Clinical trial NCT01653665: Does GM-CSF Restore Neutrophil Phagocytosis in Critical Illness?
Official title: Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Critical Illness
Sepsis
Immuno-suppression
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: Newcastle University
First posted: 2012-07-31
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Fulfil criteria for systemic inflammatory response syndrome on admission to ICU (see appendix 1)
* Has required support of one or more organ systems (invasive ventilation, inotropes or haemofiltration) during current ICU stay
* Survival over next 48 hours deemed most likely outcome by responsible ICU clinician
* Admitted to ICU within last 72 hours
* Neutrophil phagocytic capacity \<50%

Exclusion Criteria:

* Absence/refusal of informed consent
* Current prescription of a colony stimulating factor
* Any history of allergy/adverse reaction to GM-CSF
* Total white cell count \>30x109/litre at time of screening
* Haemoglobin \< 7.5g/dl at the time of screening
* Age \< 18 years
* Pregnancy or lactation
* Known in-born errors of neutrophil metabolism
* Known haematological malignancy and/or known to have \>10% peripheral blood blast cells
* Known aplastic anaemia or pancytopaenia
* Platelet count \<50x109/litre
* Chemotherapy or radiotherapy within the last 24 hours
* Solid organ or bone marrow transplantation
* Use of maintenance immunosuppressive drugs other than maintenance corticosteroids (allowed up to 10mg prednisolone/day or equivalent)
* Known HIV infection
* Active connective tissue disease (e.g. rheumatoid disease, systemic lupus erythematosus) requiring active pharmacological treatment.
* ST-segment elevation myocardial infarction, acute pericarditis (by ECG criteria) or pulmonary embolism (radiographically confirmed) in previous week
* Involvement in any study involving an investigational medicinal product in the previous 30 days

Primary outcomes:
measure: Neutrophil phagocytosis
timeFrame: 2 days after GMCSF/placebo administration
Secondary outcomes:
measure: neutrophil phagocytic capacity on alternate study days
timeFrame: 0 - 9 days
measure: Other measures of neutrophil function
timeFrame: 0-9 days
measure: Monocyte HLA-DR expression
timeFrame: 0-9 days
measure: Serum measures of inflammatory response
timeFrame: 0-9 days
measure: Sequential organ failure assessment (SOFA)
timeFrame: up to end of study participation, a maximum of 30 days for each participant
measure: Length of ICU stay
timeFrame: Up to end of participation in study, a maximum of 30 days
measure: Incidence of ICUAIs (Intensive care unit acquired infection)
timeFrame: Up to end of study participation, a maximum of 30 days for each patients
measure: All cause mortality
timeFrame: 30 days post randomisation
measure: Number of days of mechanical ventilation
timeFrame: Up to end of study participation, a maximum of 30 days
measure: Blood sample analysis
timeFrame: 0-9 days
Other outcomes:
Locations:
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
state: Tyne And Wear
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: Tyne And Wear
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
Study officials:
affiliation: Newcastle University
name: John Simpson
role: PRINCIPAL_INVESTIGATOR
References: