Using taurolidine to attenuate the surgically-induced endotoxaemia and the subsequent inflammatory response in patients with primary non-metastatic colon cancer

ISRCTN	ISRCTN77829558
DOI	https://doi.org/10.1186/ISRCTN77829558
Clinical Trials Information System (CTIS)	2008-005570-12
Protocol serial number	RCSI SR&D 09/08/07-1
Sponsor	Geistlich Pharma AG (Switzerland)
Funder	Geistlich Pharma AG (Switzerland)

Submission date: 10/08/2007
Registration date: 06/11/2007
Last edited: 08/08/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Henry Paul Redmond
Scientific

Department of Surgery
Cork University Hospital
Wilton
Cork
-
Ireland

Email	henry.redmond@hse.ie

Study information

Primary study design	Interventional
Study design	Open prospective multi-centre randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Using taurolidine to attenuate the surgically-induced endotoxaemia and the subsequent inflammatory response in patients with primary non-metastatic colon cancer
Study objectives	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(s)	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).
Health condition(s) or problem(s) studied	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 Applicable
Drug / device / biological / vaccine name(s)	Taurolidine
Primary outcome measure(s)	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])
Key secondary outcome measure(s)	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)
Completion date	01/06/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	60
Key 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
Key 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
Date of first enrolment	01/11/2008
Date of final enrolment	01/06/2009

Locations

Countries of recruitment

Ireland

Study participating centre

Cork University Hospital

Cork
-
Ireland

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	06/08/2018		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

08/08/2018: Publication reference added.

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 initial 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.