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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. (ORALEV2)

Primary Purpose

Wounds and Injuries, Surgery--Complications

Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Cefuroxime (750mg) I.V
Colonic Surgery
Cefuroxime 750mg oral
Metronidazole 250 MG Oral Tablet [Flagyl]
Metronidazole 1 g Intravenous
Cefuroxime 1,5 g Intravenous
Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g Oral
Sponsored by
Hospital Universitari Vall d'Hebron Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Wounds and Injuries

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jinling HospitalRecruiting
  • General University Hospital of PatrasRecruiting
  • Humanitas Research HospitalRecruiting
  • Tomsk Oncological HospitalRecruiting
  • Hospital General Universitario Vall d´HebronRecruiting
  • Hospital de BellvitgeRecruiting
  • Hospital Universitario CrucesRecruiting
  • Hospital Universitario Lucus AugustiRecruiting
  • Hospital Universitario Ramón y CajalRecruiting
  • Royal Marsden Hospital, Imperial College of London

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Oral + Parenteral prophylaxis + Mechanical Bowel Preparation

Oral + Parenteral prophylaxis

Arm Description

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: 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Local complications
Hematoma, seroma, evisceration This is a Clinical measure. This morbidity problems are reported independently as a YES/NO variable
Impaired healing
This is a Clinical measure always supported by image tests. This morbidity problems are reported independently as a YES/NO variable
Occlusive problems
Intestinal occlusion, Anastomotic stenosis, Postoperative ileus
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
Adverse events related to drugs (Harms)
Any adverse event related with the drug •This morbidity problems are reported independently as a YES/NO variable
Time to complete recovery
Interval between hospital admission and complete recovery ("can be discharged")
Length of Hospital stay
Hospital stay since colorectal surgery is done
Iatrogenic problems
Injury to structures such as ureters, bowel loops artery / veins . •This morbidity problems are reported independently as a YES/NO variable
Bleeding problems
Hemoperitoneum, abdominal hematoma,anastomotic bleeding •This morbidity problems are reported independently as a YES/NO variable
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
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
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.
Postoperative intestinal problems
Postoperative diarrhoea, nausea and vomiting
Readmission
Need to be readmitted after discharge
Reintervention
Need to be reoperated
Perioperative Hypovolemia
Signs or symptoms of hypovolemia not related with bleeding, as assessed by the anesthetist at surgery
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)
Death
Patient death for any cause and patient death in relation with treatment received
Anastomotic leak
clinical, radiological or intraoperatively detected abdominal or pelvic leak or collection

Full Information

First Posted
November 4, 2019
Last Updated
April 22, 2022
Sponsor
Hospital Universitari Vall d'Hebron Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04161599
Brief Title
Preoperative Oral Antibiotics With vs Without Mechanical Bowel Preparation to Reduce Surgical Site Infections Following Colonic Resection: an International Randomized Controlled Trial.
Acronym
ORALEV2
Official Title
Oral + Parenteral Antibiotic Prophylaxis Before Colonic Surgery With vs Without Mechanical Bowel Preparation: a Prospective, Multicentric, Randomised, Controlled Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitari Vall d'Hebron Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wounds and Injuries, Surgery--Complications

