Mild induced hypothermia for severe falciparum malaria

ISRCTN	ISRCTN34508212
DOI	https://doi.org/10.1186/ISRCTN34508212
Protocol serial number	V1.3
Sponsor	University of Oxford (UK)
Funder	University of Oxford (UK)

Submission date: 19/06/2013
Registration date: 23/10/2013
Last edited: 06/08/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

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?
May 2014 to May 2015

Who is funding the study?
Oxford University (UK)

Who is the main contact?
Dr Brian Angus
brian.angus@ndm.ox.ac.uk

Contact information

Dr Brian Angus
Scientific

Rm7400, L7 The John Radcliffe Hospital
Headington
Oxford
OX3 9DU
United Kingdom

Email	brian.angus@ndm.ox.ac.uk

Study information

Primary study design	Interventional
Study design	Non-randomised pilot study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	A pilot study of mild induced hypothermia for severe falciparum malaria
Study objectives	Mild induced hypothermia is safe and efficacious in severe falciparum malaria.
Ethics approval(s)	The Oxford Tropical Research Ethics Committee (OxTREC) 06-12
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	01/05/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	10
Key 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
Key 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
Date of first enrolment	01/05/2014
Date of final enrolment	01/05/2015

Locations

Countries of recruitment

United Kingdom
England
Bangladesh

Study participating centre

The John Radcliffe Hospital

Oxford
OX3 9DU
United Kingdom

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?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

06/08/2020: No publications found.
09/08/2017: No publications found, verifying study status with principal investigator.