Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery
- Registration Number
- NCT02618720
- Lead Sponsor
- University Hospital, Clermont-Ferrand
- Brief Summary
To assess the effects of a combined antimicrobial prophylaxis using oral ornidazole (the day before surgery) and intravenous cephalosporin (before surgical incision) with that of intravenous cephalosporin alone (standard of care) in combination with oral placebo on the incidence of SSI within 30 days after elective colorectal surgery.
- Detailed Description
Surgical site infection (SSI) is a major cause of nosocomial infection in surgical patients, with the highest rates being reported (ranging from 15% to 30%) in colorectal surgery. SSI is an independent predictor of postoperative mortality and is associated with longer hospital stay, a 5-fold likelihood of postoperative readmission and a 2- to 3-fold increase in costs of care. Given the high prevalence and financial burden associated with SSI, American and European guidelines have been issued providing evidenced-based recommendations for the prevention of postoperative SSI. However, the prevalence of SSI remains high despite adherence to these guidelines and the application of evidence-based preventive measures.
Risk factors for SSI, whether modifiable or not, are mainly related to the patient condition (including age, severe comorbidity, diabetes, nutritional status, steroid use, smoking, and immunosuppression) and/or the surgical procedure (especially the surgical duration and skin disinfection). The prevention of SSI consists of several individual measures, and antibiotic prophylaxis covering aerobic and anaerobic bacteria is highly recommended in patients scheduled to elective colorectal resection, with French and European guidelines recommending the administration of intravenous cephalosporin within 30 minutes before surgical incision.
Recent data from retrospective studies and two meta-analyses of clinical trials provided compelling arguments that oral antibiotic administration before surgery in addition to conventional intravenous prophylaxis may be useful in further reducing by almost 75% the incidence of SSI (relative risk 0.55 \[CI95%: 0.41 to 0.74\]) after elective colorectal cancer surgery.
However, most of these studies have limitations precluding extrapolation of data into routine care, especially:
1. prolonged duration of intravenous antibiotic administration, which is no longer recommended in elective surgery;
2. the use of antibiotics for oral prophylaxis whose availability is limited;
3. only a few studies focused specifically on colorectal resection;
4. most studies did not include enhanced recovery after surgery (ERAS) programs, which was found to improve outcome following colorectal surgery, and
5. most studies have used mechanical bowel preparation, which is no longer recommended in colonic surgery while the issue still remains open for rectal surgery.
Investigators hypothesized that oral antibiotic prophylaxis using ornidazole, which has a spectrum of activity extended to most anaerobic bacteria and whose pharmacokinetic profile allows a single administration the day before surgery, in addition to intravenous antibiotic prophylaxis could be more effective than intravenous antibiotic prophylaxis alone using cephalosporin in reducing the incidence of SSI after elective colorectal surgery. Given the number of patients operated of colorectal surgery each year, the study is of significant clinical importance
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 920
- Age > 18
- Laparoscopic or non-laparoscopic elective colorectal surgery
- Non elective colorectal surgery (emergent surgery and/or reintervention or revision of a previous colorectal procedure)
- Significant concomitant surgical procedure (e.g., liver resection for metastasis)
- Bacterial infection at the time of surgery or antimicrobial therapy up to 2 weeks before surgery
- Inflammatory bowel disease
- Severe obesity (defined as a BMI >35 kg/m2)
- Known history of hypersensitivity to β-lactams and imidazoles
- Preoperative severe impairment in renal function (creatinine clearance (MDRD) < 30 ml/min)
- Patients with known colonization with multidrug-resistant digestive bacteria, especially multidrug-resistant gram-negative bacteria (requiring specific infection control measures)
- Allergy to lactose, galactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorption (rare metabolic disease)
- Pregnant women, breastfeeding women, women of childbearing age without effective contraceptive- Refusal to participate or inability to provide informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo Placebo oral antibiotic prophylaxis using ornidazole, which has a spectrum of activity extended to most anaerobic bacteria and whose pharmacokinetic profile allows a single administration the day before surgery, in addition to intravenous antibiotic prophylaxis could be more effective than intravenous antibiotic prophylaxis alone using cephalosporin in reducing the incidence of SSI after elective colorectal surgery. Given the number of patients operated of colorectal surgery each year, the study is of significant clinical importance ornidazole ornidazole oral antibiotic prophylaxis using ornidazole, which has a spectrum of activity extended to most anaerobic bacteria and whose pharmacokinetic profile allows a single administration the day before surgery, in addition to intravenous antibiotic prophylaxis could be more effective than intravenous antibiotic prophylaxis alone using cephalosporin in reducing the incidence of SSI after elective colorectal surgery. Given the number of patients operated of colorectal surgery each year, the study is of significant clinical importance
- Primary Outcome Measures
Name Time Method occurrence of any SSI within 30 days after surgery. 30 days after surgery The primary end point of the trial is the occurrence of any SSI within 30 days after surgery. SSI will be classified as superficial, deep and/or organ-space infection according to validated and well-defined criteria developed by the Centers for Disease Control and Prevention (CDC).
- Secondary Outcome Measures
Name Time Method Number of postoperative complications 30 days after surgery Using the Dindo and Clavien classification
Number of surgical complications: anastomotic leakage and the need for abdominal reoperation and/or radiological intervention 30 days after surgery Incidence of individual types of SSI according to the group of treatment 30 days after surgery Incidence of individual types of SSI (superficial incision infection, deep incision infection and organ-space infection) according to the group of treatment, 30 days after surgery
Duration of hospital stay 30 days after surgery Including hospital stay of patients who are readmitted after surgery
All-cause mortality 90 days after surgery Time to introduction of adjuvant chemotherapy related to SSI 30 days after surgery Postoperative syndrome of systemic inflammatory response (Infectious complications) 30 days after surgery Number of Postoperative syndrome of systemic inflammatory responses, in each group
Sepsis (Infectious complications) 30 days after surgery Number of Sepsis, in each group
Septic shock (Infectious complications) 30 days after surgery Number of Septic shocks, in each group
Arrhythmia (Cardiovascular complications) 30 days after surgery Number of arrhythmias, in each group
Myocardial infarction (Cardiovascular complications) 30 days after surgery Number of myocardial infarctions, in each group
Acute cardiac failure (Cardiovascular complications) 30 days after surgery Number of acute cardiac failures, in each group
Pneumonia (Respiratory complications) 30 days after surgery Number of pneumonias, in each group
Need for postoperative reventilation (Respiratory complications) 30 days after surgery Number of postoperative reventilations (intubation and/or non-invasive mechanical ventilation), in each group
Renal dysfunction 30 days after surgery Number of Renal dysfunctions in each group. Defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification
Time to initiation of adjuvant chemotherapy 30 days after surgery Comparaison of time to initiation of adjuvant chemotherapy between the 2 groups
Need for hospital readmission 30 days after surgery Number of hospital readmissions, in each group
Unexpected admission to intensive care unit 30 days after surgery Number of Unexpected admissions to intensive care unit, in each group
Hospital free days 30 days after surgery
Trial Locations
- Locations (1)
CHU Clermont-Ferrand
🇫🇷Clermont-Ferrand, France