Clinical trial NCT02313519: Probiotics in the Prevention of Complications After Colorectal Surgery
Official title: A Randomized Clinical Study of the Efficacy of a Formulation of Four Probiotics for the Prevention of Post-operative Complications in Patients Undergoing Colorectal Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Complications
Keywords: Infections
anastomotic leakage
Lead sponsor: University of Athens
Sponsor class: OTHER
Collaborators: name: Aristotle University Of Thessaloniki
First posted: 2014-12-10
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Based on the need of large-scale, trials to explore the use of probiotics to reduce post-operative complication rate, a randomized controlled trial is designed to investigate the impact of a probiotics treatment protocol on postoperative morbidity in an open elective colonic surgery cohort. The major objective is reduction of post-operative complications after 30 days.

Detailed description: Major colorectal surgery, i.e. surgery involving a wide colon resection and/or a very low anastomosis, remains problematic, despite great advances in medico-pharmaceutical treatment, improvement in surgical techniques, and sophisticated postoperative management. Such surgery is still accompanied by an unacceptably high morbidity of 15% to 23.2% leading to an increase in the number of ventilatory support days, prolongation of total hospital stay, significantly higher medical costs, patient suffering, and, unfortunately mortality. Worse than this, nowadays, infections and sepsis are by far the most common morbidities, either as initial cause or as a consequence of another complication, such as anastomotic leakage. Ongoing clinical studies have reported probiotic therapies to be beneficial in elective surgery cases, since they have been shown to successfully modulate the GI flora in a plethora of medical settings and in critically ill and trauma patients. More precisely, recent randomized controlled studies and meta-analyses in elective surgery and abdominal surgery patients have demonstrated that the perioperative use of probiotics is safe and reduces both the incidence of postoperative wound infections, sepsis, post-operative pneumonia and other infections, and the necessary duration of hospital stay and length of antibiotic therapy. However, there exist few controlled, large-scale, trials comparing the current standard treatment with the probiotic concept and showing the superiority of the latter in colonic surgery with regard to a reduced complication rate. Therefore, the investigators decided to conduct a randomized controlled trial to investigate the impact of a probiotics treatment protocol on postoperative morbidity in an open elective colonic surgery cohort. The major objective is to evidence a reduction in 30-day infectious, surgery-related morbidity: any surgical site infection; organ specific infections; systemic infections and anastomotic leakage. Minor objectives related to the reduction in other non-infectious complications, as well as the assessment of outcome indicators such as the number of days in postoperative ileus, on mechanical ventilation, stay in ICU, total hospitalization and mortality in the 30-day post-operative period.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Acceptable nutritional status and programmed for open surgery for colorectal cancer.
* Operation by the same consultant either as surgeon or as the primary assistant.

Exclusion Criteria:

* Inability to provide written informed consent
* The need only for emergency or palliative surgery
* American Society of Anaesthesiologists (ASA) class of IV
* Pregnancy or lactation
* Inflammatory bowel disease
* Use of antibiotics during the last 10 days before surgery
* Recent steroid therapy or preoperative neoadjuvant chemotherapy or radiotherapy
* Pre-existing signs of bacterial \[white cell count, body temperature\] or viral infection \[hepatitis B or C, human immunodeficiency virus, cytomegalovirus\].

Primary outcomes:
measure: Postoperative complications
timeFrame: 30 days
Secondary outcomes:
measure: Minor complications
timeFrame: 30 days
measure: Cytokine levels
timeFrame: 4 days
measure: Cytokine gene transcripts
timeFrame: 4 days
Other outcomes:
Locations:
Study officials:
affiliation: AXEPA University of Thessaloniki, 1st Department of Propedeutic Surgery, Thessaloniki, Greece
name: Katerina Kotxampassi, MD, PhD
role: STUDY_CHAIR
affiliation: University of Athens, 4th Department of Internal Medicine, Athens, Greece
name: Evangelos Giamarellos-Bourboulis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giamarellos-Bourboulis EJ, Bengmark S, Kanellakopoulou K, Kotzampassi K. Pro- and synbiotics to control inflammation and infection in patients with multiple injuries. J Trauma. 2009 Oct;67(4):815-21. doi: 10.1097/TA.0b013e31819d979e.
citation: Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg. 2006 Oct;30(10):1848-55. doi: 10.1007/s00268-005-0653-1.
citation: Kotzampassi K, Stavrou G, Damoraki G, Georgitsi M, Basdanis G, Tsaousi G, Giamarellos-Bourboulis EJ. A Four-Probiotics Regimen Reduces Postoperative Complications After Colorectal Surgery: A Randomized, Double-Blind, Placebo-Controlled Study. World J Surg. 2015 Nov;39(11):2776-83. doi: 10.1007/s00268-015-3071-z.