Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT01823523 |
| Other study ID # |
ACOMFS-Orthognathic |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
March 29, 2013 |
| Last updated |
January 12, 2015 |
| Start date |
June 2013 |
| Est. completion date |
October 2015 |
Study information
| Verified date |
January 2015 |
| Source |
Atlantic Center for Oral and Maxillofacial Surgery |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Canada: Ethics Review Committee |
| Study type |
Interventional
|
Clinical Trial Summary
Currently there is debate in the literature as to the recommended length of postoperative
antibiotics in patients undergoing orthognathic surgery. The investigators plan to
investigate using a randomized controlled trial the comparison between a 1 day and 3 day
regimen of antibiotics and the effects on post operative infection.
Description:
Capital Health Research Ethics Board Orthognathic Surgery and Postoperative Antibiotic Use
Protocol
Background, Rationale and Statement of Research Question(s):
Surgical site infection is a potential problem with any surgical procedure. Surgical
procedures done through the oral cavity are at a higher risk due to the presence of
bacterial pathogens. Orthognathic surgery, involves incising through oral mucosa and
creating osteotomies in underlying bony structures. Of the potential complications that can
arise from this surgery, post operative infection (POI) is the most common. POI can have a
significant impact on surgical outcomes and are associated with an increased cost to the
health care system. The literature is quite clear on the benefits of presurgical
prophylactic antibiotics in reducing the rate of post operative surgical site infections.1
Currently there is conflicting literature as to the recommended length patients should
receive antibiotics during the postoperative course, and the majority of studies have small
sample sizes.2,3
Orthognathic surgery is considered a clean-contaminated surgery with a suspected POI rate of
10-15%.2 In 1999 Bentley et. al conducted a randomized control trial comparing 1day vs 5day
regimen of antibiotics following orthognathic surgery.4 This trial was stopped due to the
drastic difference seen between the two groups, 6.7% in the 5 day course compared with 60%
seen in the 1 day group.4 This data varies greatly from the rates of infection that the
investigators have seen in their department using a 1 day course of antibiotics. Chow et al.
in 2007 did a retrospective chart review of complications seen in orthognathic surgery. They
found the rate of infection was significantly decreased by continuing antibiotics in the
post operative course when compared to using only one prophylactic dose. They found the
infection rates to be 17.3% with a single preoperative IV dose, 5.1% with a pre-operative
dose and 2 days post-operative, and 7.7% with a pre-operative dose and 3 days of
post-operative antibiotics.5 They also found no significant difference in rates of infection
comparing 2 days and up to 14 days.5 A meta-analysis by Danda et al. in 2011 found that a
regimen consisting of a single dose of preoperative antibiotics followed with an extended
term postoperatively is the most effective in decreasing surgical site infections. They
found the incidence decreased by 3.2 times, with the greatest effect noted with
administration for 2 days.2 Even in this meta-analysis the average number of patients in
each of the 8 studies was 67, with the total number of patients included being 532.2 This
shows the need for randomized controlled studies with large sample sizes in order to
determine the best antimicrobial regimen for these patients. The majority of studies
investigating the rates of infection in orthognathic surgery use penicillin as the
antibiotic of choice due to its spectrum of coverage for oral microbes and it is reasonably
tolerated by patients.2,4-8 In the investigators department cefazolin is the antibiotic of
choice and lower rates of infection have been observed compared to penicillin. The
investigators suspect the lower rates of infection with cefazolin is due to the increased
gram negative coverage and better resistance to beta lactamases. This has influenced the
investigators decision to use first generation cephalosporins instead of penicillin as first
line antimicrobials. In patients allergic to penicillin, clindamycin is used. The criteria
for diagnosis of infection will follow the CDC guidelines for SSI. The primary outcome is to
determine if there is any benefit to extending antimicrobials in the postoperative course
following orthognathic surgery. Secondary outcomes include comparing the rates of infection
between cefazolin/cephalexin groups and the clindamycin groups, and the rate of infection
with different surgical procedures.
