Efficacy of Amoxicillin-metronidazole Compared to Clindamycin in Patients With Periodontitis and Diabetes

NCT ID: NCT03374176

Last Updated: 2020-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2017-09-30

Brief Summary

Periodontitis is an inflammation of the supporting structures of the teeth, usually caused by specific or groups of microorganisms that results in the progressive destruction of the periodontal ligament and alveolar bone. the objective of periodontitis treatment is to reduce the number of periodontal pathogens. However, there is not an agreement in the use of systemic antibiotics in patients with diabetes. The purpose of the present study was to determine the efficacy of amoxicillin/metronidazole compared to clindamycin during non-surgical treatment of periodontitis in patients with type 2 diabetes mellitus.

Patients and methods In this double-blind, randomized clinical trial, a total of 42 patients with chronic periodontitis and type 2 diabetes were included in a 24-months follow-up. Patients were randomly assigned to treatment with either amoxicillin/metronidazole or clindamycin every for 7 days. Clinical determinations (depth of probing, bleeding at the probe and plaque index) were performed to determine the extent and severity of periodontitis before and after the pharmacological treatment. The intra-group differences were calculated with Wilcoxon rank test. The inter-group differences were calculated with Mann-Whitney test. Sex, bacterial plaque, and bleed to the sounding were summarized using proportions and analyzed with the chi-square method. In all analyses, a P-value of <0.05 (two tailed) was considered statistically significant

Detailed Description

A parallel, randomized, double-blind, active controlled, single center clinical trial was designed to compare the efficacy of two antibiotic therapies with 24-month follow-up. The study protocol was approved by the ethical committee of the Universitary Center of Health Sciences of University of Guadalajara and conducted according to Good Clinical Practice and the principles of the Declaration of Helsinki. All patients provided written informed consent before the initiation of study procedures.

A total of 5 non-study subjects with chronic periodontitis were recruited and used for the calibration exercise. Two designated examiners measured full-mouth probing pockets depths (PPD) for all 5 subjects. On the same day (with a minimum of 15 min separation), the examiner repeated the examination. Upon completion of all measurements, the intra-examiner repeatability for PPD measurement was assessed. The examiner was judged to be reproducible after fulfilling the pre-determined success criteria (the percentage of agreement within 2 mm between repeated measurements had to be at least 70 %). The examiner showed 78.3 % reproducibility.

The sample size was calculated with a 95% confidence level and statistical power of 80 %. A standard deviation of 1.0 mm with an expected difference of 1.0 mm probing pocket depth reduction between treatments. This resulted in a total of 14 patients per arm, however this sample was increased 20% (21 patients per group) to compensate for possible dropouts.

Patient population Criteria for selection Patients of both sexes (aged >18 to 70 years) with a diagnosis of chronic periodontitis according to the 1999 International World Workshop for a Classification of Periodontal Diseases and Conditions and a history of type 2 diabetes with a HbA1C < 8 % and a fasting plasma glucose (FPG) < 180 mg/dL. Patients with aggressive periodontitis, pregnant or lactating females, required antibiotic pre-medication for the performance of periodontal examination and treatment or received antibiotic treatment in the previous 3 months were excluded. A history of anti-inflammatory therapy within preceding six months or that had received a course of periodontal treatment within the last 6 months, allergies to penicillin, metronidazole or clindamycin, and were not able to provide consent to participate in the study were also criteria for exclusion.

Intervention Subjects were randomly allocated 1:1 to receive 500 mg amoxicillin + 250 mg metronidazole or 300 mg clindamycin + placebo using a computer that generated a list of random numbers. Subjects were instructed to take the treatment three times a day for 7 days in both groups.

Assessments During these sessions, a case presentation was given to each subject related to the specific features of his/her disease, as well as a supra- and sub-gingival mechanical debridement was performed. A complete periodontal examination was performed, including a full medical and dental history, an intra-oral examination and a full-mouth periodontal probing. A radiographic examination was undertaken using either periapical x-rays or a ortopantomography.

