Elective Colorectal SurgeryPhase 3COMBINENCT02618720
Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery
A Phase 3 study testing ornidazole in people with Elective Colorectal Surgery, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Elective Colorectal Surgery
- What is being tested?
- ornidazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 920 participants
- Where
- 1 siteFrance
- Study dates
- 25 May 2016to 30 Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18
- Laparoscopic or non-laparoscopic elective colorectal surgery
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery: A Double-blinded Multicenter Prospective Randomized Controlled Trial
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.
Read the 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:
- prolonged duration of intravenous antibiotic administration, which is no longer recommended in elective surgery;
- the use of antibiotics for oral prophylaxis whose availability is limited;
- only a few studies focused specifically on colorectal resection;
- most studies did not include enhanced recovery after surgery (ERAS) programs, which was found to improve outcome following colorectal surgery, and
- 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
- Conditions
- Elective Colorectal Surgery
- Being tested
- ornidazole, Placebo
- Keywords
- Antimicrobial prophylaxis, Colorectal surgery, Surgical Site Infection, Postoperative morbidity
- Medical subject headings
- Surgical Wound Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ornidazoleDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| ornidazole | Experimental | 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 Receives: Drug: ornidazole |
| placebo | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
occurrence of any SSI within 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).
Measured: 30 days after surgery
Secondary outcomes (20)
Incidence of individual types of SSI according to the group of treatment
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
Measured: 30 days after surgery
Number of postoperative complications
Using the Dindo and Clavien classification
Measured: 30 days after surgery
Number of surgical complications: anastomotic leakage and the need for abdominal reoperation and/or radiological intervention
Measured: 30 days after surgery
Duration of hospital stay
Including hospital stay of patients who are readmitted after surgery
Measured: 30 days after surgery
All-cause mortality
Measured: 30 days after surgery
All-cause mortality
Measured: 90 days after surgery
Time to introduction of adjuvant chemotherapy related to SSI
Measured: 30 days after surgery
Postoperative syndrome of systemic inflammatory response (Infectious complications)
Number of Postoperative syndrome of systemic inflammatory responses, in each group
Measured: 30 days after surgery
Sepsis (Infectious complications)
Number of Sepsis, in each group
Measured: 30 days after surgery
Septic shock (Infectious complications)
Number of Septic shocks, in each group
Measured: 30 days after surgery
Arrhythmia (Cardiovascular complications)
Number of arrhythmias, in each group
Measured: 30 days after surgery
Myocardial infarction (Cardiovascular complications)
Number of myocardial infarctions, in each group
Measured: 30 days after surgery
Acute cardiac failure (Cardiovascular complications)
Number of acute cardiac failures, in each group
Measured: 30 days after surgery
Pneumonia (Respiratory complications)
Number of pneumonias, in each group
Measured: 30 days after surgery
Need for postoperative reventilation (Respiratory complications)
Number of postoperative reventilations (intubation and/or non-invasive mechanical ventilation), in each group
Measured: 30 days after surgery
Renal dysfunction
Number of Renal dysfunctions in each group. Defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification
Measured: 30 days after surgery
Time to initiation of adjuvant chemotherapy
Comparaison of time to initiation of adjuvant chemotherapy between the 2 groups
Measured: 30 days after surgery
Need for hospital readmission
Number of hospital readmissions, in each group
Measured: 30 days after surgery
Unexpected admission to intensive care unit
Number of Unexpected admissions to intensive care unit, in each group
Measured: 30 days after surgery
Hospital free days
Measured: 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2015 (estimated)
- Study start25 May 2016
- Primary completion26 Nov 2019
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Elective Colorectal SurgeryStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 920 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02618720
- Sponsor's protocol ID
- CHU-0250
- Other IDs
- 2015-002559-84, 2015
- Acronym
- COMBINE
- Status last verified
- Apr 2026
- First submitted
- 5 Nov 2015
- Last updated
- 21 Apr 2026
- Results posted
- No
Publications
Futier E, Jaber S, Garot M, Vignaud M, Panis Y, Slim K, Lucet JC, Lebuffe G, Ouattara A, El Amine Y, Couderc P, Dupre A, De Jong A, Lasocki S, Leone M, Pottecher J, Pereira B, Paugam-Burtz C; COMBINE study group. Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial. BMJ. 2022 Nov 3;379:e071476. doi: 10.1136/bmj-2022-071476.
PubMed 36328372Willis MA, Toews I, Soltau SL, Kalff JC, Meerpohl JJ, Vilz TO. Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery. Cochrane Database Syst Rev. 2023 Feb 7;2(2):CD014909. doi: 10.1002/14651858.CD014909.pub2.
PubMed 36748942Vignaud M, Paugam-Burtz C, Garot M, Jaber S, Slim K, Panis Y, Lucet JC, Bourdier J, Morand D, Pereira B, Futier E; COMBINE trial management committee. Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial. BMJ Open. 2018 Apr 12;8(4):e020254. doi: 10.1136/bmjopen-2017-020254.
