| Objective: |
The study will compare the rate of Surgical Site Infections (SSI) between two groups of patients undergoing colonic surgery (NO rectal surgery).
All patients will receive preoperative oral antibiotics; the experimental group will receive mechanical bowel preparation (MBP) with Citrafleet®, whereas the control group will not receive MBP. |
| Aim: |
Primary Aim: Surgical site infections (SSI) (defined as the sum of superficial, deep, and organ-space infections according to CDC criteria) with vs without MBP, after colonic surgery. Complications will be defined as any infection of the surgical wound occurring within 30 days from surgery, and they will be assessed by means of clinical exam +/- imaging and microbiology.
Secondary Aims: 30-day postoperative surgical complications (ileus requiring or not reoperation, anastomotic leak, urinary tract infection), medical complications (adynamic ileus, respiratory, cardiac, neurologic, vascular complications), acute kidney failure. Patient satisfaction with the preparation. Complications will be classified according to Clavien-Dindo and the Cumulative Complication Index. Mortality. Safety of IV and oral antibiotics and of the MBP will be assessed and adverse events reported as required. Secondary aims also include the assessment of patients at 60-day follow-up and at 5-year follow-up, in order to detect late morbidity, re-admission and reoperation for septic and non-septic reasons, survival.
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| Methods: |
Phase IV, prospective, multicentric, international, randomised, controlled, practical, adaptive, trial. Two parallel groups will be established, for which the treatment will be decided by means of 1:1 randomisation. Randomisation will reduce the risk of selection bias, favouring a balanced distribution of the subjects among groups according to the known confounding factors. The assessment of the primary aim (SSI) will be performed by collaborators who are blinded to the treatment received.
Overall, 686 patients (343 randomised to the experimental treatment and 343 randomised to control treatment), enrolled at the hospitals which participate in the study, scheduled to undergo elective colonic surgery. Patients will be enrolled at an outpatient clinic. After signing the informed consent, patients will be randomised to one of the two treatment arms, if the expected surgical procedure includes elective segmental or total colectomy.
Enrolment start: February 2021. Enrolment conclusion: May 2022 - depending on enrorllment status..
Follow-up for the primary aim will end 30 days after surgery for the last included patient. The study can be prolonged or terminated earlier if the planned sample size is achieved or according to the interim analysis. Ancillary studies will assess complications 2 months and 5 years after treatment. |
| Reason for International Trial: |
Even if with contradictory findings, mechanical bowel preparation (MBP) is usually adopted in patients scheduled to undergo rectal resection]. The role of MBP in patients needing colonic surgery is yet to be elucidated.
We decided to assess the impact of MBP on the incidence of surgical site infections (SSI) after colonic surgery, because the actual utility of the preparation has been questioned by available evidences, and no prospective, randomised, adequately designed and powered studies are available on the topic.
All included patients will undergo both oral and IV antibiotic prophylaxis, for the following reasons:
a) the findings of a prospective randomised controlled trial (RCT) that has been recently been published by our group, which showed the superiority of oral + IV antibiotics in reducing SSI compared with IV only, without MBP use in any of the groups [1]
b) it represents an effective approach according to some studies, and it could reduce morbidity and mortality associated with colonic surgery (infections, length of stay, postoperative pain)
c) no RCTs are available, comparing oral antibiotic prophylaxis with or without MBP.
Concerning MBP, which will be administered to one of the two groups, the Sodium Picosulfate will be used (Citrafleet®). National and International Guidelines recommend its use for bowel cleansing. It represents a safe formulation, which is routinely used at the centres that will koin the study.
Concerning antibiotics used in both groups, the combination of antibiotics was decided according to pharmacokinetics, to the recommendations of the Infectious Disease Unit of the Hospital Universitario Valle de Hebrón, and to the results of the our previously published study [1].
The expected benefit would consist of combined effect of oral antibiotics with MBP to reduce SSI, as compared with oral antibiotics only, when IV antibiotics are routinely administered.
Reference
1. Espin Basany E, Solís-Peña A, Pellino G, Kreisler E, Fraccalvieri D, Muinelo-Lorenzo M, Maseda-Díaz O, García-González JM, Santamaría-Olabarrieta M, Codina-Cazador A, Biondo S. Preoperative oral antibiotics and surgical-site infections in colon surgery (ORALEV): a multicentre, single-blind, pragmatic, randomised controlled trial. Lancet Gastroenterol Hepatol
. 2020 Aug;5(8):729-738. doi: 10.1016/S2468-1253(20)30075-3. |