Complement mediated dysfunctional neutrophil phagocytosis in critical illness. MedDRA version: 14.1 Level: PT Classification code 10061314 Term: Neutrophil function disorder System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 16.1 Level: LLT Classification code 10017500 Term: Functional disorders of polymorphonuclear neutrophils System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 14.1 Level: PT Classification code 10061867 Term:
Conditions
Interventions
Trade Name: Leukine
Product Name: Leukine (Sargramostim)
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Sargramostim
CAS Number: 123774-72-1
Other descriptive name:
Sponsors
Newcastle Upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients admitted to intensive care unit within the last 72 hours Fulfill criteria for systemic inflammatory response syndrome (SIRS) Have required exogenous support of one or more organ systems (invasive ventilation, inotropes or haemofiltration) during current ICU stay Survival over next 48 hours considered to be the most likely outcome over this time by the attending clinician at the time of enrollment Neutrophil phagocytic capacity is low (i.e. =65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: Absence/refusal of informed consent Current prescription of a colony stimulating factor Any history of adverse reaction/allergy to GM-CSF Total white cell count > 30x10^9/litre at the time of screening Haemoglobin 10% peripheral blood blast cells Known aplastic anaemia or pancytopaenia Platelet count <50x10^9/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 prednisolone 10mg/day or equivalent) Known human immunodeficiency virus (HIV) infection Active connective tissue disease (eg rheumatoid disease, systemic lupus erythematosus) requiring active pharmacological treatment ST segment elevation myocardial infarction, acute pericarditis (by ECG criteria) or pulmonary embolism (radiologically confirmed) in the previous week Involvement in any study involving an investigational medicinal product in the previous 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Will GM-CSF (a drug used to stimulate white blood cells) be able to restore the ingestion of germs by neutrophils (the most important white blood cells in fighting bacterial and fungal infection) to fight off infection in critically ill patients on intensive care?;Secondary Objective: Will GM-CSF ( a drug used to stimulate white blood cells) have any effect on 1)the function of monocytes (another type of white blood cell involved in fighting infection) 2)the incidence of patients developing secondary infection while in intensive care 3)death rates of patients requiring intensive care 4)length of stay on the intensive care unit 5)the function of patients organs while in intensive care 6)the length of mechanical ventilation of patients on intensive care ;Primary end point(s): The primary outcome is neutrophil phagocytic capacity 2 days after administration of GM-CSF or placebo (as measured by percentage of neutrophils ingesting greater than or equal to 2 zymosan particles ex vivo).;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated after 2 days of commencing GM-CSF or placebo. Several secondary endpoints will also be evaluated. (Where a trained researcher is not available blood may be taken the following day) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Neutrophil phagocytic capacity measured as 'area under the curve' over the study period 2.Sequential neutrophil phagocytic capacity on alternate study days (and days 9 and 10)- to determine sustainability of any observed effects in the primary endpoint. 3.Sequential organ failure score (SOFA) 4.Length of stay in ICU 5.The incidence of ICUAIs (as defined by Hospitals in Europe Link for Infection Control Surveillance (HELICS) criteria) 6.30 day mortality 7.Other assessments of neutrophil function which may include but not be limited to ROS generation, migratory capacity, and apoptotic rate 8.Monocyte HLA-DR expression on alternate study days (and days 8 & 9). 9.Total white cell count 10.Neutrophil, monocyte, eosinophil and lymphocyte counts 11.Safety including full blood count, urea and electrolytes, liver function tests, neutralising antibodies to GM-CSF, recording and reporting of serious adverse events;Timepoint(s) of evaluation of this end point: 1. Day 9 2. **Days 0,2,4,6,8 & 9 3. Days 0-10,20,30 4. Days 0-10,20,30 5. Days 0-10,20,30 6. Day 30 7. **Days 0,2,4,6,8 & 9 8. **Days 0,2,4,6,8 & 9 9. Days 0-9 10.Days 0-9 11.Days 0-9 ** Where a trained researcher is not available blood may be taken the following day | — |
Countries
United Kingdom
Contacts
Public ContactProfessor John Simpson,
Newcastle Upon Tyne Hospitals NHS Foundation Trust
Outcome results
None listed