Does GM-CSF Restore Neutrophil Phagocytosis in Critical Illness? (GMCSF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor:
Collaborators:
Medical Research Council
Newcastle University
Information provided by (Responsible Party):
Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01653665
First received: July 16, 2012
Last updated: May 20, 2014
Last verified: June 2013
  Purpose

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 Intervention Phase
Critical Illness
Sepsis
Immuno-suppression
Drug: Leukine
Drug: Normal Saline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?

Resource links provided by NLM:


Further study details as provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Primary Outcome Measures:
  • Neutrophil phagocytosis [ Time Frame: 2 days after GMCSF/placebo administration ] [ Designated as safety issue: No ]
    neutrophil phagocytic capacity will be measured as the percentage of neutrophils ingesting 2 or more zymosan particles ex vivo


Secondary Outcome Measures:
  • neutrophil phagocytic capacity on alternate study days [ Time Frame: 0 - 9 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    May include but not limited to: ROS generation, migration capacity and apoptotic rate

  • Monocyte HLA-DR expression [ Time Frame: 0-9 days ] [ Designated as safety issue: No ]
    Alternate days by flow-cytometry

  • Serum measures of inflammatory response [ Time Frame: 0-9 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Length of ICU stay [ Time Frame: Up to end of participation in study, a maximum of 30 days ] [ Designated as safety issue: No ]
  • Incidence of ICUAIs (Intensive care unit acquired infection) [ Time Frame: Up to end of study participation, a maximum of 30 days for each patients ] [ Designated as safety issue: No ]
    As defined by hospitals in europe link for infection control surveillance (HELICS)

  • All cause mortality [ Time Frame: 30 days post randomisation ] [ Designated as safety issue: No ]
  • Number of days of mechanical ventilation [ Time Frame: Up to end of study participation, a maximum of 30 days ] [ Designated as safety issue: No ]
  • Blood sample analysis [ Time Frame: 0-9 days ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 70
Study Start Date: August 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Leukine
Daily subcutaneous injection of either 3 or 6 micrograms per kilo per day, for either 4 or 7 days.
Other Names:
  • Sargramostim
  • GM-CSF
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653665

Contacts
Contact: John Simpson 0191 222 7770 j.simpson@ncl.ac.uk
Contact: Jennie Parker 0191 2085825 jennie.parker@ncl.ac.uk

Locations
United Kingdom
Queen Elizabeth Hospital Recruiting
Gateshead, Tyne and Wear, United Kingdom, NE9 6SX
Contact: Vanessa Linnett       vaness.linnett@ghnt.nhs.uk   
Principal Investigator: Vanessa Linnett         
Freeman Hospital Recruiting
Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
Contact: Simon Baudouin    0191 233 6161 ext 24912    s.v.baudouin@ncl.ac.uk   
Contact: Tom Hellyer    0191 208 7770    thomas.hellyer@ncl.ac.uk   
Principal Investigator: Simon Baudouin         
Royal Victoria Infirmary Recruiting
Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
Contact: Simon Baudouin    0191 233 6161 ext 24912    s.v.baudouin@ncl.ac.uk   
Contact: Tom Hellyer    0191 208 7770    thomas.hellyer@ncl.ac.uk   
Principal Investigator: Simon Baudouin         
Sunderland Royal Hospital Recruiting
Sunderland, United Kingdom
Contact: Aly Roy    0191 565 6256    alyroy@mac.com   
Principal Investigator: Alistair Roy         
Sponsors and Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Medical Research Council
Newcastle University
Investigators
Principal Investigator: John Simpson Newcastle University
  More Information

No publications provided

Responsible Party: Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01653665     History of Changes
Other Study ID Numbers: AJSEB001, G1100233, 2011-005815-10, ISRCTN95325384
Study First Received: July 16, 2012
Last Updated: May 20, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Critical Illness
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2014