Despite the introduction of multiple preventative measures rates of hospital acquired infection in the intensive care unit remain high. New approaches to tackling this problem are required. The neutrophil (a type of white blood cell) is the key cell fighting bacterial and fungal infection in the body. This research group has already shown that the majority of patients on intensive care have neutrophils which don't ingest germs effectively and are therefore less able to fight infection. These patients, whose white blood cells don't work properly, are much more likely to develop a second infection whilst in hospital (hospital acquired infection). Previous work done by this group has shown that by adding a drug called granulocyte macrophagecolony stimulating factor (GM-CSF) to a sample of blood from these patients in the lab, it is possible to restore the ability of the white blood cells to ingest bacteria and fight infection. This study will test whether it is possible to restore the capacity of patients' white blood cells to eat germs by giving them GM-CSF as an injection while they are on intensive care. The study will involve identifying adult patients on intensive care whose white blood cells don't work properly in this way. Patients taking part in the study will receive an injection, under the skin, of either the drug, GM-CSF, or a solution which will have no effect (placebo). The investigators will compare whether those patients who have received the GM-CSF injection have an improvement in the function of the white blood cells compared to those who don't. As well as looking at the function of the white blood cells the investigators will also study whether there is a difference in the rates of infection picked up in hospital between the two groups. This study is funded by the Medical Research Council.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
64
Daily subcutaneous injection of either 3 or 6 micrograms per kilo per day, for either 4 or 7 days.
Patients in the randomised controlled trial may receive this placebo as a single daily subcutaneous injection. The volume will match that of the active drug.
Queen Elizabeth Hospital
Gateshead, Tyne and Wear, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, Tyne and Wear, United Kingdom
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, United Kingdom
Sunderland Royal Hospital
Sunderland, United Kingdom
Neutrophil phagocytosis
neutrophil phagocytic capacity will be measured as the percentage of neutrophils ingesting 2 or more zymosan particles ex vivo
Time frame: 2 days after GMCSF/placebo administration
neutrophil phagocytic capacity on alternate study days
Measured on alternate days and also as 'area under the curve' over the study period
Time frame: 0 - 9 days
Other measures of neutrophil function
May include but not limited to: ROS generation, migration capacity and apoptotic rate
Time frame: 0-9 days
Monocyte HLA-DR expression
Alternate days by flow-cytometry
Time frame: 0-9 days
Serum measures of inflammatory response
May include but not limited to: cytokine levels
Time frame: 0-9 days
Sequential organ failure assessment (SOFA)
Time frame: up to end of study participation, a maximum of 30 days for each participant
Length of ICU stay
Time frame: Up to end of participation in study, a maximum of 30 days
Incidence of ICUAIs (Intensive care unit acquired infection)
As defined by hospitals in europe link for infection control surveillance (HELICS)
Time frame: Up to end of study participation, a maximum of 30 days for each patients
All cause mortality
Time frame: 30 days post randomisation
Number of days of mechanical ventilation
Time frame: Up to end of study participation, a maximum of 30 days
Blood sample analysis
To measure safety of study medication from blood samples, which will include measures of Full blood count, white cell count (including differential), U\&Es and LFTs, development of neutralising antibodies to GMCSF
Time frame: 0-9 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.