Preoperative Oral Antibiotics With vs Without Mechanical Bowel Preparation to Reduce Surgical Site Infections Following Colonic Resection: an International Randomized Controlled Trial. (ORALEV2)

Oral + Parenteral Antibiotic Prophylaxis Before Colonic Surgery With vs Without Mechanical Bowel Preparation: a Prospective, Multicentric, Randomised, Controlled Trial.

The ORALEV Study found that preoperative oral antibiotics can reduce the incidence of surgical site infections after colonic resection, compared with no preparation.

The role of mechanical bowel preparation in patients needing colonic surgery is yet to be elucidated.

No randomised controlled trials have assessed the impact of mechanical bowel preparation combined with oral antibiotics on the incidence of surgical site infections after colonic surgery, compared with oral antibiotics only.

Study Overview

• Status: Recruiting
• Conditions: Wounds and Injuries; Surgery--Complications
• Intervention / Treatment: Drug: Cefuroxime (750mg) I.V; Procedure: Colonic Surgery; Drug: Cefuroxime 750mg oral; Drug: Metronidazole 250 MG Oral Tablet [Flagyl]; Drug: Metronidazole 1 g Intravenous; Drug: Cefuroxime 1,5 g Intravenous; Drug: Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g Oral

Detailed Description

International, multicentre, pragmatic, parallel-group, randomised controlled trial.

Routine antibiotics for the intravenous and oral prophylaxis of colorectal surgery will be used.

Experimental group: Patients undergoing elective colonic surgery that involves colonic resection.

The antibiotic prophylaxis in this group will be composed of:

An oral antibiotic pattern of ciprofloxacin (750mg / 12h, 2 doses) and metronidazole (250mg / 8h, 3 doses) the day before surgery, plus mechanical bowel preparation with Sodium picosulfate, light magnesium oxide, and anhydrous citric acid (10 mg - 3.5 g - 10.97 g per dose/ 2 doses the day before surgery) + An intravenous antibiotics pattern of cefuroxime 1,5 g and metronidazole 1 g at anesthetic induction.

Control group: Patients undergoing elective colonic surgery that involves colonic resection.

The antibiotic prophylaxis in this group will be composed of:

An oral antibiotic pattern of ciprofloxacin (750mg / 12h, 2 doses) and metronidazole (250mg / 8h, 3 doses)

+ An intravenous antibiotic pattern of cefuroxime 1,5 g and metronidazole 1 gr at anesthetic induction.

In both groups a second intravenous dose of cefuroxime (750mg) will be administered if the intraoperative time prolongs for more than three hours or if there is an intraoperative bleeding over 1000cc.

There will not be a placebo treatment. Subject compliance will be evaluated according to the usual practice in surgical care field

• Study Type: Interventional
• Enrollment (Anticipated): 968
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eloy Espín-Basany, MD PhD; Phone Number: 6587 934 893 000; Email: eespin@vhebron.net
• Study Contact Backup: Name: Gianluca Pellino, MD, PhD; Phone Number: 6587 934 893 000; Email: gpellino@vhebron.net

Study Locations

• China
  • Nanjing, China
    • Recruiting
    • Jinling Hospital
    • Contact: Huajian Ren; Email: rhj1288@hotmail.com
• Greece
  • Patra, Greece
    • Recruiting
    • General University Hospital of Patras
    • Contact: Francesck Mulita
• Italy
  • Rozzano, Italy
    • Recruiting
    • Humanitas Research Hospital
    • Contact: Annalisa Maroli
• Russian Federation
  • Tomsk, Russian Federation
    • Recruiting
    • Tomsk Oncological Hospital
    • Contact: Eugeniy Drozdov
• Spain
  • Cruces, Spain
    • Recruiting
    • Hospital Universitario Cruces
    • Contact: José María García González
  • Lugo, Spain
    • Recruiting
    • Hospital Universitario Lucus Augusti
    • Contact: Manuel Muinelo
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon Y Cajal
    • Contact: Juan Ocaña Jiménez; Email: jocajim@gmail.com
  • Barcelona, Spain
    • Barcelona, Barcelona, Spain, Spain, 08035
      • Recruiting
      • Hospital General Universitario Vall d´Hebron
      • Contact: Eloy Espín Basany, MD PhD; Phone Number: 6587 934 893 000; Email: eespin@mac.com
      • Contact: María Martínez Lopez, MD; Email: m.martinez.21@vhebron.net
      • Sub-Investigator: Gianluca Pellino, MD, PhD
  • Hospitalet De Llobregat, Barcelona, Spain
    • Barcelona, Hospitalet De Llobregat, Barcelona, Spain, Spain, 08907
      • Recruiting
      • Hospital de Bellvitge
      • Contact: Sebastiano Biondo, MD PhD; Phone Number: 932 607 500
• United Kingdom
  • London, United Kingdom
    • Not yet recruiting
    • Royal Marsden Hospital, Imperial College of London
    • Contact: Christos Kontovounisios