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
968 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oral + Parenteral prophylaxis + Mechanical Bowel Preparation
Arm Type
Experimental
Arm Description
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.
Arm Title
Oral + Parenteral prophylaxis
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cefuroxime (750mg) I.V
Intervention Description
Extra dosage
Intervention Type
Procedure
Intervention Name(s)
Colonic Surgery
Intervention Description
Colonic Surgery
Intervention Type
Drug
Intervention Name(s)
Cefuroxime 750mg oral
Intervention Description
Oral prophylaxis
Intervention Type
Drug
Intervention Name(s)
Metronidazole 250 MG Oral Tablet [Flagyl]
Intervention Description
Oral prophylaxis
Intervention Type
Drug
Intervention Name(s)
Metronidazole 1 g Intravenous
Intervention Description
IV prophylaxis
Intervention Type
Drug
Intervention Name(s)
Cefuroxime 1,5 g Intravenous
Intervention Description
IV prophylaxis
Intervention Type
Drug
Intervention Name(s)
Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g Oral
Intervention Description
Laxative for bowel cleansing
Primary Outcome Measure Information:
Title
Rate of Wound infection
Description
Superficial, deep, body-cavity This is a Clinical measure supported by image if necessary All the morbidity problems are reported independently
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Local complications
Description
Hematoma, seroma, evisceration This is a Clinical measure. This morbidity problems are reported independently as a YES/NO variable
Time Frame
30 days after surgery
Title
Impaired healing
Description
This is a Clinical measure always supported by image tests. This morbidity problems are reported independently as a YES/NO variable
Time Frame
30 days after surgery
Title
Occlusive problems
Description
Intestinal occlusion, Anastomotic stenosis, Postoperative ileus
Time Frame
30 days from surgery
Title
Nephro-urinary complications
Description
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
Time Frame
30 days after surgery
Title
Adverse events related to drugs (Harms)
Description
Any adverse event related with the drug •This morbidity problems are reported independently as a YES/NO variable
Time Frame
30 days after surgery
Title
Time to complete recovery
Description
Interval between hospital admission and complete recovery ("can be discharged")
Time Frame
30 days after surgery
Title
Length of Hospital stay
Description
Hospital stay since colorectal surgery is done
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 7 days
Title
Iatrogenic problems
Description
Injury to structures such as ureters, bowel loops artery / veins . •This morbidity problems are reported independently as a YES/NO variable
Time Frame
30 days after surgery
Title
Bleeding problems
Description
Hemoperitoneum, abdominal hematoma,anastomotic bleeding •This morbidity problems are reported independently as a YES/NO variable
Time Frame
30 days after surgery
Title
Cardiac complications
Description
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
Time Frame
30 days after surgery
Title
Respiratory complications
Description
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
Time Frame
30 days after surgery
Title
Neurological complications
Description
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.
Time Frame
30 days after surgery
Title
Postoperative intestinal problems
Description
Postoperative diarrhoea, nausea and vomiting
Time Frame
30 days after surgery
Title
Readmission
Description
Need to be readmitted after discharge
Time Frame
30 days after surgery
Title
Reintervention
Description
Need to be reoperated
Time Frame
30 days after surgery
Title
Perioperative Hypovolemia
Description
Signs or symptoms of hypovolemia not related with bleeding, as assessed by the anesthetist at surgery
Time Frame
Intraoperative assessment
Title
Patient satisfaction with preparation received
Description
Patient satisfaction with the preparation receivced, assessed with a Verbal Rating Scale (VRS) from 1 (minimum satisfaction) to 10 (maximum satisfaction)
Time Frame
within the 30 days from surgery
Title
Death
Description
Patient death for any cause and patient death in relation with treatment received
Time Frame
30 days after surgery
Title
Anastomotic leak
Description
clinical, radiological or intraoperatively detected abdominal or pelvic leak or collection
Time Frame
30 days after surgery
Other Pre-specified Outcome Measures:
Title
Complications at 60 days of follow up
Description
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
Time Frame
60 days after surgery
Title
Complications at 5 years of follow up
Description
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
Time Frame
5 years after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eloy Espín-Basany, MD PhD
Phone
934 893 000
Ext
6587
Email
eespin@vhebron.net
First Name & Middle Initial & Last Name or Official Title & Degree
Gianluca Pellino, MD, PhD
Phone
934 893 000
Ext
6587
Email
gpellino@vhebron.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eloy Espín-Basany, MD PhD
Organizational Affiliation
Hospital Universitario Valle de Hebron, Barcelona
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gianluca Pellino, MD, PhD
Organizational Affiliation
Hospital Universitario Valle de Hebron, Barcelona
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Alejandro Solís-Peña, MD, PhD
Organizational Affiliation
Hospital Universitario Valle de Hebron, Barcelona
Official's Role
Study Director
Facility Information:
Facility Name
Jinling Hospital
City
Nanjing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huajian Ren
Email
rhj1288@hotmail.com
Facility Name
General University Hospital of Patras
City
Patra
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesck Mulita
Facility Name
Humanitas Research Hospital
City
Rozzano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonino Spinelli
First Name & Middle Initial & Last Name & Degree
Annalisa Maroli
Facility Name
Tomsk Oncological Hospital
City
Tomsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugeniy Drozdov
Facility Name
Hospital General Universitario Vall d´Hebron
City
Barcelona
State/Province
Barcelona, Spain
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eloy Espín Basany, MD PhD
Phone
934 893 000
Ext
6587
Email
eespin@mac.com
First Name & Middle Initial & Last Name & Degree
María Martínez Lopez, MD
Email
m.martinez.21@vhebron.net
First Name & Middle Initial & Last Name & Degree
Gianluca Pellino, MD, PhD
Facility Name
Hospital de Bellvitge
City
Barcelona
State/Province
Hospitalet De Llobregat, Barcelona, Spain
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sebastiano Biondo, MD PhD
Phone
932 607 500
Facility Name
Hospital Universitario Cruces
City
Cruces
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José María García González
Facility Name
Hospital Universitario Lucus Augusti
City
Lugo
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manuel Muinelo
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Ocaña Jiménez
Email
jocajim@gmail.com
Facility Name
Royal Marsden Hospital, Imperial College of London
City
London
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christos Kontovounisios

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33872448
Citation
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.
Results Reference
result
PubMed Identifier
32818460
Citation
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.
Results Reference
derived

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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.

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