Probiotics in the Prevention of Complications After Colorectal Surgery

• ClinicalTrials.gov Identifier: NCT02313519
• Recruitment Status: Completed
• First Posted: December 10, 2014
• Last Update Posted: December 10, 2014
• Sponsor: Evangelos J. Giamarellos-Bourboulis, M.D.
• Collaborator: Aristotle University Of Thessaloniki
• Information provided by (Responsible Party): Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Postoperative Complications	Dietary Supplement: Probiotics; Dietary Supplement: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• 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 Start Date: April 2013
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Capsules of powdered glucose polymer given one capsule every 12 hours for 15 days	Dietary Supplement: Placebo; Glucose powder; Other Name: Placebo capsules
Active Comparator: Probiotics; 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; Probiotics are prepared in capsule form; Other Name: Lactobacillus, Bifidobacterium and Saccharomyces boulardii

Outcome Measures

Primary Outcome Measures :

1. Postoperative complications [ Time Frame: 30 days ]
   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

Secondary Outcome Measures :

1. Minor complications [ Time Frame: 30 days ]
   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.
2. Cytokine levels [ Time Frame: 4 days ]
   Measurement of serum cytokines in subgroups of patients
3. Cytokine gene transcripts [ Time Frame: 4 days ]
   Measurement of gene transcripts in whole blood in subgroups of patients

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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].

Contacts and Locations

Sponsors and Collaborators

Evangelos J. Giamarellos-Bourboulis, M.D.

Aristotle University Of Thessaloniki

Investigators

• Study Chair: Katerina Kotxampassi, MD, PhD; AXEPA University of Thessaloniki, 1st Department of Propedeutic Surgery, Thessaloniki, Greece
• Principal Investigator: Evangelos Giamarellos-Bourboulis, MD, PhD; University of Athens, 4th Department of Internal Medicine, Athens, Greece

More Information

Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Evangelos J. Giamarellos-Bourboulis, M.D., Associate Professor of Medicine, University of Athens
• ClinicalTrials.gov Identifier: NCT02313519
• Other Study ID Numbers: LACT002
• First Posted: December 10, 2014
• Last Update Posted: December 10, 2014
• Last Verified: December 2014

Keywords provided by Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens:

Infections; anastomotic leakage

Additional relevant MeSH terms:

Postoperative Complications; Pathologic Processes