Sepsis Trials in Critical Care (SepTiC)

Research summary

Design: A 2x2 factorial pragmatic open-label randomised controlled trial,with an embedded randomised double-blind parallel group trial Setting: 60 general ICUs in the UK Target population: Adult patients who are critically ill due to sepsis Inclusion criteria - Adult patients admitted to ICU due to suspected sepsis and expected to stay for at least 48 hours - Receiving intravenous antibiotics for suspected sepsis - Initial early fluid resuscitation complete - Acute organ dysfunction due to infection Additional criteria for GM-CSF subset - Mechanically ventilated - Receiving vasopressors/inotropes - Absolute lymphocyte count <1.2 x109/L on two consecutive days Exclusion criteria - More than 12hours since ICU admission - Previously admitted to ICU due to sepsis on this hospital admission - Not expected to survive 90 days,due to pre-existing chronic disease - Not expected to survive initial resuscitation (24 hours) - Neutropenia due to chemotherapy/malignancy (but not due to sepsis) - A source of infection that will require a prolonged course of antibiotics,>21 days - Additional exclusion criteria for GM-CSF Health Technologies being assessed 1. Rapid PCR-based microbiological diagnostics combined with procalcitonin compared with standard care 2. Conservative fluid therapy with active removal of accumulated fluid (de-resuscitation) compared to standard care 3. GM-CSF (sargramostim) 6μg/kg/day for 7 days compared to placebo Measurement of costs & outcomes Primary: 90-day all-cause mortality (for all interventions) Secondary: - Duration of mechanical ventilation,shock,renal replacement therapy - Length of stay in ICU and hospital - Antibiotic use (defined daily doses per 1000 occupied bed days) - Infection relapse / recurrence or secondary infection requiring further antibiotic treatment - Adverse events and drug reactions (including antibiotic related adverse events) - Health-related Quality of Life (EQ-5D-5L) and cognitive function (MoCA-Blind) at 6 months - 1-year mortality Sample size: 3758 patients in total,allowing for 10% inflation due to the factorial design and 2% loss to follow-up. 1300 patients are required for the high-risk GM-CSF subset. Timeline: After 9 months set-up time,3 years are required for recruitment,based on 2 patients recruited per ICU per month. Allowing for 1 year follow up and 3 months final analysis and reporting,this totals 60 months for the project. Expertise: Our team includes critical care,microbiology and emergency medicine clinicians,trialists,statisticians,health economists,a psychologist and a patient representative. Our team has expertise in sepsis management,antimicrobial resistance,diagnostics,ICU trial design/methodology/analysis,health economics,communication and strong links with patient groups.

Principal Investigator

Dr Graham Barker

Contact us

Email: ICUResearch@ouh.nhs.uk

IRAS number

1005848