Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information



Primary contact

Dr Kathryn Maitland


Contact details

Wellcome Trust Research Unit
PO Box 230
+254 (0)415 22063

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Role of hypovolaemia in the acidosis of severe malaria: a randomised controlled trial


Study hypothesis

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

Kenya Medical Research Institute (KEMRI) National Scientific Steering Committee and Ethics Review Board, July/August 2004, ref: 864

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Severe falciparum malaria


Fluid resuscitation with either:
1. Human albumin solution
2. Gelofusine
3. Dextran 70
4. Hetastarch

Intervention type



Phase II

Drug names

Human albumin solution, gelofusine, Dextran 70, Hetastarch

Primary outcome measures

The resolution of clinical features of shock and case fatality

Secondary outcome measures

Development of major side effects or complications of volume resusciation:
1. Abnormal clotting indices
2. Pulmonary oedema
3. Raised intracranial pressure

Overall trial start date


Overall trial end date


Reason abandoned


Participant 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)

Participant type


Age group




Target number of participants

40 in each group (160 in total)

Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Wellcome Trust Research Unit
PO Box 230

Sponsor information


Imperial College London (UK)

Sponsor details

Prof Mike Levin
Department of Paediatrics and Wellcome Trust Centre for Clinical Tropical Medicine
Faculty of Medicine
Imperial College
Norfolk Place
W2 1PG
United Kingdom
+44 (0)20 7594 3990

Sponsor type




Funder type


Funder name

The Wellcome Trust (UK) (grant ref: 062258)

Alternative name(s)

Funding Body Type

Funding Body Subtype


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

Results - basic reporting

Publication summary

1. 2003 retrospective review in
2. 2005 preliminary results in
3. 2006 results in
4. 2010 results in

Publication citations

  1. Retrospective review

    Maitland K, Levin M, English M, Mithwani S, Peshu N, Marsh K, Newton CR, Severe P. falciparum malaria in Kenyan children: evidence for hypovolaemia., QJM, 2003, 96, 6, 427-434.

  2. Preliminary results

    Maitland K, Pamba A, English M, Peshu N, Marsh K, Newton C, Levin M, Randomized trial of volume expansion with albumin or saline in children with severe malaria: preliminary evidence of albumin benefit., Clin. Infect. Dis., 2005, 40, 4, 538-545, doi: 10.1086/427505.

  3. Results

    Akech S, Gwer S, Idro R, Fegan G, Eziefula AC, Newton CR, Levin M, Maitland K, Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial., PLoS Clin Trials, 2006, 1, 5, e21, doi: 10.1371/journal.pctr.0010021.

  4. Results

    Akech SO, Jemutai J, Timbwa M, Kivaya E, Boga M, Fegan G, Maitland K, Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria., Crit. Care Med., 2010, 38, 8, 1630-1636, doi: 10.1097/CCM.0b013e3181e81165.

Additional files

Editorial Notes