Alternative Antibiotic Regime in the Treatment of GAgP

February 9, 2018 updated by: Esra Guzeldemir-Akcakanat, Kocaeli University

Clinical Evaluation of Systemic Moxifloxacin Compared to Amoxicillin Plus Metronidazole Adjunct to Non-surgical Treatment in Generalized Aggressive Periodontitis: A Randomized Clinical Trial

The objective of this randomized clinical study was to evaluate the effect of systemic administration of moxifloxacin compared to amoxicillin plus metronidazole combined with non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in 6-month follow-up.

A total of 40 systemically healthy patients with GAgP will evaluate in this randomized clinical trial. Periodontal parameters (plaque index, gingival index, probing depth, bleeding on probing, clinical attachment level) will be recorded at baseline, 1st, 3rd and 6th month. Patients will receive either 400 mg moxifloxacin per os once daily or 500 mg metronidazole and 500 mg amoxicillin per os three times daily for 7 days consecutively.

Study Overview

Detailed Description

The American Academy of Periodontology and the European Federation of Periodontology were reported that patients with GAgP may have benefit from adjunctive administration of antibiotics. Antibiotics are used as an adjunct to nonsurgical treatment either locally or systemically. Systemic antimicrobial agents as adjunct to nonsurgical treatment provide additional benefits over mechanical therapy alone in terms of probing depth reduction and periodontal attachment gain.

Amoxicillin is a moderate spectrum, bacteriolytic β-lactam antibiotic, and metronidazole which is active against anaerobic bacteria is a nitroimidazole. scaling and root planing combination with metronidazole plus amoxicillin therapy was found to be more effective in suppressing P. gingivalis and eradication of A. actinomycetemcomitans and preventing re-colonization of A. actinomycetemcomitans because of the synergistic effect of this combination and their wide spectrum of activity. It was found to be superior to azithromycin, doxycycline, and metronidazole in the treatment of GAgP.

Quinolones were introduced for use in urinary tract infections in the 1970s. Moxiflocaxin is a fourth generation fluoroquinolone antibiotic exhibits good tissue penetration and high oral bioavailability and has improved activity against Gram- positive, aerobic and anaerobes. Moxifloxacin is used in the systemic treatment of respiratory infections, acute sinusitis, odontogenic abscesses, osteomyelitis of the mandible and locally in the treatment of ophthalmic infections.

Moxiflocaxin has good activity against putative periodontal pathogens, including Porphyromonas gingivalis, Tanneralla forsythia, Prevotella spp, Fusobacterium nucleatum, Actinomyces spp, Campylobacter rectus, Peptostreptococcus spp. and Aggregatibacter actinomycetemcomitans, located within biofilm or intracellulary. It was shown that A.a. strains were highly susceptible to fluoro-quinolones ciprofloxacin and moxifloxacin. Some of the adjunctive antibiotics are secreted in saliva in insufficient concentrations to inhibit A.a. Moxifloxacin seems to be secreted in saliva at higher levels than in plasma and may also concentrate at the site of infection since it penetrates polymorphonuclear granulocytes and epithelial cells. Moxifloxacin was found to be superior to clindamycin, metronidazole or doxycycline.

Systemic administration of moxifloxacin as an adjunct to scaling and root planing was found to be more effective compared to scaling and root planing alone or scaling and root planing in conjunction with doxycycline in the treatment of severe chronic periodontitis. To best our knowledge, there is no study that evaluates the effect of moxifloxacin adjunct to scaling and root planing in the treatment of GAgP.

The aim of this single center, randomized clinical study was to evaluate the impact of adjunctive systemic moxifloxacin compared to the use of adjunctive systemic amoxicillin and metronidazole during full-mouth scaling and root planing on the success of the treatment of patients with GAgP with 6-month follow-up. The hypothesis was the use of adjunctive systemic moxifloxacin would provide the similar clinical results as adjunct systemic amoxicillin and metronidazole during scaling and root planing.

This study was a single-center, randomized, parallel-design clinical trial with 6 month follow-up. It was conducted at Kocaeli University, Faculty of Dentistry, Department of Periodontology between 2011-2013. The study protocol was approved by the Ethics Committee of the Medical Faculty of Kocaeli University (KOU KAEK 5/9) and was conducted in accordance with the Helsinki declaration of 1975, as revised in 2000.

The GAgP patients were recruited from patients seeking periodontal treatment at Kocaeli University, Faculty of Dentistry, Department of Periodontology, Kocaeli, Turkey. Approximately, 12.000 patients were screened the dates between June 2011 and September 2012. A complete medical, dental, periodontal and radiographic examination was performed. The study protocol explained to the patients. From patients who willing to participate to the study, written informed consent was obtained and included the study.

The periodontal diagnosis of subjects with GAgP was established on the basis of clinical and radiographic criteria defined by the 1999 International World Workshop for a Classification of Periodontal Diseases and Conditions. Patients were included if they were between 18 and 35 years of age and otherwise healthy. The bone loss estimation was radiographically performed in each patient for the assessment of the extent and severity of alveolar bone loss. Medical and dental histories were questioned. Subjects were excluded if they had any known systemic diseases or conditions that can/could influence the periodontal status (cancer, cardiovascular and respiratory diseases), history of hepatitis or HIV infection, immunosuppressive chemotherapy, current pregnancy, planning a pregnancy or lactation, requirement for antibiotic prophylaxis, oral diseases other than GAgP, ongoing orthodontic therapy, a history of antibiotic therapy or periodontal treatment within the preceding six months. Subjects were excluded if they had known allergies to quinolones or penicillin or metronidazole.

