Duration of Postoperative Antibiotic Prophylaxis in Facial Fractures
Primary Purpose
Surgical Wound Infection
Status
Terminated
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Amoxicillin/clavulanic acid
Amoxicillin plus placebo
Sponsored by
About this trial
This is an interventional prevention trial for Surgical Wound Infection focused on measuring Surgical Wound Infection, Facial Injuries, Orbital Fractures, Zygomatic Fractures, Mandibular Fractures, Jaw Injuries
Eligibility Criteria
Inclusion Criteria:
- Isolated orbital fracture, zygomatic fracture, mandibular fracture, or LeFort I/II/III fracture which requires surgical treatment
- Written informed consent obtained
Exclusion Criteria
- Need of intensive care treatment
- Presence of an acute bacterial infection
- Gunshot wounds
- Pathological fracture
- Skull base fracture with rhinoliquorrhea or intracranial emphysema
- History of malignancy or radiation to the head and neck area
- Known hypersensitivity, allergy to penicillin or other beta-lactam antibiotics
- Reduced body weight (<40kg or BMI<17), severe renal insufficiency (stage 4 according to the Kidney Disease Outcomes Quality Initiative (KDOQI))
- Insufficient patient compliance
Sites / Locations
- Dep. of Oral and Maxillofacial Surgery, Bern University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
1
2
Arm Description
Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group 1 then receives amoxicillin/clavulanic acid 625 mg orally every eight hours for four days.
Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group 2 receives oral placebo using the same schedule for the same duration as group 1.
Outcomes
Primary Outcome Measures
Number of patients with infection
Infection according to Surgical site infection by CDC
Secondary Outcome Measures
Number of patients with infection
Infection according to Surgical site infection by CDC
Number of patients with infection
Infection according to Surgical site infection by CDC
Number of patients with infection
Infection according to Surgical site infection by CDC
Number of patients with infection
Infection according to Surgical site infection by CDC
Number of patients with infection
Infection according to Surgical site infection by CDC
Number of days between trauma and first antibiotic administration
Number of days between trauma and operation
Location of fracture
Duration of surgery
Measured in minutes
Number of patients with concomitant injuries
Full Information
NCT ID
NCT01583062
First Posted
April 20, 2012
Last Updated
July 12, 2013
Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
Schweizerische Unfallversicherung SUVA, Switzerland, Mepha Parma AG, Switzerland, GlaxoSmithKline AG, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT01583062
Brief Title
Duration of Postoperative Antibiotic Prophylaxis in Facial Fractures
Official Title
Duration of Postoperative Antibiotic Prophylaxis in Facial Fractures (Mandibular Fractures, Zygomaticoorbital Fractures, Isolated Orbital Blow-out Fractures and LeFort I/II/III Fractures): 1 Day vs. 5 Days: a Prospective, Randomized, Double Blind and Placebo Controlled Study (Phase IV)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Terminated
Why Stopped
Limited number of patients
Study Start Date
January 2006 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
Schweizerische Unfallversicherung SUVA, Switzerland, Mepha Parma AG, Switzerland, GlaxoSmithKline AG, Switzerland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Facial fractures make up a significant proportion of injuries in trauma patients. Treatment of these fractures often results in standard surgical interventions. While up to the early 1980's perioperative antibiotic prophylaxis in maxillofacial surgery was controversial, its efficacy is well accepted today. Chole and his team could show that the administration of antibiotics one hour preoperatively and eight hours after the intervention reduces the incidence of infectious complications in facial fractures from 42,2% to 8.9%. However there is still no consensus about the duration of the postoperative administration. In literature postoperative prophylaxis in facial fractures varies from single-shot 6-7 up to a duration of 7 and even ten days postoperatively 8-10. The use of antibiotics can be associated with allergic or toxic reactions, adverse effects, drug interactions and increasing bacterial resistance. In addition some authors assume that a prolonged administration of antibiotics might increase the risk of infectious complications via superinfection. On the other hand a short term or single shot administration might not be enough to prevent the onset of an postoperative infection. Up to date there is no standard to support the administration of antibiotics after surgical repair of a facial fracture.
The purpose of this prospective, randomized double-blinded trial is to investigate the utility of antibiotics administered in the postoperative period after surgical revision of facial fractures.
Hypothesis: a short-term antibiotic prophylaxis of 1 day postoperatively is equally effective as a long-term administration of 5 days in facial fractures.
Detailed Description
Background
While up to the early 1980's perioperative antibiotic prophylaxis in maxillofacial surgery was controversial its efficacy is well accepted today. Chole et al. showed that the administration of antibiotics reduces the incidence of infectious complications in facial fractures from 42,2% to 8.9%.
However there is still no consensus about the duration of the postoperative administration. In literature postoperative prophylaxis varies from single-shot up to 7 and even ten days postoperatively.
