CompletedPhase 2ACTRN12616001285448

Randomised Evaluation of Active Control of Temperature vs. Ordinary temperature management in mechanically ventilated adults in ICU with fever.

A multi-centre, phase II, randomized, open label, clinical trial comparing combined prophylactic intravenous paracetamol and early targeted physical cooling for fever with standard temperature management in mechanically ventilated adults without acute brain pathologies who are expected to be ventilated beyond the day after randomisation.

Sponsor

Medical Research Institute of New Zealand

Enrollment

184 participants

Start Date

Nov 25, 2016

Study Type

Interventional

Conditions

Fever

Summary

Background: Intensive care doctors make decisions about prevention and treatment of fever every day but their decisions are currently made on the basis of very weak evidence. Although ICU patients often have limited physiological reserves so that their tolerance of the demands on the body created by fever may be limited, clinicians are generally tolerant of relatively high body temperatures in the absence of acute brain pathologies. Study question: Among adults in ICU without acute brain pathologies who are expected to life support (a breathing machine) beyond the day after randomisation, does systematic control of body temperature using regular IV paracetamol combined with physical cooling to treat fever alter mean body temperature compared to standard temperature management? Why this study is being conducted: Understanding whether or not an active approach to prevention and treatment of fever results in a lower mean body temperature than a standard care approach is a necessary prerequisite to evaluating the active approach in a phase 3 clinical trial. Obtaining high level evidence to inform clinical practice in relation to temperature management in patients without acute brain pathologies requiring invasive mechanical ventilation is a high priority because fever is common problem and the best approach to managing fever is uncertain.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria3

Patients requiring invasive mechanical ventilation in the ICU and expected to be receiving mechanical ventilation beyond the day after randomisation.
Fever (body temperature 37.8 degrees Celsius or more) in the previous 12 hours.
Deeply sedated with no response to voice

Exclusion Criteria7

Acute brain pathologies (traumatic brain injury, intracerebral haemorrhage, subarachnoid haemorrhage, or ischaemic stroke).
Confirmed or suspected hypoxic ischaemic encephalopathy (includes all patients who have had a recent cardiac arrest where there is clinical concern about possible brain damage as a result of the cardiac arrest).
Death is deemed to be inevitable as a result of the current acute illness and either the treating clinician, the patient, or the substitute decision maker are not committed to full active treatment.
Patients admitted to the intensive care unit with greater than or equal to 20% total body surface area burns.
Life expectancy of less than 90 days due to an underlying medical condition.
Fulfilled all other eligibility criteria >24 hours ago but was not enrolled in the study.
Previously enrolled in the REACTOR study.

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Interventions

Where clinically appropriate, administer regular IV paracetamol 1 gm 6 hourly as ‘fever prophylaxis’. If the patient is deeply sedated with no response to voice, target a body temperature of no greater than 36.5-37 degrees Celsius using simple cooling measures (removal of clothing and sheets, using a sponge or wet towel, using a fan) plus a physical cooling device if necessary. Physical cooling devices are any device at the study site that the treating clinician considers appropriate such as cooling blankets, cooling pads and cooling helmets. Shivering should be aggressively treated where possible using the following hierarchy of treatments: 1. Administration of an opioid bolus 2. Increasing of sedation 3. Administration of a bolus of neuromuscular paralysis Decisions regarding choice of drugs, doses, frequency, and duration of administration will be at the discretion of the treating clinician. Protocol-driven temperature control measures including IV paracetamol should be ceased at day 28 or ICU discharge (whichever is sooner). Physical cooling can be ceased to allow the patient to be desedated at any time at the discretion of the treating clinician but should be recommenced if further deep sedation is needed and body temperature is not within the target range of 36.5-37 degrees Celsius. If treatments to control shivering are clinically inappropriate or shivering cannot be controlled then physical cooling should be ceased.