Probiotics in the Prevention of Complications After Colorectal Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Postoperative Complications

Intervention / Treatment
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* Dietary Supplement: Probiotics
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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].

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Capsules of powdered glucose polymer given one capsule every 12 hours for 15 days | Dietary Supplement: Placebo<br>* Glucose powder<br>* Other names: Placebo capsules;|
| Active Comparator: Probiotics<br>Capsules containing Lactobacillus acidophilus LA-5 [1.75x10^9 cfu], Lactobacillus plantarum [0.5x10^9 cfu], Bifidobacterium lactis BB-12 [1.75x10^9cfu], and Saccharomyces boulardii [1.5x10^9] per capsule. One capsule is given every 12 hours for 15 days | Dietary Supplement: Probiotics<br>* Probiotics are prepared in capsule form<br>* Other names: Lactobacillus, Bifidobacterium and Saccharomyces boulardii;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications | The total of postoperative complications observes in each study group. These comprise: any anastomotic leakage; abdominal wound infection and dehiscence; organ specific infections, such as pneumonia, urinary tract and central vein port-site infections, and systemic infections [bacteraemia, fungal infections] as regularly defined by positive cultures, radiograms, increased white blood cell count or purulent material discharge; sepsis and septic shock | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minor complications | Rate of minor events in each group. These comprise peripheral vein thrombosis or pulmonary embolism and cardio-pulmonary or renal insufficiency. Moreover, the number of days on mechanical ventilation, in postoperative ileus, of total hospitalization, as well as 30-day mortality is taken into account. | 30 days | 
| Cytokine levels | Measurement of serum cytokines in subgroups of patients | 4 days | 
| Cytokine gene transcripts | Measurement of gene transcripts in whole blood in subgroups of patients | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infections, anastomotic leakage