Clinical parameters Clinical parameters were assessed using a North Caroline Periodontal Probe by the calibrated examiner at six sites. Full-mouth plaque scores were recorded by assigning a binary score to each surface (1 for plaque present, 0 for absent) and by calculating the percentage of total tooth surfaces that revealed the presence of plaque detected by the use of tablet. Similarly, a full-mouth percentage bleeding score was calculated after assessing dichotomously the presence of bleeding on probing from the bottom of the pocket when probing with a manual probe with a force of 0.3n. Full-mouth PPD and recession of the gingival margin were recorded at the same time with measurements rounded to the nearest millimeter.

Non-surgical periodontal therapy Periodontal therapy was initiated within 1 month of the baseline screening examination. A standard cycle of periodontal therapy consisting of oral hygiene instructions, supra- and sub-gingival mechanical instrumentation of the root surface (scaling and root planning) was performed by two experienced therapists.

Local anesthesia was used as necessary. Patients relied on standard oral hygiene methods as instructed at the commencement of the study.

Post-treatment controls The objectives of the post-treatment appointments were to control and reinforce the oral hygiene habits of each subject, to monitor the early healing events and to report any adverse events or additional medications taken. In addition, the 1-week post-treatment visit served as a compliance control, as subjects were asked to return any medication not taken and/or the empty bottles. The number of pills not taken by the study subjects was documented.

Re-assessment examinations Reassessment visits occurred within a month and a half of the completion of the pharmacological treatment. During these appointments, the examiner recorded any changes in the medical history and repeated clinical periodontal parameters recorded at the basal visit.

Statistical analysis Age, FPG, HbA1C, tooth, and sounding depth were presented in means and standard deviation. The intra-group differences were calculated with Wilcoxon rank test. The inter-group differences were calculated with Mann-Whitney test. Sex, bacterial plaque, and bleed to the sounding were summarized using proportions and analyzed with the chi-square method. In all analyses, a P-value of <0.05 (two tailed) was considered statistically significant. All statistical analyses were conducted using SPSS software (IBM Corporation, Armonk, NY, USA) version 21.

Conditions

Periodontitis; Periodontal Pocket; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AMX-MET

AMX-MET Amoxicillin 500 mg + Metronidazole 250 mg. Capsules.

1 capsule tid during 7 days.

Group Type: ACTIVE_COMPARATOR

Amoxicillin 500 mg / Metronidazole 250 mg

Intervention Type: DRUG

Subjects were instructed to take a capsule three times a day for 7 days

Clindamycin

Clindamycin Clindamycin 300 mg + placebo. Capsules.

1 capsule tid during 7 days.

Group Type: EXPERIMENTAL

Clindamycin 300 mg

Intervention Type: DRUG

Subjects were instructed to take a capsule three times a day for 7 days

Interventions

Amoxicillin 500 mg / Metronidazole 250 mg

Subjects were instructed to take a capsule three times a day for 7 days

Intervention Type: DRUG

Clindamycin 300 mg

Subjects were instructed to take a capsule three times a day for 7 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients of both sexes
• Age >18 to 70 years
• Diagnosis of chronic periodontitis according to the 1999 International World Workshop for a Classification of Periodontal Diseases and Conditions
• History of type 2 diabetes
• HbA1C < 8 %
• Fasting plasma glucose (FPG) < 180 mg/dL.

Exclusion Criteria

• Aggressive periodontitis
• Pregnant or lactating females,
• Required antibiotic pre-medication for the performance of periodontal examination and treatment or received antibiotic treatment in the previous 3 months were excluded.
• A history of anti-inflammatory therapy within preceding six months
• Had received a course of periodontal treatment within the last 6 months,
• Allergies to penicillin, metronidazole or clindamycin,
• Not able to provide consent to participate in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro Universitario de Tonalá

OTHER

Sponsor Role: lead

Responsible Party

Arieh Roldán Mercado Sesma

Research professor associate B

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

CUT2017002

Identifier Type: -

Identifier Source: org_study_id