Condition category
Cancer
Date applied
10/08/2007
Date assigned
06/11/2007
Last edited
25/11/2008
Prospective/Retrospective
Prospectively 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 Henry Paul Redmond

ORCID ID

Contact details

Department of Surgery
Cork University Hospital
Wilton
Cork
-
Ireland
henry.redmond@hse.ie

Additional identifiers

EudraCT number

2008-005570-12

ClinicalTrials.gov number

Protocol/serial number

RCSI SR&D 09/08/07-1

Study information

Scientific title

Acronym

Study hypothesis

Please note that as of 25/11/2008 this record was amended to include details of an updated protocol. All updates can be found under the relevant section with the above update date. Please also note that the anticipated start and end dates of this trial have also been updated. The intial study dates at the time of registration were as follows:
Initial anticipated start date: 01/01/2008
initial anticipated end date: 31/12/2009

Please also note that the target number of participants has been updated from the initial target number of 280 participants to the current target of 60 participants.

Amended as of 25/11/2008:
To examine the role of taurolidine in attenuating the surgically-induced systemic endotoxaemia and subsequent inflammatory response thereby assessing its anti-neoplastic effects in patients undergoing surgery for non-metastatic colon cancer and prevention of (micro) metastases.

Initial information at time of registration:
To assess the role of taurolidine in the following:
1. The attenuation of the pro-inflammatory cytokine response in the perioperative period in patients with colon cancer
2. The reduction of post-operative infectious complications
3. The reduction of post-operative respiratory complications
4. The return of Gastro-Intestinal (GI) function post-operatively
5. Post-operative recovery and length of hospital stay
6. Preventing tumour recurrence

Ethics approval

Ethics Committee of University College Cork (Ireland) granted provisional approval on the 11th September 2007 pending authorisation from the Irish Medicines Board (IMB). The IMB gave their approval on the 8th September 2008 (added 25/11/2008).

Study design

Open, prospective, multi-centre, randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Colon cancer

Intervention

Amended as of 25/11/2008:
From induction of anaesthesia, patients will be administered 250 ml of 2% taurolidine or normal saline four times daily intravenously for four days.

Initial information at time of registration:
From induction of anaesthesia, patients will be administered 250 ml of 2% taurolidine or the same volume of normal saline intravenously three times a day for three days.

Intervention type

Drug

Phase

Not Specified

Drug names

Taurolidine

Primary outcome measures

Amended as of 25/11/2008:
1. Percent change in taurolidine as compared to control group in mean day 1 IL-6 relative to mean baseline IL-6. Mean day-1 lL-6 defined as mean of available values from (+3, +6, +24 hours post-induction). Mean baseline defined as mean of available pre-op IL-6 levels.

Initial information at time of registration:
The following will be measured twice pre-operatively and at 4 hours, 24 hours, 48 hours, 3 days and 5 days post-operatively:
1. Pro-inflammatory cytokine levels (Interleukin-6 [IL-6], Interleukin-1-beta [IL-1beta], Tumour Necrosis Factor-alpha [TNF-alpha], Vascular Endothelial Growth Factor [VEGF])
2. Anti-inflammatory cytokine levels (Interleukin-1-Receptor Antagonist [IL-1RA], Interleukin-10 [IL-10])
3. C-Reactive Protein (CRP)
4. Endotoxin/Lipopolysaccharides (LPS) level

The following will be measured twice pre-operatively and at 24 hours and 5 days post-operatively:
5. Natural Killer (NK) Cell and Cytotoxic T-Lymphocyte (CTL) cytotoxic activity
6. Neutrophil/monocyte receptor expression (CD11b, CD14, Toll-Like Receptor-4 [TLR4])

Secondary outcome measures

Amended as of 25/11/2008:
1. Laboratory endpoints:
1.1. Percent change in taurolidine as compared to control group in mean day 2 and day 3 IL-6 relative to mean baseline Il-6. Mean day 2/day 3 defined as available IL-6 from 48 and 72 hours post-induction.
1.2. Percent change in taurolidine as compared to control group in mean available day 1 to day 3 versus mean baseline IL-10, endotoxin level, and C-reactive protein (CRP)
2. Clinical endpoints:
2.1. Comparison of Taurolidine with control group with regard to occurrence and severity of post-operative infections over 10 days post-operatively or until hospital discharge
2.2. Time to bowel functional recovery defined as time to first flatus or return of bowel sounds
2.3. Comparison of taurolidine with control group with regard to analgesic requirements (using ordinal ranking scale) and self assessed pain control using visual analogue scale at 24 and 72 hours post-induction
2.4. Percent tumour recurrence at 12 months following operation in taurolidine as compared to control group

