Sepsis Trials in Critical Care
Sepsis
Intervention 1:- Diagnostic Trial Research Question:- Do rapid PCR-based microbiological diagnostics combined with procalcitonin improve outcomes and antibiotic stewardship compared to standard care in patients admitted to intensive care (ICU) with sepsis? Intervention Arms:- PCR test and procalcitonin result or Standard of Care If randomised to intervention a PCR test and Procalcitonin check will be completed. A blood sample will be taken after randomisation for rapid PCR-based pathogen testing, which will be sent to the study laboratory. Procalcitonin (PCT) will be measured on the day of inclusion and the next calendar day. If randomised to standard of care patients will be prescribed antibiotics according to the local antibiotic prescribing guidelines and using standard microbiology sampling, culture and sensitivity testing. Intervention 2:- Fluid Trial Research Question:- Does conservative fluid therapy with active removal of accumulated fluid (de-resuscitation) improve outcomes compared to standard care in patients admitted to ICU with sepsis? Intervention Arms:- Conservative fluid therapy with de-resuscitation or Standard of Core If randomised to intervention, conservative fluid strategy will be followed as soon as possible after randomisation. From Day 2 – 5 patients will be assessed for cardiovascular stability. If cardiovascularly stable and there are signs of fluid overload, deresuscitation will be given. Deresuscitation will consist of combination diuretic therapy . If randomised to standard care will be prescribed fluids according to usual care, at the discretion of the treating clinicians. Intervention 3:- GM-CSF Trial Research Question:- Does GM-CSF compared to placebo improve outcomes in a high-risk subset of patients admitted to ICU with sepsis? If randomised to intervention, GM-CSF 250-500 µg will be given subcutaneously once a day for up to 8 days. If randomised to standard care a matching placebo will be given.
1. Adults (≥16 years of age) admitted to ICU due to suspected sepsis and expected to stay for at least two calendar days (i.e. expected to still to be in ICU the day after tomorrow). 2. Receiving intravenous antibiotics for suspected sepsis 3. According to local clinical judgement, patient has received adequate initial early fluid resuscitation The following inclusion are for intervention 3 only (can be after initial trial entry): 1. Intubated and mechanically ventilated and expected to continue for another 24 hours 2. Or requiring two organ support (i.e. vasopressors or renal replacement therapy) 3. An absolute lymphocyte count < 1.2 x109 /L on two consecutive calendar days at least 12 hours apart, with no values >1.2 x10^9 /L in between.
Current key exclusion criteria as of 16/07/2026: 1. More than 24 hours since ICU admission (this does NOT apply for trial 3, GM-CSF). Note: As early intervention in sepsis is important, the aim should be to enrol eligible patients as soon after ICU admission as is practically possible. 2. Previously admitted to ICU due to sepsis on this hospital admission 3. Not expected to survive initial resuscitation (24 hours) 4. Neutropaenia (<0.5 neutrophils x109 /L) due to chemotherapy/malignancy (but not due to sepsis) 5. Being treated for infective endocarditis, osteomyelitis, hepatic or cerebral abscess, tuberculosis (e.g. infective endocarditis, osteomyelitis, hepatic or cerebral abscess, tuberculosis) 6. Diabetic ketoacidosis (DKA) or hyperglycaemic hyperosmolar state (HHS) 7. Within 21 days of a spontaneous subarachnoid haemorrhage 8. Diabetes Insipidus 9. Weight <40Kg The following additional criteria relate to intervention 3 only: 1. More than 120 hours since ICU admission 2. Already receiving G-CSF or GM-CSF 3. A total white blood cell count >50 x10^9 /L 4. Allergy or previous adverse reaction to GM-CSF 5. Known to be pregnant or breastfeeding 6. Known recent (required treatment within the last 5 years) haematological malignancy 7. Solid organ or bone marrow transplantation 8. Patient weight >125kg 9. Known anaphylaxis to GM-CSF or yeast-derived products Previous key exclusion criteria: 1. More than 24 hours since ICU admission (this does NOT apply for trial 3, GM-CSF). Note: As early intervention in sepsis is important, the aim should be to enrol eligible patients as soon after ICU admission as is practically possible. 2. Previously admitted to ICU due to sepsis on this hospital admission 3. Not expected to survive 90 days, due to pre-existing chronic (end-stage) disease 4. Not expected to survive initial resuscitation (24 hours) 5. Neutropaenia (<0.5 neutrophils x109 /L) due to chemotherapy/malignancy (but not due to sepsis) 6. A source of infection that wil