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of both genders, aged 18 years or above, with colonic disease without contraindications to surgical treatment, diagnosed with neoplasia or diverticular disease (diverticulosis with indication to elective surgery: stricture, chronic constipation), patients for whom a segmental or total colectomy is indicated.
• Patients who voluntarily accept to join the study and sign a dedicated written consent.
• Capability of understanding the study and take the medications prescribed.

Exclusion Criteria:

• Patients undergoing urgent surgery or no elective admission
• Patients who refuse to participate
• Patients with rectal disease or neoplasia
• Patients with pre-existing intrabdominal sepsis (abscess, acute diverticulitis)
• Patients who received preoperative antibiotic treatment for any other reasons during the two weeks before surgery
• Patients with Crohn's disease or ulcerative colitis
• Patients unlikely to adhere to the treatment prescribed
• Patients with allergy or contraindication to the medications used in the study
• Patients who need mechanical bowel preparation
• Patients with contraindication to bowel preparation used in the study (Citrafleet®):
• Patients with kidney failure needing haemodialysis or with hypermagnesemia
• Patients with severe heart failure
• Patients with gastric or duodenal ulcer
• Patients with mechanical obstruction
• Patients with toxic megacolon
• Patients with ascites or rhabdomyolysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral + Parenteral prophylaxis + Mechanical Bowel Preparation; Drug: Extra dosage - cefuroxime (750mg) I.V Procedure: Colonic Surgery Both groups undergo colonic surgery. This section does not include rectal surgery ( see Inclusion/exclusion criteria) Drug: Cefuroxime 750mg oral An oral antibiotic pattern of ciprofloxacin (750mg / 12h, 2 doses) the day before surgery. Drug: Metronidazole 250mg oral An oral antibiotic pattern of metronidazole (250mg / 8h, 3 doses) the day before surgery. Drug: Sodium picosulfate, magnesium oxide, citric acid anhydrous 15.08 g oral An oral laxative for bowel cleansing (2 doses) the day before surgery. Drug: Metronidazole 1 g Intravenous An intravenous antibiotic pattern of metronidazole 1 g during anesthetic induction. Drug: Cefuroxime 1,5 g Intravenous An intravenous antibiotic pattern of cefuroxime 1,5 g during anesthetic induction.	Drug: Cefuroxime (750mg) I.V; Extra dosage; Procedure: Colonic Surgery; Colonic Surgery; Drug: Cefuroxime 750mg oral; Oral prophylaxis; Drug: Metronidazole 250 MG Oral Tablet [Flagyl]; Oral prophylaxis; Drug: Metronidazole 1 g Intravenous; IV prophylaxis; Drug: Cefuroxime 1,5 g Intravenous; IV prophylaxis; Drug: Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g Oral; Laxative for bowel cleansing
Active Comparator: Oral + Parenteral prophylaxis; Drug: Extra dosage - cefuroxime (750mg) I.V In both groups a second intravenous dose of cefuroxime (750mg) will be administered if the intraoperative time elongates more than three hours or there is an intraoperative bleeding over 1000cc Procedure: Colonic Surgery Both groups undergo colonic surgery. This section does not include rectal surgery ( see Inclusion/exclusion criteria) Drug: Cefuroxime 750mg oral An oral antibiotic pattern of ciprofloxacin (750mg / 12h, 2 doses) the day before surgery. Drug: Metronidazole 250mg oral An oral antibiotic pattern of metronidazole (250mg / 8h, 3 doses) the day before surgery. Drug: Metronidazole 1 gr Intravenous An intravenous antibiotic pattern of metronidazole 1 g during anesthetic induction. Drug: Cefuroxime 1,5 g Intravenous An intravenous antibiotic pattern of cefuroxime 1,5 g during anesthetic induction.	Drug: Cefuroxime (750mg) I.V; Extra dosage; Procedure: Colonic Surgery; Colonic Surgery; Drug: Cefuroxime 750mg oral; Oral prophylaxis; Drug: Metronidazole 250 MG Oral Tablet [Flagyl]; Oral prophylaxis; Drug: Metronidazole 1 g Intravenous; IV prophylaxis; Drug: Cefuroxime 1,5 g Intravenous; IV prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Wound infection	Superficial, deep, body-cavity This is a Clinical measure supported by image if necessary All the morbidity problems are reported independently	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local complications	Hematoma, seroma, evisceration This is a Clinical measure. This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Impaired healing	This is a Clinical measure always supported by image tests. This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Occlusive problems	Intestinal occlusion, Anastomotic stenosis, Postoperative ileus	30 days from surgery
Nephro-urinary complications	Acute urinary retention, Acute renal failure, cystitis, pyelonephritis ... This is a Clinical measure supported by more specific tests if necessary. This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Adverse events related to drugs (Harms)	Any adverse event related with the drug •This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Time to complete recovery	Interval between hospital admission and complete recovery ("can be discharged")	30 days after surgery
Length of Hospital stay	Hospital stay since colorectal surgery is done	Participants will be followed for the duration of hospital stay, an expected average of 7 days
Iatrogenic problems	Injury to structures such as ureters, bowel loops artery / veins . •This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Bleeding problems	Hemoperitoneum, abdominal hematoma,anastomotic bleeding •This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Cardiac complications	Acute myocardial infarction, angor pectoris , atrial fibrillation, acute pulmonary edema This is a Clinical measure supported by more specific tests if necessary. This morbidity problems are reported independently as a YES/NO variable Cardiologist report will be required for including this items	30 days after surgery
Respiratory complications	Pneumonia, Atelectasia, Pulmonary embolism, ARDS This is a Clinical measure always supported by image . This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Neurological complications	Disorientation, cerebral vascular accident, This is a Clinical measure. This morbidity problems are reported independently as a YES/NO variable. Neurologist report will be required beyond disorientation.	30 days after surgery
Postoperative intestinal problems	Postoperative diarrhoea, nausea and vomiting	30 days after surgery
Readmission	Need to be readmitted after discharge	30 days after surgery
Reintervention	Need to be reoperated	30 days after surgery
Perioperative Hypovolemia	Signs or symptoms of hypovolemia not related with bleeding, as assessed by the anesthetist at surgery	Intraoperative assessment
Patient satisfaction with preparation received	Patient satisfaction with the preparation receivced, assessed with a Verbal Rating Scale (VRS) from 1 (minimum satisfaction) to 10 (maximum satisfaction)	within the 30 days from surgery
Death	Patient death for any cause and patient death in relation with treatment received	30 days after surgery
Anastomotic leak	clinical, radiological or intraoperatively detected abdominal or pelvic leak or collection	30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications at 60 days of follow up	Complications and events will be recorded at 60-day follow-up, including: Primary Outcome Measure, Outcome 1: Rate of Wound infection; Secondary Outcome Measures: Outcomes 2-6 / Outcomes 9-16 / Outcome 19	60 days after surgery
Complications at 5 years of follow up	Complications and events will be recorded at 5-year follow-up, including: Primary Outcome Measure, Outcome 1: Rate of Wound infection; Secondary Outcome Measures: Outcomes 2-6 / Outcomes 9-16 / Outcome 19; Readmission related with infections, with culture and antibiogram.; In patients with cancer, the following variables will also be collected: Local recurrence / Systemic recurrence	5 years after surgery