Currently at the CDHA the standard perioperative antimicrobial regimen for orthognathic
surgery patients is one preoperative prophylactic dose of 2g of IV cefazolin followed by 1g
IV every 8 hrs for 3 doses. Patients with an allergy to penicillin receive one preoperative
prophylactic dose of IV Clindamycin 600mg, followed by 600mg IV every 8 hrs for 3 doses.
The investigators plan to conduct a double blind randomized controlled trial comparing the
effect of a single day of post operative antibiotics with an extended 3 day course of
antimicrobials on the infection rate. Both groups will receive an IV prophylactic dose
followed by 3 IV doses postoperatively. Group 1 will then receive PO antibiotics for 2
subsequent days following IV treatment, and group 2 will receive a PO placebo.
A placebo will be used in order to blind the two groups so that the patient, surgeon and
investigators are not aware of which patients are receiving the extended regimen of
antibiotics. This will avoid potential bias in the patient report of symptoms or side
effects, and the surgeon's bias in diagnosis of surgical site infection.
Subject Selection:
All patients over the age of 16 years undergoing orthognathic surgery at the QEII VG
hospital are eligible to participate in the study. All surgeons operating at the VG site
have been asked to include their patients in this study. These include patients undergoing
either isolated Lefort I osteotomy, bilateral sagittal split osteotomies, functional
genioplasties, or any combination of the three procedures. Wisdom teeth, if present, will
also be extracted at the time of the surgery. Exclusion criteria include use of antibiotics
in the past 2 weeks, active oral or odontogenic infection, significant medical condition, or
if the patient is immunocompromised. All patients will have history and physical
examination, CBC, INR/PTT, electrolytes as well as a radiographic evaluation prior to
surgery. A power analysis was done to determine the required patient sample size for this
study. This was done using a 5% change in infection as clinically significant and type I
error of 0.05 with 0.90 power. The sample size required would be 397 patients. The
investigators would like to enroll as many as possible over the next 2 years and anticipate
to enroll approximately 500 patients. Study enrollment will finish in 2 years time from
starting date, unless required sample size has not been met at which time it may be decided
to extend length.
Research Plan:
All patients enrolled in the study will receive the standard preoperative IV prophylactic
antibiotic, followed by 3 IV doses postoperatively. The patients will be randomly allocated
to either the placebo or the antibiotic group at their presurgical assessment appointment.
This allocation will be done by a clinical nurse, patients will be given a study patient
number and handed a envelope from a folder that has been mixed sufficiently, inside this
envelope will be a paper with an A or B denoting to the Shoppers Drug Mart pharmacy on the
main floor of the VG hospital to dispense the according bottle they are to receive. This
will be recorded beside their study number, and not be unblinded until the study is
concluded. Blinding is important to avoid bias in assessment of infection by the surgeons,
and to avoid bias in reporting of symptoms of either infection or side effects from the
antibiotics. Following the completion of the IV antibiotic regimen, group 1 will receive
oral cephalexin or clindamycin four times per day for 2 days and group 2 will receive a
placebo four times per day for 2 days. All patients will also be sent home with specific
oral hygiene instructions in addition to chlorhexidine 0.12% rinse to be used for 2 weeks
postoperatively.
Patients will be assessed for signs of infection and recovery progress daily during hospital
stay and during regular recall visits at 2 weeks and 4 weeks following discharge. There is
no additional time requirements or cost to the patient by participating in this study. The
diagnosis of infection will be made according to the CDC criteria of surgical site infection
which include: purulent drainage, wound culture for known pathogen, at least one of signs or
symptoms of infection (pain, tenderness, localized swelling, redness or heat)1.
The patient may withdrawl from the study at any time. A patient may be removed from the
study if there is a significant change in the patients medical condition. An interm review
of the rates of infection will be done and if the data demonstrates an increase risk to
patients participating in study, the study will be stopped and unblinded.
All adverse events, serious adverse events, adverse drug reations will be reported to the
Oral Maxillofacial Surgery Department and the patient will be assessed by the resident or
attending surgeon.