Antibiotic use is costly and associated with allergic reactions, toxic reactions, adverse effects, drug interactions and increasing bacterial resistance. Additionally some authors assume that a prolonged administration of antibiotics might even increase the risk of infectious complications via superinfection. On the other hand one might risk an increase of postoperative infections with a short term or single shot administration.
In a medline search only few studies could be found which deal with antimicrobial prophylaxis in maxillofacial surgery and in facial trauma surgery in particular.
Articles which advocate a single shot administration contain a very inhomogeneous group of patients. Merten et al. compared a single shot with a 48h regimen. The study included cleft patients, tumor resections, dental surgery, sinus revisions, plastic surgery and trauma. He concluded that a one shot administration of 1500mg cefuroxime is equally effective as a 48h regimen.
The second study which investigated the efficacy of single-dose antibiotic prophylaxis included preprosthetic, plastic, orthognathic, tumor and trauma surgery. Here also single shot administration was found to be sufficient in preventing postoperative infection. Studies about antibiotic single shot administration which included trauma patients only do not exist.
Some studies compared a 12 or 24 hour with a 5 day postoperative regime: Johnson et al. conducted a study with one hundred nine patients requiring pedicled flap reconstruction in the region of the head and neck. He investigated if 5 days of antibiotic administration would be more effective than 1 day and concluded that no beneficial effect from administration of antibiotics for longer than 24 hours postoperatively can be achieved in patients who undergo myocutaneous flap reconstruction.
Bentley et al. studied the effect on infection rates of 1-day and 5-day administration of prophylactic antibiotics in orthognathic surgical procedures. He concluded that antibiotic prophylaxis for orthognathic surgical procedures should continue beyond the immediate postoperative period for 5 days since the infection rate was significantly higher in the one day regimen (60% vs. 6.7%). It must be stated that in this study very strict criteria for wound infection (such as spontaneous wound dehiscence in the absence of pus drainage) were applied.
Abubaker et al. evaluated the difference between the effect of a 5-day postoperative course and a 12 hour administration of antibiotics in 30 Patients on the incidence of postoperative infection in uncomplicated fractures of the mandible. He concluded that a prolonged administration of antibiotics has no benefit in reducing the incidence of infections.
In other surgical fields guidelines concerning the perioperative antibiotic use have been established. The East practice management guidelines for example recommend to limit the postoperative administration in open fractures to 48 hours after wound closure. Unfortunately these guidelines can not be uncritically applied to maxillofacial trauma patients out of several reasons. Not only the fracture patterns are basically different from those in orthopedics but also the surgical treatment differs in many aspects: the impossibility of complete wound disinfection, the continuing contamination by saliva even after primary closure, the lack of casts or sterile wound dressings, the impossibility of extensive wound debridement or open wound treatment.
Pharmaceutical study substance:
Co-amoxiclav is an antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the ß-lactamase inhibitor, clavulanate potassium. It was introduced as "Augmentin®" in 1984 by Glaxosmithkline and Smithkline Beecham (collectively "GSK"). Since the patent expired in december 2002 several generic versions were approved.
It is used in the treatment of lower respiratory, middle ear, sinus, skin and urinary tract infections. In ENT and maxillofacial surgery it is used for prophylaxis and therapy for several indications. In the investigators' department the present prophylaxis regimen for facial fractures varies from 5 to 8 days postoperatively.
Objective
Aim of this study is to evaluate the difference between the effect of a five- vs. a one-day postoperative course of antibiotics on the incidence of postoperative infections in facial fractures.
Methods
Patients with a facial fractures, which need surgical revision, are randomly assigned into two groups. Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group A then receives amoxicillin/clavulanic acid 625 mg orally every eight hours for four days. Group B receives oral placebo using the same schedule for the same duration as group A. Follow up appointments are 1, 2, 4, 6 and 12 weeks and 6 months after surgery. The developement of a surgical site infection (according to CDC) is defined as primary end point.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Wound Infection
Keywords
Surgical Wound Infection, Facial Injuries, Orbital Fractures, Zygomatic Fractures, Mandibular Fractures, Jaw Injuries
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
217 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group 1 then receives amoxicillin/clavulanic acid 625 mg orally every eight hours for four days.
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group 2 receives oral placebo using the same schedule for the same duration as group 1.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin/clavulanic acid
Intervention Description
Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group 1 then receives amoxicillin/clavulanic acid 625 mg orally every eight hours for four days.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin plus placebo
Intervention Description
Both groups receive amoxicillin/clavulanic acid 1.2 g intravenously every eight hours from admission up to 24 hours postoperatively. Group 2 receives oral placebo using the same schedule for the same duration as group 1.
