Clinical trial NCT02764710: Randomized Controlled Trial Comparing Long and Short Duration of Antibiotic Prophylaxis for Patients Undergoing Sinus Lift Surgery
Official title: Randomized Controlled Trial Comparing Long and Short Duration of Antibiotic Prophylaxis for Patients Undergoing Sinus Lift Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Maxillofacial Surgery
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2016-05-06
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The optimal use of prophylactic antibiotic therapy to prevent infection after sinus lift and augmentation surgery is unknown. This is a comparative open label interventional trial comparing a standard 7-day course of postoperative treatment with amoxicillin-clavulanate with short antibiotic treatment for up to 24 hours postoperatively. The primary study outcome is the postoperative surgical site infection in the standard versus the short treatment arms. Secondary outcomes are drug-related adverse events and Clostridium difficile infection.

Detailed description: Research rational

The use of antibiotics as prophylaxis for surgical site infection (SSI) is well based in most fields of surgery. The use of prophylactic antibiotics can reduce the rate of post-surgical infections substantially. Nonetheless, overuse of these drugs is likely to expose patients to adverse effects, increase the rate of microbial drug resistance and lead to unnecessary expenses.

In the field of dentistry there are recommendations for prevention of infective endocarditis. The use of antibiotics for SSI in the field of oral and maxillofacial surgery is not well established, with inconsistent and even contradictory recommendations.

Sinus floor lift and augmentation is a common surgical procedure in modern dentistry. It aims to increase the amount of bone in the posterior maxilla, in the area of the premolar and molar teeth, prior to placement of dental implants. The procedure is performed in a per-oral approach; a mucoperiosteal flap is elevated, the lateral boney wall of the sinus is exposed and a window is cut with a surgical bur. The Schneiderian membrane (sinus periost) is separated and lifted from the bone and a bone graft material is placed into the newly created space. The graft material used can be an autograft, an allograft, a xenograft, an alloplast or a combination of these materials.

The rate of post-operative infection after a sinus lift procedure reaches 7%. An evidence based approach for antibiotic prophylaxis for this procedure does not exist. The standard of care is based on clinical experience and protocols for placing dental implants in the jaws bone.

The current protocols include broad spectrum antibiotics aimed at oral bacteria and main pathogens in acute bacterial sinusitis (Streptoccocus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae): amoxicillin+clavulanic acid or clindamycin / clarithromycin+metronidazole for patients with penicillin allergy. According to the common protocol, the antibiotics are given one day prior to surgery or at the day of surgery (one hour before the first cut) and are continued for seven days post-operatively. This practice contradicts the current recommendation for a shortened postoperative course of antimicrobials for less than 24 hours (10). No evidence suggests that prescribing antibiotics beyond 24 hours lowers the rate of SSI. On the other hand, a prolonged prophylactic regimen elevates the risk of Clostridium difficile infection and contributes to antibiotic resistance.

Lindenboom and Van den Akker have demonstrated in 2003 that not administrating prophylactic antibiotics at all prior to bone augmentation elevates the rate of SSI significantly in comparison with a patient who receives antibiotics. On the other hand, our clinical experience shows that short term prophylactic antibiotics (up to 3 days post-operatively) in sinus augmentation surgery and other bone augmentations in the oral cavity do not elevate the risk of SSI. The need to prescribe antibiotics for more than 24 hours post-operatively was never evaluated in a clinical trial.

In the current trial we will test the hypothesis that a short prophylactic regimen does not differ from a prolonged one. On the contrary, we hypothesize that the adverse effects rate will be lower in patients that will receive antibiotics for a short period.

Aim of the study

This is a prospective randomized non-blinded trial which compares a short prophylactic regimen (till on day post-operatively) with a long prophylactic regimen (till seven days post-operatively as acceptable currently) in patients that undergo sinus augmentation surgery.

Study hypothesis: both groups will display similar rates of SSIs.

Materials and methods

The participants will be recruited from patients in Tel-Aviv Medical Center dental clinic that are in need for a unilateral or bilateral sinus augmentation surgery.

The recruited patients will meet the chief investigator for a thorough explanation on the trial, emphasizing the fact that the surgery itself is not the essence of this trial. After signing an informed consent for participating in the trial, the patients will be randomly split into two groups. The recruited patients will receive a prescription for antibiotics and how to take them: amoxicillin-clavulanate 875mg twice a day starting at the morning of surgery. Patient with penicillin allergy will receive a loading dose of clindamycin 300mg, followed by 150mg every 6 hours. The duration of treatment (one day or seven days post-operatively) will be determined according to the group attribution.

The sinus augmentation surgeries will be performed by the attending surgeons at the Oral and Maxillofacial department, according to a unified protocol: a pre-op chlorhexidine 2% rinse, local anesthesia with Lidocaine 2% with adrenalin 1:100000, elevation of a mucoperiosteal flap to expose the lateral wall of the sinus, performing an access window in the bony wall and lifting the sinus membrane, augmentation of the cavity using a xenogeneic and /or allogeneic bone graft substitute and a collagen membrane, placement of dental implants if feasible and suturing of the flap.

Augmenting the cavity with different materials reflects the common practice and based on the fact that these differences do not alter the rate of post-operative complications or dental implants failure in sinus augmentation sites.

Further treatment with dexamethasone, decongestants and pain medications will be administered according to current protocols and are subject to the surgeon's judgment in order to reflect the common practice.

The patients will be evaluated at the following appointed times until the placement/exposure of the dental implants: one week, two weeks, one month, two months, six months. These dates are part of the standard of care as a follow-up after sinus augmentation surgery.

Patients will be withdrawn from the study if they will not attend the follow-up appointments.

Eligibility criteria: Inclusion Criteria:

1. Adult patient (18 years of age or older) that requires a unilateral or bilateral sinus augmentation surgery.
2. Weight \<150 kg.

Exclusion Criteria:

1. Need for prophylactic antibiotics for infective endocarditis.
2. Chronic antibiotics therapy.
3. Special populations: pregnant women, minors and legally incompetent patients.
4. Patients receiving anticoagulants.
5. Non-balanced diabetes mellitus.
6. Immune-suppression: corticosteroids treatment equivalent to 15mg prednisone for at least 14 days in the past month; chemotherapy, TNF inhibitor or drugs that suppress T-cell activity during the past 90 days; HIV infection.
7. Pathology of the maxillary sinus.
8. History of chronic sinusitis.
9. Patients that underwent a Caldwell-Luc procedure.
10. Patients with residual teeth roots at the planned surgical site.
11. A known state of carriage of Methicillin resistant Staphylococcus aureus or Clostridium difficile in the past year.

Primary outcomes:
measure: Surgical site infection rate
timeFrame: 30 days
Secondary outcomes:
measure: Diarrhea
timeFrame: 30 days
measure: Clostridium difficile infection
timeFrame: 30 days
measure: Adverse event rate
timeFrame: 30 days
Other outcomes:
Locations:
Study officials:
References:
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