Analysis of Data
All of the data will be organized and pooled according to each specific group. Following the
study the blinding will be undone, and the primary outcome investigating the rate of
infection will be analyzed in each of the four groups, 1 day cefazolin, 3 day
cefazolin/cephalexin, 1 day clindamycin, 3 day clindamycin. Each of the 1 day groups will be
compared and the 3 day groups in order to determine if the length of time on antibiotic has
an effect on the rate of infection. Then the 1 day group and 3 day groups will be compared
for the different type of antibiotic to see if the type of antibiotic has bearing on the
length required. These comparisons will be done using a chi squared formula to look for
statistical significance. This analysis will also be used to compare rates of infection
between the type of surgical procedures done. Each of the groups will also be analyzed for
possible confounding factors including time of surgery, age, sex, and oral hygiene status.
Confidentiality
All data will be kept secure by the research team by storing it in a locked office filing
cabinet, or on a password protected file on the secured hospital network. Only the
investigators, and research nurse will have access to this data. Following the study, the
data will be kept in a locked cabinet for at least 25 years as required by law.
Harms
As all patients will receive the standard current protocol used at the investigators center,
with the test group receiving an addition 2 days of antibiotics. The risks associated with
participation in the study are those seen from prolonged antibiotic use. These include
allergic reactions ranging from rash to anaphylaxis, toxic reactions to kidney, liver,
gastrointestinal and secondary infections from candida or resistant pathogens. If
anaphylaxis occurs normal protocol will be followed for treatment and monitoring. In the
event of other adverse events from the antibiotic it will be stopped and any secondary
infections will be treated appropriately. In the case of post operative infection this will
be treated with a 10 day course of appropriate antibiotics.
Benefits
Overall the benefit of this study is to determine the ideal length of postoperative
antibiotics in preventing post operative surgical site infections in patients undergoing
orthognathic surgery. The group receiving an extended course of antibiotics potentially may
have a lower rate of infection. Conversely, the placebo group may have the same rate of
infection and avoid potential side effects of extended antibiotic treatment.
Disclosure of Any Financial Compensation
There will be no monetary compensation for participation in this study. Either the
antibiotic or the placebo will be provided to the patient at no cost.
References
1. National Center for Infectious Diseases, Mangram AJ, Horan TC, Pearson ML, et. al.
Guideline for Prevention of Surgical Site Infection, 1999. Infection Control and
Hospital Epidemiology, 20:4:247- 278, 1999
2. Danda AK, Ravi P. Effectiveness of Postoperative Antibiotics in Orthognathic Surgery: A
Meta-Analysis. J Oral Maxillofacial Surgery 69:2650-2656,2011
3. Tan SK, Lo J, Zwahlen RA. Perioperative Antibiotic Prophylaxis in Orthognathic Surgery:
A Systematic Review and Meta-Analysis of Clinical Trials. Surg Oral Med Oral Pathology
Oral Radiology Endodontics 112:19-27, 2011
4. Bentley KC, Head TW, Aiello GA. Antibiotic Prophylaxis in Orthognathic Surgery: A 1-Day
Versus 5-Day Regimen. J Oral Maxillofacial Surgery 57:226-230.1999
5. Chow LK, Singh B, et al. Prevalence of Postoperative Complications After Orthognathic
Surgery: A 15year Review. J Oral Maxillofacial Surgery 65:984-992, 2007
6. Ruggles JE, Hann JR, Antibiotic Prophylaxis in Intraoral Orthognathic Surgery. J Oral
Maxillofacial Surgery 42:797-801, 1984.
7. Fridrich KL, Partnoy BE, Zeitler DL. Prospective analysis of Antibiotic Prophylaxis for
Orthognathic Surgery. International Journal Adult Orthodontic and Orthognathic Surgery
9:129-131, 1994
8. Jansisyanont P, Sessirisombat S, Sastravaha P, Bamroong P, Antibiotic Prophylaxis for
Orthognathic Surgery: A Prospective, Comparative, Randomized Study between
Amoxicillin-Clavulanic Acid and Penicillin. J Med Association Thailand 11: 1726-31,
2008.
Advertisements
No advertisements will be used for enrollment in this study.
Additional Considerations
Funding has been provided by the Canadian Association of Oral and Maxillofacial Surgery.
