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Duration of Postoperative Antibiotic Prophylaxis in Facial Fractures

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ClinicalTrials.gov Identifier: NCT01583062
Recruitment Status : Terminated (Limited number of patients)
First Posted : April 23, 2012
Last Update Posted : July 15, 2013
Sponsor:
Collaborators:
Schweizerische Unfallversicherung SUVA, Switzerland
Mepha Parma AG, Switzerland
GlaxoSmithKline AG, Switzerland
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

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.


Condition or disease Intervention/treatment Phase
Surgical Wound Infection Drug: Amoxicillin/clavulanic acid Drug: Amoxicillin plus placebo Phase 4

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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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 217 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : January 2006
Actual Primary Completion Date : November 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 1
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.
Drug: Amoxicillin/clavulanic acid
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.

Placebo Comparator: 2
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.
Drug: Amoxicillin plus placebo
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 Measures :
  1. Number of patients with infection [ Time Frame: 6 months ]
    Infection according to Surgical site infection by CDC


Secondary Outcome Measures :
  1. Number of patients with infection [ Time Frame: 1 week ]
    Infection according to Surgical site infection by CDC

  2. Number of patients with infection [ Time Frame: 2 weeks ]
    Infection according to Surgical site infection by CDC

  3. Number of patients with infection [ Time Frame: 4 weeks ]
    Infection according to Surgical site infection by CDC

  4. Number of patients with infection [ Time Frame: 6 weeks ]
    Infection according to Surgical site infection by CDC

  5. Number of patients with infection [ Time Frame: 12 weeks ]
    Infection according to Surgical site infection by CDC

  6. Number of days between trauma and first antibiotic administration [ Time Frame: at dismissal from hospital, expected to be after 5 days ]
  7. Number of days between trauma and operation [ Time Frame: At dismissal from hospital, expected to be after 5 days ]
  8. Location of fracture [ Time Frame: At the end of surgery, expected to be after 90 minutes ]
  9. Duration of surgery [ Time Frame: At the end of surgery, expected to be after 90 minutes ]
    Measured in minutes

  10. Number of patients with concomitant injuries [ Time Frame: At the end of surgery, expected to be after 90 minutes ]


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01583062


Locations
Switzerland
Dep. of Oral and Maxillofacial Surgery, Bern University Hospital
Bern, Switzerland, CH-3011
Sponsors and Collaborators
University Hospital Inselspital, Berne
Schweizerische Unfallversicherung SUVA, Switzerland
Mepha Parma AG, Switzerland
GlaxoSmithKline AG, Switzerland
Investigators
Principal Investigator: Olivier Lieger, MD, DMD Department of Oral and Maxillofacial Surgery, University Hospital Bern, Bern, Switzerland
Study Chair: Tateyuki Iizuka, MD, DDS, PhD Department of Oral and Maxillofacial Surgery, University Hospital Bern, Bern, Switzerland

Additional Information:
Publications:

Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01583062     History of Changes
Other Study ID Numbers: 235/04
1601 ( Other Identifier: University Hospital Bern )
First Posted: April 23, 2012    Key Record Dates
Last Update Posted: July 15, 2013
Last Verified: July 2013

Keywords provided by University Hospital Inselspital, Berne:
Surgical Wound Infection
Facial Injuries
Orbital Fractures
Zygomatic Fractures
Mandibular Fractures
Jaw Injuries

Additional relevant MeSH terms:
Fractures, Bone
Wound Infection
Surgical Wound
Surgical Wound Infection
Mandibular Fractures
Wounds and Injuries
Infection
Postoperative Complications
Pathologic Processes
Jaw Fractures
Maxillofacial Injuries
Facial Injuries
Craniocerebral Trauma
Trauma, Nervous System
Nervous System Diseases
Skull Fractures
Anti-Bacterial Agents
Amoxicillin
Clavulanic Acids
Clavulanic Acid
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
beta-Lactamase Inhibitors