Condition category
Haematological Disorders
Date applied
05/12/2008
Date assigned
27/02/2009
Last edited
08/12/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Claudia Spies

ORCID ID

Contact details

Augustenburger Platz 1
Berlin
13353
Germany
+49 (0)30 450 551001
claudia.spies@charite.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

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

Acronym

ART VI

Study hypothesis

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

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)

Study design

Prospective randomised double-blinded double-dummy placebo-controlled monocentre pilot study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Primary outcome measures

HLA-DR expression of monocytes on the first 5 post-operative days

Secondary outcome measures

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)

Overall trial start date

13/05/2008

Overall trial end date

16/04/2011

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

63

Participant 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

Recruitment start date

26/10/2008

Recruitment end date

16/04/2011

Locations

Countries of recruitment

Germany

Trial participating centre

Charité - Universitätsmedizin Berlin
Berlin
13353
Germany

Sponsor information

Organisation

Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)

Sponsor details

Universitaetsklinik fur Anasthesiologie mit Schwerpunkt operative Intensivmedizin
Augustenburger Platz 1
Berlin
13353
Germany
+49 (0)30 450 551001
claudia.spies@charite.de

Sponsor type

Hospital/treatment centre

Website

http://anaesthesieintensivmedizin.charite.de/

Funders

Funder type

Hospital/treatment centre

Funder name

Charité Universitätsmedizin Berlin

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

Germany

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in http://www.ncbi.nlm.nih.gov/pubmed/26641243

Publication citations

Additional files

Editorial Notes

08/12/2015: Publication reference added.