Clinical trial NCT05779254: SURGIcal COmplication and MIcrobiome ChangeS in Colorectal Surgery
Official title: Analysis of Mechanism on the Efficacy of Oral Antibiotic Prophylaxis in Elective Colon and Rectal Surgery With Primary Anastomosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Anastomotic Leak
Microbial Colonization
Keywords: Colorectal surgery
Anastomotic leak
Surgical site infection
Microbiome
Oral antibiotic prophylaxis
Lead sponsor: Uzsoki Hospital
Sponsor class: OTHER
Collaborators: name: University of Debrecen
name: Csolnoky Ferenc Hospital
First posted: 2023-03-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients undergoing planned colorectal surgery, whether open or laparoscopic, with circular suture anastomosis training are eligible for the study.

Brief summary: The microbiome, the collection of microorganisms that live in our gut, plays an important role in maintaining our health, proper nutrient absorption, nutrient turnover and immunity. After birth, a symbiotic relationship develops with the strains of bacteria that colonise our gut, and the presence and proportion of bacteria is individualised and highly variable.

A healthy bacterial flora is essential for the cells of the intestinal mucosa. Glycoproteins in the cell surface mucus coat are important nutrients for bacteria, while some bacterial strains supply mucosal cells with nutrient molecules (e.g. short-chain fatty acids) that are their essential energy source.

An abnormal change in the proportion of bacterial strains that make up the microbiome, dysbacteriosis, in which pathogenic bacteria proliferate at the expense of members of the normal flora, can cause a number of pathologies. Nutrient supply to the cells of the mucosa is reduced, making them more vulnerable and leading to various pathological conditions.

The microbiome and the essential nutrients they produce have also been found to play an important role in wound healing. A decrease in the diversity of the microbiome, an increase in the relative number of pathogenic bacteria and a decrease in the proportion of 'beneficial' bacteria increases the risk of surgical complications of infection and suture failure.

Detailed description: A number of risk factors have been identified that increase or decrease the risk of anastomotic leak. The risk of anastomotic failure is increased by anastomosis (lower third) close to the anus, tumour size greater than 5cm in colorectal carcinoma, surgical complications, smoking, diabetes, male gender, overweight, malnutrition (protein deficiency), heart disease requiring anticoagulation, time to surgery, American Society of Anaesthesiologist score, neoadjuvant treatment, corticosteroid use. The risk of suture failure is reduced by mechanical lining, intravenous and oral non-absorbable antibiotics. The microbiome also appears to have an impact on suture failure: lower diversity of bacteria in intraoperative specimens and an increase in the number of mucin-degrading Bacteroidaceae or Lachnospiraceae strains may be associated with higher anastomotic failure.

Eligibility criteria: Inclusion Criteria:

* Circular stapled anastomosis
* Planned surgery with colo-colic anastomosis
* No passage disorder, as it is confirmed at the first medical examination
* Not allergic to antibiotics
* Can receive a bowel preparation
* No proximal excluded intestine, i.e., the bowel preparation may be successful (ileostomy)

Exclusion Criteria:

* treated with antibiotics within 2 weeks before randomisation
* allergic to any of the medicines used
* under 18 years of age
* have suffered from abdominal sepsis within 6 months prior to recruitment
* pregnancy or breastfeeding
* been treated with steroids
* any form of chronic immunosuppression

Primary outcomes:
measure: Microbiome
timeFrame: postoperative 30 days
Secondary outcomes:
measure: Affecting factors on microbiome
timeFrame: postoperative 30 days
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Uzsoki Hospital
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Veszprém
country: Hungary
facility: Csolnoky Ferenc Kórház
Study officials:
affiliation: University of Debrecen
name: Peter Bay, Prof.
role: STUDY_DIRECTOR
References:
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citation: van Praagh JB, de Goffau MC, Bakker IS, van Goor H, Harmsen HJM, Olinga P, Havenga K. Mucus Microbiome of Anastomotic Tissue During Surgery Has Predictive Value for Colorectal Anastomotic Leakage. Ann Surg. 2019 May;269(5):911-916. doi: 10.1097/SLA.0000000000002651.
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citation: Nagata N, Tohya M, Fukuda S, Suda W, Nishijima S, Takeuchi F, Ohsugi M, Tsujimoto T, Nakamura T, Shimomura A, Yanagisawa N, Hisada Y, Watanabe K, Imbe K, Akiyama J, Mizokami M, Miyoshi-Akiyama T, Uemura N, Hattori M. Effects of bowel preparation on the human gut microbiome and metabolome. Sci Rep. 2019 Mar 11;9(1):4042. doi: 10.1038/s41598-019-40182-9.
citation: Papp G, Saftics G, Szabo BE, Baracs J, Vereczkei A, Kollar D, Olah A, Meszaros P, Duboczki Z, Bursics A. Systemic versus Oral and Systemic Antibiotic Prophylaxis (SOAP) study in colorectal surgery: prospective randomized multicentre trial. Br J Surg. 2021 Apr 5;108(3):271-276. doi: 10.1093/bjs/znaa131.
citation: Williamson AJ, Alverdy JC. Influence of the Microbiome on Anastomotic Leak. Clin Colon Rectal Surg. 2021 Nov 23;34(6):439-446. doi: 10.1055/s-0041-1735276. eCollection 2021 Nov.
citation: Di Segni A, Braun T, BenShoshan M, Farage Barhom S, Glick Saar E, Cesarkas K, Squires JE, Keller N, Haberman Y. Guided Protocol for Fecal Microbial Characterization by 16S rRNA-Amplicon Sequencing. J Vis Exp. 2018 Mar 19;(133):56845. doi: 10.3791/56845.
citation: Reuvers JRD, Budding AE, van Egmond M, Stockmann HBAC, Twisk JWR, Kazemier G, Abis GSA, Oosterling SJ; SELECT trial group. Gut Proteobacteria levels and colorectal surgical infections: SELECT trial. Br J Surg. 2023 Jan 10;110(2):129-132. doi: 10.1093/bjs/znac288. No abstract available.