Permissive Hyperthermia Through Avoidance of Paracetamol in Sepsis trial (HEAT) study
Severe sepsis is an important cause of serious morbidity and mortality in New Zealand. The adult population incidence of severe sepsis is 0.77 per 1000 population per year with a 28-day mortality of 32.4% and a median hospital stay from the onset of sepsis of 18 days.
Due to the highly lethal nature of the disease and the expense associated with its treatment, the burden of disease and the economic impact of sepsis are considerable and are probably comparable to that of ischaemic heart disease. Any novel intervention which reduced the duration and severity of severe sepsis would result in a major impact on the burden of infectious disease in New Zealand. It would also result in major savings to the health system due to the high cost of intensive care treatment.
The primary objective of this study is to determine if a permissive temperature strategy increases the number of ‘alive ICU-free days’ to day 28 compared with a usual care strategy of administration of paracetamol for fever to critically ill patients with known or suspected infection.
The study will establish whether a definitive phase III trial is safe, feasible and justifiable, and will provide essential information on the cost and likely sample size for such a trial.
The HEAT trial is a prospective, phase 2b, multi-centre, blinded, parallel-groups randomised placebo-controlled trial, designed to determine the safety, efficacy and feasibility of a permissive temperature strategy compared to a paracetamol-based strategy in critically ill patients with known or suspected infection.
Approximately 22 sites from Australia and New Zealand will enrol 700 patients to the HEAT study. Intensive care patients that meet study inclusion criteria will be randomly assigned to either the blinded paracetamol or the placebo group in a 1:1 ratio. After randomisation, the patient will receive either 1 gram of paracetamol or placebo (5% Dextrose) six hourly as per study protocol. Patients will be followed up at days 28 and 90. This study has approval for delayed consent as appropriate.
The study began recruiting in February 2013 and is in the final stages of recruitment, set to be completed in September 2014.