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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Wounds and Injuries, Surgery--Complications

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral + Parenteral prophylaxis + Mechanical Bowel Preparation<br>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<br>* Extra dosage<br>Procedure: Colonic Surgery<br>* Colonic Surgery<br>Drug: Cefuroxime 750mg oral<br>* Oral prophylaxis<br>Drug: Metronidazole 250 MG Oral Tablet [Flagyl]<br>* Oral prophylaxis<br>Drug: Metronidazole 1 g Intravenous<br>* IV prophylaxis<br>Drug: Cefuroxime 1,5 g Intravenous<br>* IV prophylaxis<br>Drug: Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g Oral<br>* Laxative for bowel cleansing<br>|
| Active Comparator: Oral + Parenteral prophylaxis<br>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<br>* Extra dosage<br>Procedure: Colonic Surgery<br>* Colonic Surgery<br>Drug: Cefuroxime 750mg oral<br>* Oral prophylaxis<br>Drug: Metronidazole 250 MG Oral Tablet [Flagyl]<br>* Oral prophylaxis<br>Drug: Metronidazole 1 g Intravenous<br>* IV prophylaxis<br>Drug: Cefuroxime 1,5 g Intravenous<br>* IV prophylaxis<br>|

What is the study measuring?
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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 |