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

Phase 4
Conditions
Wounds and Injuries
Surgery--Complications
Interventions
Procedure: Colonic Surgery
Drug: Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g Oral
Registration Number
NCT04161599
Lead Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Brief Summary

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.

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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
968
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationCefuroxime 750mg oralDrug: 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.
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationCefuroxime 1,5 g IntravenousDrug: 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.
Oral + Parenteral prophylaxisMetronidazole 1 g IntravenousDrug: 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.
Oral + Parenteral prophylaxisCefuroxime 1,5 g IntravenousDrug: 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.
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationCefuroxime (750mg) I.VDrug: 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.
Oral + Parenteral prophylaxisCefuroxime 750mg oralDrug: 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.
Oral + Parenteral prophylaxisMetronidazole 250 MG Oral Tablet [Flagyl]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.
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationMetronidazole 1 g IntravenousDrug: 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.
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationColonic SurgeryDrug: 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.
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationMetronidazole 250 MG Oral Tablet [Flagyl]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.
Oral + Parenteral prophylaxis + Mechanical Bowel PreparationSodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g OralDrug: 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.
Oral + Parenteral prophylaxisCefuroxime (750mg) I.VDrug: 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.
Oral + Parenteral prophylaxisColonic SurgeryDrug: 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.
Primary Outcome Measures
NameTimeMethod
Rate of Wound infection30 days

Superficial, deep, body-cavity This is a Clinical measure supported by image if necessary All the morbidity problems are reported independently

Secondary Outcome Measures
NameTimeMethod
Bleeding problems30 days after surgery

Hemoperitoneum, abdominal hematoma,anastomotic bleeding

•This morbidity problems are reported independently as a YES/NO variable

Iatrogenic problems30 days after surgery

Injury to structures such as ureters, bowel loops artery / veins .

•This morbidity problems are reported independently as a YES/NO variable

Local complications30 days after surgery

Hematoma, seroma, evisceration

This is a Clinical measure. This morbidity problems are reported independently as a YES/NO variable

Impaired healing30 days after surgery

This is a Clinical measure always supported by image tests. This morbidity problems are reported independently as a YES/NO variable

Occlusive problems30 days from surgery

Intestinal occlusion, Anastomotic stenosis, Postoperative ileus

Nephro-urinary complications30 days after surgery

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

Adverse events related to drugs (Harms)30 days after surgery

Any adverse event related with the drug

•This morbidity problems are reported independently as a YES/NO variable

Time to complete recovery30 days after surgery

Interval between hospital admission and complete recovery ("can be discharged")

Length of Hospital stayParticipants will be followed for the duration of hospital stay, an expected average of 7 days

Hospital stay since colorectal surgery is done

Cardiac complications30 days after surgery

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

Respiratory complications30 days after surgery

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

Neurological complications30 days after surgery

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.

Postoperative intestinal problems30 days after surgery

Postoperative diarrhoea, nausea and vomiting

Readmission30 days after surgery

Need to be readmitted after discharge

Reintervention30 days after surgery

Need to be reoperated

Perioperative HypovolemiaIntraoperative assessment

Signs or symptoms of hypovolemia not related with bleeding, as assessed by the anesthetist at surgery

Patient satisfaction with preparation receivedwithin the 30 days from surgery

Patient satisfaction with the preparation receivced, assessed with a Verbal Rating Scale (VRS) from 1 (minimum satisfaction) to 10 (maximum satisfaction)

Death30 days after surgery

Patient death for any cause and patient death in relation with treatment received

Anastomotic leak30 days after surgery

clinical, radiological or intraoperatively detected abdominal or pelvic leak or collection

Trial Locations

Locations (10)

General University Hospital of Patras

🇬🇷

Patra, Greece

Hospital Universitario Lucus Augusti

🇪🇸

Lugo, Spain

Hospital General Universitario Vall d´Hebron

🇪🇸

Barcelona, Barcelona, Spain, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Spain

Humanitas Research Hospital

🇮🇹

Rozzano, Italy

Royal Marsden Hospital, Imperial College of London

🇬🇧

London, United Kingdom

Tomsk Oncological Hospital

🇷🇺

Tomsk, Russian Federation

Hospital Universitario Cruces

🇪🇸

Cruces, Spain

Hospital de Bellvitge

🇪🇸

Barcelona, Hospitalet De Llobregat, Barcelona, Spain, Spain

Jinling Hospital

🇨🇳

Nanjing, China

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