Tertiary outcomes:
Percent change in taurolidine compared to control group in mean available day 1 - day 3 versus mean baseline:
1. Inflammatory cytokine levels (tumour necrosis factor alpha [TNF-a], vascular endothelial growth factor [VEGF], interleukin-1 receptor antagonist [IL-1ra], IL-1beta)
2. Natural Killer (NK) cell and cytotoxic T-lymphocyte (CTL) cytotoxic activity
3. Neutrophil/monocyte receptor expression (cluster of differentiation-14 [CD14], cluster of differentiation-11b [CD11b], toll-like receptor-4 [TLR4])

Safety endpoints:
Comparison of routine haematological and biochemical data at day 1, 2, 3, 5, hospital discharge, and 1 month. Clinical status at hospital discharge, 1, 6 and 12 months.

Initial information at time of registration:
1. Post-operative pain scores (Visual Analogue Scales [VAS])
2. Post-operative GI function (time to first flatus and to bowel sounds)
3. Post-operative respiratory function/infections (clinical)
4. Clinical wound infection rate
5. Length of hospital stay
6. Survival at 1 and 2 years
7. Time to tumour recurrence (radiological)

Overall trial start date

01/11/2008

Overall trial end date

01/06/2009

Reason abandoned

Eligibility

Participant inclusion criteria

Initial information at time of registration:
1. Patients of both genders who are 18 to 75 years of age
2. Patients with a solitary, non-metastatic extraperitoneal colonic tumour that already has been histologically confirmed
3. Patient has given full written informed consent
4. Elective setting

Added as of 25/11/2008:
5. Negative pregnancy test in women of childbearing age

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

Amended as of 25/11/2008:
1. Rectal tumours (within 15 cm of the anal orifice)
2. Known allergy to taurolidine/taurine
3. Pregnant and lactating women
4. Liver disease:
4.1. Abnormal liver function tests (LFTs) greater than 2 times upper limit of normal (ULN)
4.2. International normalised ratio (INR) greater than 1.5
5. Renal disease:
5.1. Creatinine greater than 180 (women), greater than 150 (men)
5.2. Serum sodium less than 132 or greater than 145
6. Blood dyscrasia:
6.1. Neutropenia less than 1500 cells/cm^3
6.2. Thrombocytopenia less than 100,000 cells/cm^3
7. Intestinal obstruction
8. Infiltration of adjacent organs
9. Tumour diameter greater than 8 cm on computed tomography (CT) scan
10. Severe obesity (body mass index greater than 32 kg/m^2)
11. Operative risk greater than American Society of Anaesthesiologists (ASA) - III
12. Another cancer/malignant disease other than non melanoma skin cancer
13. Coexisting active inflammatory disorder (including active Rheumatoid Arthritis [RA], Inflammatory Bowel Disease [IBD], Systemic Lupus Erythematosus [SLE])
14. Immunocompromised:
14.1. Corticosteroids
14.2. Immunosuppressive drugs
14.3. Patients with human immunodeficiency virus (HIV), chronic active hepatitis B or C virus
15. Active infection

Initial information at time of registration:
1. Known allergy to taurolidine/taurine
2. Pregnancy and lactation
3. Liver disease (abnormal Liver Function Test [LFT's] results or International Normalised Ratio [INR] greater than 1.5)
4. Renal disease
5. History of electrolyte imbalance
6. Blood dyscrasia (neutropenia less than 1500 cells/cm^3, thrombocytopenia less than 100,000 cells/cm^3)
7. Intestinal obstruction
8. Infiltration of adjacent organs
9. Tumour diameter greater than 8 cm on Computerised Tomography (CT) scan
10. Severe obesity (body mass index greater than 32 kg/m^2)
11. Operative risk greater than American Society of Anaesthesiologists (ASA) grade III
12. Another cancer/malignant disease
13. Another chronic inflammatory disorder (e.g. Rheumatoid Arthritis [RA], Inflammatory Bowel Disease [IBD], Systemic Lupus Erythematosus [SLE])
14. Immunocompromised
15. Active infection

Recruitment start date

01/11/2008

Recruitment end date

01/06/2009

Locations

Countries of recruitment

Ireland

Trial participating centre

Department of Surgery
Cork
-
Ireland

Sponsor information

Organisation

Geistlich Pharma AG (Switzerland)

Sponsor details

Bahnhofstrasse 40
Wolhusen/LU
CH-6100
Switzerland
r.w.pfirrmann@swissonline.ch

Sponsor type

Industry

Website

http://www.geistlich.ch/

Funders

Funder type

Industry

Funder name

Geistlich Pharma AG (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

Additional files

Editorial Notes