PubMed 29654027
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery: A Double-blinded Multicenter Prospective Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02618720
- Acronym / sponsor ID
- COMBINE / CHU-0250
- Conditions
- Elective Colorectal Surgery
- Keywords
- Antimicrobial prophylaxis, Colorectal surgery, Surgical Site Infection, Postoperative morbidity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 920 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 25 May 2016 (actual)
- Primary completion
- 26 Nov 2019 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 1 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- prolonged duration of intravenous antibiotic administration, which is no longer recommended in elective surgery;
- the use of antibiotics for oral prophylaxis whose availability is limited;
- only a few studies focused specifically on colorectal resection;
- most studies did not include enhanced recovery after surgery (ERAS) programs, which was found to improve outcome following colorectal surgery, and
- 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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ornidazole | Experimental | Drug: ornidazoleoral 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 |
| placebo | Placebo comparator | Drug: Placebooral 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age > 18
- Laparoscopic or non-laparoscopic elective colorectal surgery
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ornidazole | Drug | ornidazole |
| Placebo | Drug | placebo |
Primary outcome
occurrence of any SSI within 30 days after surgery.
Time frame: 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).
20 secondary outcomes
Incidence of individual types of SSI according to the group of treatment
Time frame: 30 days after surgery
Number of postoperative complications
Time frame: 30 days after surgery
Number of surgical complications: anastomotic leakage and the need for abdominal reoperation and/or radiological intervention
Time frame: 30 days after surgery
Duration of hospital stay
Time frame: 30 days after surgery
All-cause mortality
Time frame: 30 days after surgery
All-cause mortality
Time frame: 90 days after surgery
Time to introduction of adjuvant chemotherapy related to SSI
Time frame: 30 days after surgery
Postoperative syndrome of systemic inflammatory response (Infectious complications)
Time frame: 30 days after surgery
Sepsis (Infectious complications)
Time frame: 30 days after surgery
Septic shock (Infectious complications)
Time frame: 30 days after surgery
Arrhythmia (Cardiovascular complications)
Time frame: 30 days after surgery
Myocardial infarction (Cardiovascular complications)
Time frame: 30 days after surgery
Acute cardiac failure (Cardiovascular complications)
Time frame: 30 days after surgery
Pneumonia (Respiratory complications)
Time frame: 30 days after surgery
Need for postoperative reventilation (Respiratory complications)
Time frame: 30 days after surgery
Renal dysfunction
Time frame: 30 days after surgery
Time to initiation of adjuvant chemotherapy
Time frame: 30 days after surgery
Need for hospital readmission
Time frame: 30 days after surgery
Unexpected admission to intensive care unit
Time frame: 30 days after surgery
Hospital free days
Time frame: 30 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Results publication: PubMed 36328372Futier E, Jaber S, Garot M, Vignaud M, Panis Y, Slim K, Lucet JC, Lebuffe G, Ouattara A, El Amine Y, Couderc P, Dupre A, De Jong A, Lasocki S, Leone M, Pottecher J, Pereira B, Paugam-Burtz C; COMBINE study group. Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial. BMJ. 2022 Nov 3;379:e071476. doi: 10.1136/bmj-2022-071476.
- Derived from this study: PubMed 36748942Willis MA, Toews I, Soltau SL, Kalff JC, Meerpohl JJ, Vilz TO. Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery. Cochrane Database Syst Rev. 2023 Feb 7;2(2):CD014909. doi: 10.1002/14651858.CD014909.pub2.
- Derived from this study: PubMed 29654027Vignaud M, Paugam-Burtz C, Garot M, Jaber S, Slim K, Panis Y, Lucet JC, Bourdier J, Morand D, Pereira B, Futier E; COMBINE trial management committee. Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial. BMJ Open. 2018 Apr 12;8(4):e020254. doi: 10.1136/bmjopen-2017-020254.
Related trials for Elective Colorectal Surgery
Not yet recruiting
Nurse-Led Prehabilitation Before Major Abdominal Cancer Surgery
Colorectal Cancer
Not yet recruiting
Bioelectrical Response to Preoperative Hydration in Colorectal Surgery
Postoperative Complications
Recruiting
Oral Antibiotics vs. No Antibiotics in Pediatric Colorectal Surgery
Bowel Cleansing Prior to Clinical Procedures, Colorectal Anastomosis
Not yet recruitingPhase 4
Transversus Abdominis Plane and Rectus Sheath Block for Robotic Colectomy
Rectus Sheath Block, Transversus Abdominis Plane Block
Recruiting
Pre-Surgical Immunonutrition's Effect on Colorectal Surgery
Colorectal Surgery
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ornidazole in people with Elective Colorectal Surgery, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
occurrence of any SSI within 30 days after surgery. (time frame: 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02618720, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.