Periodontal Examination The full-mouth clinical periodontal measurements were recorded at 6 sites per tooth (mesio-buccal, mid-buccal, disto-buccal, disto-lingual, mid-lingual, and mesio-lingual) including plaque index (PI), gingival index (GI), probing depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL). CAL was calculated from the cement-enamel junction to the base of the periodontal pocket. Williams periodontal probe was used for periodontal measurements. All measurements and scaling and root planing were performed by the same single calibrated and trained periodontist in a standardized manner.

Allocation concealment The patients were randomly assigned to one of the study groups. To ensure complete masking of allocation, before the recruitment of the patients, forty identical, opaque-colored, impermeable plastic bags which include toothbrush, interproximal brush, toothpaste and either moxifloxacin or amoxicillin and metronidazole were prepared and coded. A code number was given to each subject. Randomization codes were kept separately from the clinical evaluation forms by one of the authors until the treatment and follow-up visits were completed. The examiner who performed the treatment was unaware of the allocation.

Prior to treatment, all subjects were gone through motivation sessions for oral hygiene.

Following to periodontal measurements, full-mouth supragingival scaling using ultrasonic scaler and polishing were performed, and a toothbrush, toothpaste and an interproximal toothbrush were provided to all subjects. One week later, the patients were examined for plaque accumulation and oral hygiene. The patients who cannot maintain proper oral hygiene were excluded from the study. Only 39 patients fulfilled the qualification criteria for enrollment for the present study.

Subjects were randomly assigned to receive one of the two treatment groups. Moxifloxacin group received scaling and root planing and an adjunctive systemic antibiotic, 400 mg moxifloxacin, once in a day for 7 days and amoxicillin and metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days. The subjects were instructed to take first dose of the antibiotics in the morning of the first session since the microorganisms are organized on the root surface and protected from antimicrobial agents. Scaling and root planing were performed on 2 consecutive days in 24 hours under the local anesthesia. On each day, scaling and root planing were performed in 2 quadrants using ultrasonic scalers and manual instruments . The endpoint of scaling and root planing was a tactile smooth root surface.

The subjects were insistently informed about the intake of the antibiotics properly, and they asked to inform the researches if they needed to take another antibiotics or anti-inflammatory agents for another reason during and following the study for 6 months.

Patients used a 0.2% chlorhexidine digluconate rinse twice a day for a month and brushed their teeth by tooth brushes and interproximal tooth brushes twice a day. Patients asked to report any adverse events and side effects of the antimicrobial agents as soon as possible.

Subjects were monitored one week after the second scaling and root planing session. At this session, antibiotic intake, adverse events and side effects were questioned; oral hygiene and plaque accumulation were controlled. Subjects were screened at 1, 3 and 6 months after completion of nonsurgical treatment. During these sessions, clinical periodontal parameters, any medical history change, especially, whether antibiotic therapy had been prescribed for any reason was recorded. At the end of these sessions, supragingival scaling was performed, if needed.

The present study was conducted within in the same clinic, and the patients were taken to the same dental chair and treated with a same experienced periodontist for to discard discrepancies and to provide standardized and controlled environment.

Sample size calculation

The primary outcome variable was probing depth changes. The sample size was calculated based on previous information from a study conducted in our department, using data relative to the mean difference and standard deviation (SD) between the experimental periods for the probing depth parameters.57 Considering a mean probing depth difference of 1.3 mm between evaluation periods, it was estimated that 13 patients for each group would be necessary to provide 95% power (0.54 SD, α error of 0.05, and β error of 0.2).58 However, we aimed to recruit 20 patients to each group if we lose to follow the patients during the study.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Kocaeli, Turkey, 41190
        • Kocaeli University Faculty of Dentistry Department of Periodontology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The periodontal diagnosis of subjects with GAgP was established on the basis of clinical and radiographic criteria defined by the 1999 International World Workshop for a Classification of Periodontal Diseases and Conditions.
  • Patients were included if they were between 18 and 35 years of age and otherwise healthy.

Exclusion Criteria:

  • if the patients had any known systemic diseases or conditions that can/could influence the periodontal status (cancer, cardiovascular and respiratory diseases)
  • history of hepatitis or HIV infection,
  • immunosuppressive chemotherapy
  • current pregnancy, planning a pregnancy or lactation
  • requirement for antibiotic prophylaxis
  • oral diseases other than GAgP, ongoing orthodontic therapy
  • a history of antibiotic therapy or periodontal treatment within the preceding six months.
  • Subjects were excluded if they had known allergies to quinolones or penicillin or metronidazole
  • Not willing to participate to the study.
  • Not accept to sign written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: amoxicillin+metronidazole
amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.
500 mg, 3 times per day for 7 days
Other Names:
  • largopen
500 mg, 3 times per day, for 7 days
Other Names:
  • flagyl
Experimental: moxifloxacin
The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.
400 mg, once in a day for 7 days.
Other Names:
  • pitoxil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Primary Outcome Variable Was Probing Depth.
Time Frame: 6-months
We measured the probing depth at baseline, 1st, 3rd and 6th months. The changes were evaluated among and between groups.
6-months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Attachment Loss Were Considered as a Secondary Measure.
Time Frame: 6-months
Attachment loss were recorded at baseline, 1st, 3rd and 6th months as millimeters. The data were compared among and between groups.
6-months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Esra Guzeldemir-Akcakanat, Kocaeli University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

August 20, 2014

First Submitted That Met QC Criteria

August 20, 2014

First Posted (Estimate)

August 22, 2014

Study Record Updates

Last Update Posted (Actual)

November 2, 2018

Last Update Submitted That Met QC Criteria

February 9, 2018

Last Verified

February 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Aggressive Periodontitis

Clinical Trials on Amoxicillin

Subscribe