Role of hypovolaemia in the acidosis of severe malaria
| ISRCTN | ISRCTN35536139 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN35536139 |
| Protocol serial number | 062258 |
| Sponsor | Imperial College London (UK) |
| Funder | The Wellcome Trust (UK) (grant ref: 062258) |
- Submission date
- 12/09/2005
- Registration date
- 14/10/2005
- Last edited
- 23/05/2014
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Shock is a medical emergency which occurs when there is not enough blood flow around the body. As a result of tissues not receiving enough oxygen, too much acid builds up in the body (metabolic acidosis). Children with severe malaria often have metabolic acidosis as a complication of shock. The usual treatment for shock is to replenish lost fluid (fluid resuscitation). We have shown previously that human albumin solution (HAS: a by-product of blood transfusion) safely corrects this acidosis and improves the outcome of children with severe malaria complicated by acidosis. HAS is currently expensive and not widely available in Africa. This study aims to examine the safety and dose required for the correction of acidosis of lower cost infusions called colloids: Gelofusine, Dextran 70 and Hetastarch. These will be compared to a control group of children receiving HAS. The results of this study will form the basis for the future larger trials comparing colloidal solutions with saline or maintenance alone, which are required before specific treatment recommendations can be made.
Who can participate?
Children aged over 3 months, either sex, who have severe falciparum malaria (impaired consciousness and or deep breathing) and metabolic acidosis.
What does the study involve?
Children will be randomly allocated to undergo fluid resuscitation with either HAS, Gelofusine, Dextran 70 or Hetastarch.
What are the possible benefits and risks of participating?
Children will be closely monitored and fluid will be administered cautiously.
Where is the study run from?
The study will be based at the 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?
The study started in December 2004 and ended in December 2008.
Who is funding the study?
The Wellcome Trust (UK).
Who is the main contact?
Professor Kathryn Maitland
k.maitland@imperial.ac.uk
Contact information
Scientific
Wellcome Trust Research Unit
CGMR-coast KEMRI
Kilifi
PO Box 230
Kenya
| Phone | +254 (0)415 22063 |
|---|---|
| k.maitland@imperial.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | Role of hypovolaemia in the acidosis of severe malaria: a randomised controlled trial |
| Study objectives | This study adds to and extends the original aims of previous studies. In those we provided new, clear evidence for the presence of hypovolaemia in severe malaria and showed that this could be safely corrected by volume resuscitation with either 0.9% saline or 4.5% human albumin solution (HAS). In a formal randomised controlled trial we showed that volume expansion with albumin was associated with a significantly lower mortality in children with severe malaria acidosis, especially those admitted in coma. As HAS is costly and not available in Africa in this current study we aim to examine the safety and dose required (efficacy) for the correction of hypovolaemia of lower cost colloids: Gelofusine, Dextran 70 and Hetastarch. These will be compared to a control group of children receiving HAS. In this prospective study we aim to enrol children and randomised them to either Gelofusin, Dextran 70, Hetastarch or HAS. The results of this study will form the basis for the future design of multicentre trials comparing colloidal solutions with saline or maintenance alone, which are required before specific treatment recommendations can be made. |
| Ethics approval(s) | Kenya Medical Research Institute (KEMRI) National Scientific Steering Committee and Ethics Review Board, July/August 2004, ref: 864 |
| Health condition(s) or problem(s) studied | Severe falciparum malaria |
| Intervention | Fluid resuscitation with either: 1. Human albumin solution 2. Gelofusine 3. Dextran 70 4. Hetastarch |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Human albumin solution, gelofusine, Dextran 70, Hetastarch |
| Primary outcome measure(s) |
The resolution of clinical features of shock and case fatality |
| Key secondary outcome measure(s) |
Development of major side effects or complications of volume resusciation: |
| Completion date | 31/10/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 3 Months |
| Sex | All |
| Target sample size at registration | 160 |
| Key inclusion criteria | 1. Kenyan children aged more than three months, either sex 2. Clinical features of severe falciparum malaria (impaired consciousness and or deep breathing) 3. Metabolic acidosis (base deficit more than or equal to eight) |
| Key exclusion criteria | 1. Children of families who decline consent 2. Children with: 2.1. Severe anaemia (haemoglobin less than 5 g/dl) 2.2. Cerebrospinal fluid (CSF) changes consistent with meningitis 2.3. Clinical features of pulmonary oedema (defined as clinical evidence presence of fine crepitations in both lungs plus oxygen saturations less than 95%) 2.4. Evidence of raised intracranial pressure (brain stem features of coning, systolic blood pressure more than 90% centile for age plus falling heart rate and/or papilloedema) 2.5. Any conditions that may contraindicate the use of volume replacement, e.g. established renal failure or known congenital heart disease |
| Date of first enrolment | 01/11/2004 |
| Date of final enrolment | 31/10/2006 |
Locations
Countries of recruitment
- Kenya
Study participating centre
PO Box 230
Kenya
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | preliminary results | 15/02/2005 | Yes | No | |
| Results article | results | 15/09/2006 | Yes | No | |
| Results article | results | 01/08/2010 | Yes | No | |
| Other publications | retrospective review | 01/06/2003 | Yes | No |