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Investigators: Study Chair: Eloy Espín-Basany, MD PhD, Hospital Universitario Valle de Hebron, Barcelona; Study Director: Gianluca Pellino, MD, PhD, Hospital Universitario Valle de Hebron, Barcelona; Study Director: Alejandro Solís-Peña, MD, PhD, Hospital Universitario Valle de Hebron, Barcelona

Publications and helpful links

General Publications

• Pellino G, Solis-Pena A, Kraft M, Huguet BM, Espin-Basany E. Preoperative oral antibiotics with versus without mechanical bowel preparation to reduce surgical site infections following colonic resection: Protocol for an international randomized controlled trial (ORALEV2). Colorectal Dis. 2021 Aug;23(8):2173-2181. doi: 10.1111/codi.15681. Epub 2021 May 12.
• Koskenvuo L, Sallinen V. Preoperative oral antibiotics in colon surgery. Lancet Gastroenterol Hepatol. 2020 Sep;5(9):801-802. doi: 10.1016/S2468-1253(20)30203-X. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 10, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Anticoagulants; Antiprotozoal Agents; Antiparasitic Agents; Chelating Agents; Sequestering Agents; Cathartics; Calcium Chelating Agents; Antacids; Metronidazole; Picosulfate sodium; Cefuroxime; Cefuroxime axetil; Magnesium Oxide; Citric Acid; Sodium Citrate
• Other Study ID Numbers: 2019-004283-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No