Does GM-CSF Restore Neutrophil Phagocytosis in Critical Illness? (GMCSF)
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|ClinicalTrials.gov Identifier: NCT01653665|
Recruitment Status : Completed
First Posted : July 31, 2012
Last Update Posted : February 13, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Critical Illness Sepsis Immuno-suppression||Drug: Leukine Drug: Normal Saline||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?|
|Study Start Date :||August 2012|
|Actual Primary Completion Date :||January 2015|
|Actual Study Completion Date :||February 2015|
Active Comparator: Leukine (Sargramostim, GM-CSF)
Participants in dose finding study will receive either 3 or 6 micrograms per kilo per day as a daily subcutaneous injection for either 4 or 7 days. Within the Randomised controlled trial, participants will receive the dose as chosen following the dose finding study.
Daily subcutaneous injection of either 3 or 6 micrograms per kilo per day, for either 4 or 7 days.
Placebo Comparator: Placebo (normal saline)
Participants in the randomised controlled trial may be randomised to receive a daily subcutaneous injection of normal saline (placebo) for 4 or 7 days as decided following the results of the dose finding study
Drug: Normal Saline
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.
Other Name: placebo
- Neutrophil phagocytosis [ Time Frame: 2 days after GMCSF/placebo administration ]neutrophil phagocytic capacity will be measured as the percentage of neutrophils ingesting 2 or more zymosan particles ex vivo
- neutrophil phagocytic capacity on alternate study days [ Time Frame: 0 - 9 days ]Measured on alternate days and also as 'area under the curve' over the study period
- Other measures of neutrophil function [ Time Frame: 0-9 days ]May include but not limited to: ROS generation, migration capacity and apoptotic rate
- Monocyte HLA-DR expression [ Time Frame: 0-9 days ]Alternate days by flow-cytometry
- Serum measures of inflammatory response [ Time Frame: 0-9 days ]May include but not limited to: cytokine levels
- 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) [ Time Frame: Up to end of study participation, a maximum of 30 days for each patients ]As defined by hospitals in europe link for infection control surveillance (HELICS)
- 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 [ Time Frame: 0-9 days ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01653665
|Queen Elizabeth Hospital|
|Gateshead, Tyne And Wear, United Kingdom, NE9 6SX|
|Royal Victoria Infirmary|
|Newcastle upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP|
|Newcastle upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN|
|Sunderland Royal Hospital|
|Sunderland, United Kingdom|
|Principal Investigator:||John Simpson||Newcastle University|