruitment end date
15/02/2009
Locations
Countries of recruitment
Kenya
Trial participating centre
PO Box 230
Kilifi
80108
Kenya
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
Oxford Mutual Ltd
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 (0)1865 270158
Graham.Waite@admin.ox.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
This trial is run as part of the Wellcome-KEMRI Research Programme:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Kenya Medical Research Institute (KEMRI)/Centre for Geographic Medicine Research Coast (Kenya)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Wellcome Trust (UK) (grant ref: 077092)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20923577
Publication citations
-
Results
Akech SO, Karisa J, Nakamya P, Boga M, Maitland K, Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia., BMC Pediatr, 2010, 10, 71, doi: 10.1186/1471-2431-10-71.