ISRCTN - ISRCTN34508212: Mild induced hypothermia for severe falciparum malaria

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

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

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 study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details 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 measure

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 (if study stopped)

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

The John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor type

University/education

Website

Funders

Funder type