Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 4
- 主要终点
- Neutrophil phagocytosis
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Leukine (Drug)
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
干预措施: Normal Saline (Drug)
结局指标
主要结局
Neutrophil phagocytosis
时间窗: 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
次要结局
- neutrophil phagocytic capacity on alternate study days(0 - 9 days)
- Monocyte HLA-DR expression(0-9 days)
- Serum measures of inflammatory response(0-9 days)
- Other measures of neutrophil function(0-9 days)
- Length of ICU stay(Up to end of participation in study, a maximum of 30 days)
- Incidence of ICUAIs (Intensive care unit acquired infection)(Up to end of study participation, a maximum of 30 days for each patients)
- All cause mortality(30 days post randomisation)
- Number of days of mechanical ventilation(Up to end of study participation, a maximum of 30 days)
- Sequential organ failure assessment (SOFA)(up to end of study participation, a maximum of 30 days for each participant)
- Blood sample analysis(0-9 days)