Parenteral Antibiotics Compared to Combination of Oral and Parenteral Antibiotics in Colorectal Surgery Prophylaxis (ORALEV)

Preoperative Oral Antibiotics and Surgical Site Infections in Colon Surgery Without Mechanical Bowel Preparation. A Prospective, Multicentre, Single Blinded, Randomized Trial (ORALEV Study)

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

Experimental group: Patients undergoing elective colorectal 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.

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

The antibiotic prophylaxis in this group will be composed of:

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

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.

There won´t be a placebo treatment. Subject compliance will be evaluated according to the usual practice in surgical care field

Study Overview

• Status: Completed
• Conditions: Surgical Wound Infection
• Intervention / Treatment: Drug: Extra dosage - cefuroxime (750mg) I.V; Procedure: Colorectal Surgery; Drug: Ciprofloxacin 750 mg oral; Drug: Metronidazole 250 mg oral; Drug: Cefuroxime 1.5 g Intravenous; Drug: Metronidazole 1 g Intravenous

• Study Type: Interventional
• Enrollment (Actual): 536
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall d´Hebron
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr. Josep Trueta
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain
      • Hospital de Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting colonic pathology
• The surgery is not contraindicated
• Diagnosis of colorectal neoplasia or diverticular disease with surgical indication (stenosis, chronic constipation, recurrent infections etc ..)
• Indication of segmentary resection or total colectomy
• Patients who agree to participate voluntarily in the study and signed an informed consent.

Exclusion Criteria:

• Patients who refuse to participate in the study.
• Patients undergoing mechanical colon preparation the day before surgery.
• Patients with rectal cancer
• Patients with intra-abdominal sepsis before surgery (abscess, diverticulitis).
• Patients who received preoperative antibiotics for any reason in the two weeks prior to surgery.
• Patients with inflammatory bowel disease (ulcerative colitis, Crohn's disease and indeterminate colitis)
• Patients presenting allergy to the drugs under study.
• Patients that will not strictly follow the assigned prophylaxis regimen
• Patients undergoing urgent surgery (<24h)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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: Colorectal Surgery; Both groups undergo colorectal surgery. This section does not include rectal surgery ( see Inclusion/exclusion criteria); Drug: Ciprofloxacin 750 mg oral; An oral antibiotic pattern of ciprofloxacin (750 mg / 12h, 2 doses) the day before surgery.; Drug: Metronidazole 250 mg oral; An oral antibiotic pattern of metronidazole (250 / 8h, 3 doses) the day before surgery.; Drug: Cefuroxime 1.5 g Intravenous; An intravenous antibiotic pattern of cefuroxime 1.5 g during anesthetic induction.; Drug: Metronidazole 1 g Intravenous; An intravenous antibiotic pattern of metronidazole 1 g during anesthetic induction.
Active Comparator: Only 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: Colorectal Surgery; Both groups undergo colorectal surgery. This section does not include rectal surgery ( see Inclusion/exclusion criteria); Drug: Cefuroxime 1.5 g Intravenous; An intravenous antibiotic pattern of cefuroxime 1.5 g during anesthetic induction.; Drug: Metronidazole 1 g Intravenous; An intravenous antibiotic pattern of metronidazole 1 g during anesthetic induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Direct Adverse Drug Reactions	Allergic reactions Intolerance •This morbidity problems are reported independently as a YES/NO variable	24 hours since the drug is taken
Occlusive problems	Intestinal occlusion, Anastomotic stenosis, Prolonged ileus(>5days),.... Occlusive problems, Iatrogenic problems, Impaired healing ( Anastomotic leak rate , intestinal fistula , vesical fistula, peritonitis...) Bleeding problems, Cardiac complications, Nephro-urinary complications, Respiratory complications, Vascular Complications, Gastrointestinal complications, Neurological complications, Local complications... •This morbidity problems are reported independently as a YES/NO variable	30 days from surgery
Iatrogenic problems	Damage to structures such as ureters, bowel loops artery / iliac vein .... •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
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
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
Respiratory complications	Pneumonia, Atelectasis, Pulmonary embolism, Respiratory distress syndrome ...; This is a Clinical measure always supported by image .; This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Vascular Complications	Deep venous thrombosis, phlebitis, thrombophlebitis, ...; This is a Clinical measure supported by more specific test if necessary .; This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
Gastrointestinal complications	Liver failure, gastrointestinal bleeding, severe malnutrition, ...; This is a Clinical measure supported by blood test and further test if necessary; 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
Local infection	Superficial, deep, body-cavity; This is a Clinical measure supported by image if necessary; This morbidity problems are reported independently as a YES/NO variable	30 days after surgery
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

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Investigators: Study Chair: Eloy Espin Basany, MD PhD, Hospital Universitari Vall d'Hebron Research Institute

Publications and helpful links

General Publications

• Espin Basany E, Solis-Pena A, Pellino G, Kreisler E, Fraccalvieri D, Muinelo-Lorenzo M, Maseda-Diaz O, Garcia-Gonzalez JM, Santamaria-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. Epub 2020 Apr 21. Erratum In: Lancet Gastroenterol Hepatol. 2020 Apr 30;:

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): November 10, 2018

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: July 21, 2015
• First Posted (Estimate): July 22, 2015

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 12, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Surgical Wound Infection; Postoperative Wound Infection; Colorectal Surgery Infection Prophylaxis
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Wounds and Injuries; Disease Attributes; Infections; Communicable Diseases; Surgical Wound; Surgical Wound Infection; Wound Infection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Metronidazole; Ciprofloxacin; Cefuroxime; Cefuroxime axetil
• Other Study ID Numbers: 2014-002345-21

Plan for Individual participant data (IPD)

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