Primary Outcome Measure Information:
Title
Number of patients with infection
Description
Infection according to Surgical site infection by CDC
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of patients with infection
Description
Infection according to Surgical site infection by CDC
Time Frame
1 week
Title
Number of patients with infection
Description
Infection according to Surgical site infection by CDC
Time Frame
2 weeks
Title
Number of patients with infection
Description
Infection according to Surgical site infection by CDC
Time Frame
4 weeks
Title
Number of patients with infection
Description
Infection according to Surgical site infection by CDC
Time Frame
6 weeks
Title
Number of patients with infection
Description
Infection according to Surgical site infection by CDC
Time Frame
12 weeks
Title
Number of days between trauma and first antibiotic administration
Time Frame
at dismissal from hospital, expected to be after 5 days
Title
Number of days between trauma and operation
Time Frame
At dismissal from hospital, expected to be after 5 days
Title
Location of fracture
Time Frame
At the end of surgery, expected to be after 90 minutes
Title
Duration of surgery
Description
Measured in minutes
Time Frame
At the end of surgery, expected to be after 90 minutes
Title
Number of patients with concomitant injuries
Time Frame
At the end of surgery, expected to be after 90 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Isolated orbital fracture, zygomatic fracture, mandibular fracture, or LeFort I/II/III fracture which requires surgical treatment
Written informed consent obtained
Exclusion Criteria
Need of intensive care treatment
Presence of an acute bacterial infection
Gunshot wounds
Pathological fracture
Skull base fracture with rhinoliquorrhea or intracranial emphysema
History of malignancy or radiation to the head and neck area
Known hypersensitivity, allergy to penicillin or other beta-lactam antibiotics
Reduced body weight (<40kg or BMI<17), severe renal insufficiency (stage 4 according to the Kidney Disease Outcomes Quality Initiative (KDOQI))
Insufficient patient compliance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Lieger, MD, DMD
Organizational Affiliation
Department of Oral and Maxillofacial Surgery, University Hospital Bern, Bern, Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tateyuki Iizuka, MD, DDS, PhD
Organizational Affiliation
Department of Oral and Maxillofacial Surgery, University Hospital Bern, Bern, Switzerland
Official's Role
Study Chair
Facility Information:
Facility Name
Dep. of Oral and Maxillofacial Surgery, Bern University Hospital
City
Bern
ZIP/Postal Code
CH-3011
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
1069110
Citation
Peterson LJ, Booth DF. Efficacy of antibiotic prophylaxis in intraoral orthognathic surgery. J Oral Surg. 1976 Dec;34(12):1088-91.
Results Reference
background
PubMed Identifier
6439657
Citation
Martis C, Karabouta I. Infection after orthognathic surgery, with and without preventive antibiotics. Int J Oral Surg. 1984 Dec;13(6):490-4. doi: 10.1016/s0300-9785(84)80019-8.
Results Reference
background
PubMed Identifier
1063838
Citation
Yrastorza JA. Indications for antibiotics in orthognathic surgery. J Oral Surg. 1976 Jun;34(6):514-6.
Results Reference
background
PubMed Identifier
3304348
Citation
Chole RA, Yee J. Antibiotic prophylaxis for facial fractures. A prospective, randomized clinical trial. Arch Otolaryngol Head Neck Surg. 1987 Oct;113(10):1055-7. doi: 10.1001/archotol.1987.01860100033016.
Results Reference
background
PubMed Identifier
8306818
Citation
Hotz G, Novotny-Lenhard J, Kinzig M, Soergel F. Single-dose antibiotic prophylaxis in maxillofacial surgery. Chemotherapy. 1994 Jan-Feb;40(1):65-9. doi: 10.1159/000239173.
Results Reference
background
PubMed Identifier
8314293
Citation
Merten HA, Halling F. [Perioperative antibiotic prophylaxis in maxillofacial surgery]. Infection. 1993;21 Suppl 1:S45-8. doi: 10.1007/BF01710343. German.
Results Reference
background
PubMed Identifier
11732026
Citation
Abubaker AO, Rollert MK. Postoperative antibiotic prophylaxis in mandibular fractures: A preliminary randomized, double-blind, and placebo-controlled clinical study. J Oral Maxillofac Surg. 2001 Dec;59(12):1415-9. doi: 10.1053/joms.2001.28272.
Results Reference
background
PubMed Identifier
12966479
Citation
Folkestad L, Granstrom G. A prospective study of orbital fracture sequelae after change of surgical routines. J Oral Maxillofac Surg. 2003 Sep;61(9):1038-44. doi: 10.1016/s0278-2391(03)00316-1. Erratum In: J Oral Maxillofac Surg. 2003 Nov;61(11):1375.
Results Reference
background
PubMed Identifier
3253045
Citation
Gerlach KL, Pape HD. [Studies on preventive antibiotics in the surgical treatment of mandibular fractures]. Dtsch Z Mund Kiefer Gesichtschir. 1988 Nov-Dec;12(6):497-500. No abstract available. German.
Results Reference
background
PubMed Identifier
11904577
Citation
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available.
Results Reference
background
Links:
URL
http://www.cdc.gov/
Description
Click here for more information about the definition of Surgical Site Infections
Learn more about this trial
Duration of Postoperative Antibiotic Prophylaxis in Facial Fractures
We'll reach out to this number within 24 hrs