Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05164887 |
| Other study ID # |
1.0 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2020 |
| Est. completion date |
November 30, 2022 |
Study information
| Verified date |
April 2023 |
| Source |
S.Eugenio Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Aim of this study is to implement the intestinal microbiota by perioperative administration
of probiotics, oral antibiotics and low volume mechanical preparation in order to reduce the
incidence of colorectal anastomotic leaks and dehiscences.
Description:
Anastomotic leaks and dehiscences are still the most frequent complication of colorectal
surgery and have a multifactorial etiology.
Microbiota refers to the totality of microorganisms in a defined environment. The Microbiome
represents the set of genomes of all microorganisms and its environmental relationships. The
microbiome performs various and important functions, but above all it contributes to
maintaining the integrity of the mucous barrier of the intestinal epithelium.
The composition, biodiversity and functions of the intestinal microbiota vary both
longitudinally along the entire intestinal tract from the mouth to the anus, and radially
from the muco-epithelial layer to the intestinal lumen. This biodiversity fluctuates with
daily variations following various conditions such as diet, physical activity, interactions
with people and animals, etc., but remains stable in healthy subjects.
Particular conditions can determine a phenotypic shift of some bacterial families with the
development of species with different characteristics, potentially pathogenic which can favor
the onset of fistulas and anastomotic dehiscences in experimental setting.
It is known experimentally that the surgical act alone causes a greater change in the
composition of the intestinal microbiota. The way in which surgical stress alters the
microbiome lies in the mechanisms which the host and the microorganisms communicate. It has
recently been shown that mechanical bowel preparation and the administration of antibiotics
have an influence on the microbiome. In particular, the mechanical preparation with
polyethylene glycol (PEG) and oral antibiotics (OA) can constitute a positive element for
surgical outcomes, while intravenous antibiotics very often affect microbiota negatively.
The intestinal flora influence the healing of intestinal anastomoses and non-pathogenic
saprophytes allow anastomoses to withstand increased endoluminal pressures. Based on this, it
has been shown that the postoperative implementation of bifidobacteria improves functional
recovery, reduces the inflammatory response and improves the composition of the fecal
microbiota in patients undergoing colorectal surgery.
Based on these considerations, this study aims to modify the preoperative preparation by
implementing the intestinal microbiota in order to evaluate the incidence of anastomotic
leaks.
The patient's treatment will be divided into 3 phases: preoperative, intraoperative and
postoperative.
Preoperative treatment The preoperative phase runs from the fifth preoperative day (-5) to
day -1.
In this phase, patients will undergo microbiota implementation through preoperative
preparation consisting of:
- Oral probiotics: Streptococcus thermophilus; Bifidobacterium brevis; Bifidobacterium
longum; Bifidobacterium infantis; Lactobacillus acidophilus; Lactobacillus plantarum;
Lactobacillus paracasei; Lactobacillus delbrueckii subsp. Bulgaricus (VSL # 3) 4,4gr,
equal to 450 billion live bacterial cells, every 12 hours from the day -5.
- Oral antibiotic prophylaxis with Amoxicillin / Ac. Clavulanic (Augmentin), 1g every 12
hours + Metronidazole (Flagyl), 250 mg every 8 hours in the day -1.
- Mechanical preparation with Polyethylene Glycol - low volume.
Intraoperative treatment - Surgical technique Under general anesthesia and hemodynamic
monitoring, pneumoperitoneum induction and positioning of the trocars necessary for the
execution of the surgery will be carried out. The number and location of the trocars will be
determined by the type of intervention to be performed and the operator's preferences. After
an abdominal exploration, we will continue with the resective phase of the intervention
depending on the location of the disease and in compliance with the oncological radicality
criteria. The anastomosis will be performed according to the principles of good
vascularization and reconstruction without tension or torsion.
The anastomosis will be:
- Intracorporeal (mechanical / manual) if ileo-colic.
- Intra- or extra-corporeal (mechanical or manual respectively) if colocolic, after
resection of the transverse, splenic or segmental flexure of the left colon.
- Transanal (mechanical) if colorectal, after left hemicolectomy, sigmoidectomy or
resection of the rectum (both intra- and subperitoneal).
The positioning of nasogastric tube, drains, bladder catheter, central vascular accesses,
whose management will be at the discretion of the operators, is subject to the Enhanced
Recovery After Surgery (ERAS®) principles in use in the centers participating in the study.
- Intraoperative phase On the morning of the surgery, antibiotics will be administered:
Amoxicillin / Ac. Clavulanic 1g + Metronidazole 250 mg orally, about 2 hours before the
induction of anesthesia.
Anastomotic endoluminal instillation of a dose (4.4 g) of the probiotic used in the
preoperative phase, diluted in 20cc of sterile physiological solution, will also be
performed. This dose will be equally distributed in the 2 intestinal stumps. The instillation
will take place using a special laparoscopic cannula.
Postoperative treatment The postoperative management of patients will be based on compliance
with Enhanced Recovery After Surgery (ERAS®) principles, where applicable (nasogastric tube
removal on first postoperative day, bladder catheter removal on first postoperative day,
early feeding, mobilization, etc.).
The oral antibiotic prophylaxis will be continued until day +1, while the administration of
probiotics will take place until day +4.
