Plain English Summary
Background and study aims
Mild hypothermia (when body temperature drops below 35°C) has been shown to be protective in many situations in intensive care and this study aims to find out whether it could help patients with severe and cerebral malaria. This is a pilot (small scale) study.
Who can participate?
Patients admitted to intensive care with severe malaria can participate in this study.
What does the study involve?
All patients are cooled to between 32 and 34°C using a cooled salt solution injected through their veins, in addition to standard treatment.
What are the possible benefits and risks of participating?
This technique may reduce death or brain damage from severe malaria.
Where is the study run from?
This study is run from University College Hospital, London, UK and Chittagong Medical College, Chittagong, Bangladesh.
When is the study starting and how long is it expected to run for?
The study will start in May 2014 and run for one year.
Who is funding the study?
The study is funded by Oxford University, UK.
Who is the main contact?
Dr Brian Angus
brian.angus@ndm.ox.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Brian Angus
ORCID ID
Contact details
Rm7400
L7 The John Radcliffe Hospital
Headington
Oxford
OX3 9DU
United Kingdom
brian.angus@ndm.ox.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
V1.3
Study information
Scientific title
A pilot study of mild induced hypothermia for severe falciparum malaria
Acronym
Study hypothesis
Mild induced hypothermia is safe and efficacious in severe falciparum malaria.
Ethics approval
The Oxford Tropical Research Ethics Committee (OxTREC) 06-12
Study design
Non-randomised pilot study
Primary study design
Interventional
Secondary study design
Non 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
Malaria
Intervention
All patients will receive mild induced hypothermia along with the standard treatment. Patients will be cooled using cold intravenous saline and external cooling blankets.
Patients will be followed up until discharge from the hospital.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
1. In-hospital mortality
2. 30 day mortality
3. Neurological outcome at day 30
4. Safety
Primary endpoints will be mortality and neurological state at baseline and discharge from hospital
Secondary outcome measures
1. Parasite clearance time
2. Clinical and biochemical measures (see below).
3. Biochemical and hemodynamic measures at the start and completion of therapy will also be compared
4. Area under the curve for microvascular reactivity by reactive hyperemia-peripheral artery tonometry (RH-PAT) [0-25 hrs]
5. Endothelial function [near‐infrared reflectance spectroscopy (NIRS) and RH-PAT]
6. Lactate clearance
7. Improvement in microvascular obstruction [Orthogonal Polarization Spectral (OPS) imaging]
8. Change in tissue oxygen consumption (measured by NIRS occlusion phase)
9. Change in NO production
10. Change in red cell deformability
11. Changes in CSF markers of neuronal and axonal damage and astroglial activation
Overall trial start date
01/05/2014
Overall trial end date
01/05/2015
Reason abandoned
Eligibility
Participant inclusion criteria
1. Age 16-60 years
2. Informed consent obtained (plus parental/guardian assent if 16 or 17 years old)
3. Time of commencement of artesunate ≤18 hrs before therapy
4. Any level of Plasmodium falciparum parasitemia, and one or more of the following criteria:
4.1. Acute renal failure (creatinine >265umol/L)
4.2. Hyperbilirubinemia (total bilirubin >50 umol/L) with either renal impairment (creatinine >130umol/L) or parasitemia of >100,000 parasites/uL
4.3. Blackwater fever
4.4. Hyperparasitemia (>10% parasitised red cells)
4.5. Cerebral malaria (Glasgow coma score <11)
4.6. Hypoglycemia
4.7. Respiratory distress (RR >32)
4.8. Venous bicarbonate 12-15 meq/L (pilot phase) or 8-15 meq/L
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
10
Participant exclusion criteria
1. Pregnancy or lactation
2. Diabetes
3. Serious pre-existing disease (cardiac, hepatic, kidney)
4. History of contraindications to hypothermia (Raynauds disease, Cryoglobulinemia, Sickle Cell disease, serum cold agglutinins, Buergers disease)
5. Bleeding disorders (e.g., hemophilia)
6. An intranasal obstruction or known skull base fracture
Recruitment start date
01/05/2014
Recruitment end date
01/05/2015
Locations
Countries of recruitment
Bangladesh, United Kingdom
Trial participating centre
Rm7400, L7 The John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
Centre for Tropical Medicine
Churchill Hospital
Headington
Oxford
OX9 9LJ
United Kingdom
paul.hogben@ndm.ox.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
University of Oxford (UK)
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
Results - basic reporting
Publication summary