Does GM-CSF Restore Neutrophil Phagocytosis in Critical Illness?

Sepsis Clinical Trial

— GMCSF  

Official title:

Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01653665
• Other study ID #: AJSEB001
• Secondary ID: G11002332011-005
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 16, 2012
• Last updated: February 12, 2018
• Start date: August 2012
• Est. completion date: February 2015

Study information

• Verified date: February 2018
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Immuno-suppression
• Sepsis

Intervention

Drug:
• Leukine
Daily subcutaneous injection of either 3 or 6 micrograms per kilo per day, for either 4 or 7 days.
• 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.

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth Hospital	Gateshead	Tyne And Wear
United Kingdom	Freeman Hospital	Newcastle upon Tyne	Tyne And Wear
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne	Tyne And Wear
United Kingdom	Sunderland Royal Hospital	Sunderland

Sponsors (3)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust	Medical Research Council, Newcastle University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neutrophil phagocytosis	neutrophil phagocytic capacity will be measured as the percentage of neutrophils ingesting 2 or more zymosan particles ex vivo	2 days after GMCSF/placebo administration
Secondary	neutrophil phagocytic capacity on alternate study days	Measured on alternate days and also as 'area under the curve' over the study period	0 - 9 days
Secondary	Other measures of neutrophil function	May include but not limited to: ROS generation, migration capacity and apoptotic rate	0-9 days
Secondary	Monocyte HLA-DR expression	Alternate days by flow-cytometry	0-9 days
Secondary	Serum measures of inflammatory response	May include but not limited to: cytokine levels	0-9 days
Secondary	Sequential organ failure assessment (SOFA)		up to end of study participation, a maximum of 30 days for each participant
Secondary	Length of ICU stay		Up to end of participation in study, a maximum of 30 days
Secondary	Incidence of ICUAIs (Intensive care unit acquired infection)	As defined by hospitals in europe link for infection control surveillance (HELICS)	Up to end of study participation, a maximum of 30 days for each patients
Secondary	All cause mortality		30 days post randomisation
Secondary	Number of days of mechanical ventilation		Up to end of study participation, a maximum of 30 days
Secondary	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	0-9 days