Critical IllnessPhase 1/2GMCSFNCT01653665
Does GM-CSF Restore Neutrophil Phagocytosis in Critical Illness?
A Phase 1/2 study testing Leukine and Normal Saline in people with Critical Illness and Sepsis, run by Newcastle-upon-Tyne Hospitals NHS Trust at 4 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Sepsis, Immuno-suppression
- What is being tested?
- Leukine and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- Aug 2012to Feb 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Queen Elizabeth Hospital
Gateshead, Tyne and Wear, NE9 6SX
Royal Victoria Infirmary
Newcastle upon Tyne, Tyne and Wear, NE1 4LP
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
Sunderland Royal Hospital
Sunderland
About this study
Official title: Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?
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
Read more
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.
- Conditions
- Critical Illness, Sepsis, Immuno-suppression
- Being tested
- Leukine, Normal Saline
- Medical subject headings
- Critical Illness, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeukineDrug
Also called Sargramostim, GM-CSF
Daily subcutaneous injection of either 3 or 6 micrograms per kilo per day, for either 4 or 7 days.
Normal SalineDrug
Also called placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| Leukine (Sargramostim, GM-CSF) | Active comparator | 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. Receives: Drug: Leukine |
| Placebo (normal saline) | Placebo comparator | 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 Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutrophil phagocytosis
neutrophil phagocytic capacity will be measured as the percentage of neutrophils ingesting 2 or more zymosan particles ex vivo
Measured: 2 days after GMCSF/placebo administration
Secondary outcomes (10)
neutrophil phagocytic capacity on alternate study days
Measured on alternate days and also as 'area under the curve' over the study period
Measured: 0 - 9 days
Other measures of neutrophil function
May include but not limited to: ROS generation, migration capacity and apoptotic rate
Measured: 0-9 days
Monocyte HLA-DR expression
Alternate days by flow-cytometry
Measured: 0-9 days
Serum measures of inflammatory response
May include but not limited to: cytokine levels
Measured: 0-9 days
Sequential organ failure assessment (SOFA)
Measured: up to end of study participation, a maximum of 30 days for each participant
Length of ICU stay
Measured: Up to end of participation in study, a maximum of 30 days
Incidence of ICUAIs (Intensive care unit acquired infection)
As defined by hospitals in europe link for infection control surveillance (HELICS)
Measured: Up to end of study participation, a maximum of 30 days for each patients
All cause mortality
Measured: 30 days post randomisation
Number of days of mechanical ventilation
Measured: Up to end of study participation, a maximum of 30 days
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
Measured: 0-9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2012 (estimated)
- Study startAug 2012
- Primary completionJan 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, Newcastle University
- Responsible party
- Sponsor
- Investigators
- John Simpson, Principal investigator, Newcastle University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01653665
- Sponsor's protocol ID
- AJSEB001
- Other IDs
- G1100233, 2011-005815-10, ISRCTN95325384
- Acronym
- GMCSF
- Status last verified
- Feb 2018
- First submitted
- 16 Jul 2012
- Last updated
- 13 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does GM-CSF Restore Effective Neutrophil Function in Critically Ill Patients?
- ClinicalTrials.gov ID
- NCT01653665
- Acronym / sponsor ID
- GMCSF / AJSEB001
- Conditions
- Critical Illness, Sepsis, Immuno-suppression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Medical Research Council, Newcastle University
- Study start
- Aug 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 31 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Leukine (Sargramostim, GM-CSF) | Active comparator | Drug: LeukineParticipants 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. |
| Placebo (normal saline) | Placebo comparator | Drug: Normal SalineParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeukineAlso: Sargramostim, GM-CSFDaily subcutaneous injection of either 3 or 6 micrograms per kilo per day, for either 4 or 7 days. | Drug | Leukine (Sargramostim, GM-CSF) |
| Normal SalineAlso: placeboPatients in the randomised controlled trial may receive this placebo as a single daily subcutaneous injection. The volume will match that of the active drug. | Drug | Placebo (normal saline) |
Primary outcome
Neutrophil phagocytosis
Time frame: 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
10 secondary outcomes
neutrophil phagocytic capacity on alternate study days
Time frame: 0 - 9 days
Other measures of neutrophil function
Time frame: 0-9 days
Monocyte HLA-DR expression
Time frame: 0-9 days
Serum measures of inflammatory response
Time frame: 0-9 days
Sequential organ failure assessment (SOFA)
Time frame: up to end of study participation, a maximum of 30 days for each participant
Length of ICU stay
Time frame: Up to end of participation in study, a maximum of 30 days
Incidence of ICUAIs (Intensive care unit acquired infection)
Time frame: Up to end of study participation, a maximum of 30 days for each patients
All cause mortality
Time frame: 30 days post randomisation
Number of days of mechanical ventilation
Time frame: Up to end of study participation, a maximum of 30 days
Blood sample analysis
Time frame: 0-9 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Simpson principal investigator
Newcastle University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Leukine and Normal Saline in people with Critical Illness and Sepsis, run by Newcastle-upon-Tyne Hospitals NHS Trust at 4 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neutrophil phagocytosis (time frame: 2 days after GMCSF/placebo administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.