A study comparing granulocyte macrophage-colony stimulating factor (GM-CSF), vaccination and placebo in patients who suffer from immune depression after resection of either pancreas or oesophagus

ISRCTN	ISRCTN27114642
DOI	https://doi.org/10.1186/ISRCTN27114642
Protocol serial number	N/A
Sponsor	Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
Funder	Charité Universitätsmedizin Berlin

Submission date: 05/12/2008
Registration date: 27/02/2009
Last edited: 08/12/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Claudia Spies
Scientific

Augustenburger Platz 1
Berlin
13353
Germany

Phone	+49 (0)30 450 551001
Email	claudia.spies@charite.de

Study information

Primary study design	Interventional
Study design	Prospective randomised double-blinded double-dummy placebo-controlled monocentre pilot study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Influence of post-operative influenza vaccination versus granulocyte macrophage-colony stimulating factor (GM-CSF) in immune-compromised patients undergoing pancreatic or oesophageal resection on the course of immunosuppression and the post-operative infection rate: a prospective, randomised, double-blinded, double-dummy, placebo-controlled, monocentre pilot study
Study acronym	ART VI
Study objectives	The post-operative vaccination or the post-operative treatment with granulocyte macrophage-colony stimulating factor (GM-CSF) produces a higher sufficiency of immune reactivity shown through a normalisation of monocyte human leukocyte antigen-DR (HLA-DR) expression while avoiding immune paralysis in patients suffering from severe immune suppression. On 22/10/10 this record was updated to include an extended overall trial end date, from 31/3/2010 to 31/03/2011, due to the yearly unavailability of study vaccine for several months. The secondary outcomes have also been updated and more details may be found in the relevant field with the above update date. On 09/06/2015 the following changes were made to the trial record: 1. The overall trial start date was changed from 26/10/2008 to 13/05/2008. 2. The overall trial end date was changed from 31/03/2011 to 16/04/2011. 3. The target number of participants was changed from 60 to 63.
Ethics approval(s)	The local ethics committee (Ethics board committee Berlin, Landesamt fur Gesundheit und Soziales [LaGeSo], Berlin) was informed throughout and gave permission for the performance of this clinical trial on the 01/09/2008 (ref : ZS EK 15 287/08)
Health condition(s) or problem(s) studied	Post-operative immunological stimulation in severe immune suppression
Intervention	In this study the potential of post-operative immunological stimulation in patients with immune suppression is compared to placebo: 1. 0.5 ml Mutagrip® 2008/2009 2. 250 µg/m^2 body surface Sargramostim 3. Physiological saline Duration of the treatment: minimal 24 hours, maximum 72 hours Frequency: daily subcutaneous injection and daily 24 hour perfusion for a maximum of 3 days Follow up: 9 post-operative days as well as safety
Intervention type	Biological/Vaccine
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	HLA-DR expression of monocytes on the first 5 post-operative days
Key secondary outcome measure(s)	Current information as of 22/10/10: 1. For all 60 study patients: 1.1. Post-operative infection rate and infection days on the first 9 post-operative days 1.2. Post-operative incidence of delirium and delirium days (CAM-ICU, NuDesc, DDS) on the first 9 post-operative days 1.3. Ventilation time, intensive care unit (ICU) stay, length of stay, APACHE II score, SAPS II score, SOFA score, TISS-28 score (ventilation time and scores on the first 9 post-operative days) 2. For the first 33 study patients: 2.1. Cytokines in serum, Th1/ Th2-ratio, Th17/ Treg-ratio, further parameters of immune function on the first 5 post-operative days 2.2. Quantitative expression of transcription factors (T-bet, Eomesodermin, Gata-3, Foxp3, ROR-gamma t, PU.1, STAT-1, STAT-3, STAT-5, NF kappa B) and proteins (SOCS-3, SOCS-1, SOCS-5, TGF-beta, IL-17, IL-6, IL-10, IFN-?, TNF-a, IL-23, IL-10) as well as the synthesis of the corresponding effector proteins on the first 5 post-operative days Initial information at time of registration: 1. Cytokines in serum, Th1/ Th2-ratio, Th17/ Treg-ratio, further parameters of immune function on the first 5 post-operative days 2. Quantitative expression of transcription factors (T-bet, Eomesodermin, Gata-3, Foxp3, ROR-gamma t, PU.1, STAT-1, STAT-3, STAT-5, NF kappa B) and proteins (SOCS-3, SOCS-1, SOCS-5, TGF-beta, IL-17, IL-6, IL-10, IFN-?, TNF-a, IL-23, IL-10) as well as the synthesis of the corresponding effector proteins on the first 5 post-operative days 3. Post-operative infection rate on the first 9 post-operative days 4. Post-operative incidence of delir (CAM-ICU, NuDesc, DDS) on the first 9 post-operative days 5. Ventilation time, intensive care unit (ICU) stay, length of stay, APACHE II score, SAPS II score, SOFA score, TISS-28 score (ventilation time and scores on the first 9 post-operative days)
Completion date	16/04/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	63
Key inclusion criteria	1. Tumour resection of the upper aero-digestive tract 2. Informed consent 3. Adulthood (aged greater than or equal to 18 years, either sex) 4. Negative pregnancy test 5. Highly effective contraception in premenopausal women 6. No participation in any other pharmaceutical study during the course of the study 7. Monocyte HLA-DR expression below 10.000 antigens/surface on the first post-operative day
Key exclusion criteria	1. Lack of willingness to accept the storage and transfer of pseudonymous data 2. Incapacitation 3. Staff member of the Charité Berlin 4. Pregnancy 5. Lactation 6. Congenital or acquired blood disorder 7. Chemotherapy or radiotherapy within the last 28 days 8. Leukaemia 9. Emergency operation 10. Proven infection within the last 7 days 11. Known infection of hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or positive result during pre-operative screening 12. Allergy against any ingredients of the trial drug 13. Autoimmune diseases 14. Intake of immunosuppressive drugs up to 4 weeks before surgery 15. Cardiac arrhythmia without adequate therapy 16. Unstable angina pectoris 17. Symptomatic congenital heart defect 18. History of thrombosis or thromboembolic incidents 19. Body weight below 50 kg 20. Thrombocytes below or equal to 100,000/µl on the day before surgery 21. Neutrophils below or equal to 1,500/µl on the day before surgery 22. Haemoglobin below or equal to 8 g/dl on the day before surgery 23. Bilirubin above 2 g/dl on the day before surgery 24. Creatinine above 1.5 g/dl on the day before surgery 25. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) above 90 U/l on the day before surgery
Date of first enrolment	26/10/2008
Date of final enrolment	16/04/2011

Locations

Countries of recruitment

Germany

Study participating centre

Charité - Universitätsmedizin Berlin

Berlin
13353
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	07/12/2015		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

08/12/2015: Publication reference added.