Efficacy of Amoxicillin-metronidazole Compared to Clindamycin in Patients With Periodontitis and Diabetes
Primary Purpose
Periodontitis, Periodontal Pocket, Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Amoxicillin 500 mg / Metronidazole 250 mg
Clindamycin 300 mg
Sponsored by
About this trial
This is an interventional treatment trial for Periodontitis focused on measuring periodontitis, diabetes mellitus, systemic antimicrobials
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
AMX-MET
Clindamycin
Arm Description
AMX-MET Amoxicillin 500 mg + Metronidazole 250 mg. Capsules. 1 capsule tid during 7 days.
Clindamycin Clindamycin 300 mg + placebo. Capsules. 1 capsule tid during 7 days.
Outcomes
Primary Outcome Measures
Probing Depth
The size of the periodontal pocket
Secondary Outcome Measures
Sites With Plaques
0: no plaque
separate flecks of plaque at the cervical margin of the tooth
a thin continuous band of plaque (up to 1 mm) at the cervical margin of the tooth
a continuous band of plaque wider than 1 mm but covering less than one-third of the crown of the tooth
plaque covering at least one-third but less than two-thirds of the crown of the tooth
plaque covering two-thirds or more of the crown of the tooth. A higher scores mean a worse outcome
Sites With Bleeding on Probing
Refers to bleeding on probing 0: absence of inflammation
mild inflammation; a slight change in color, little change in the texture of any portion of but not the entire marginal or papillary gingival unit
mild inflammation; criteria as above but involving the entire marginal or papillary gingival unit
moderate inflammation; glazing, redness, edema, and/or hypertrophy of the marginal or papillary gingival unit 4; severe inflammation; marked redness, edema, and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration
Total Count of All Teeth Lost Across All Participants
The total count of all teeth lost in all participants.
Full Information
NCT ID
NCT03374176
First Posted
December 12, 2017
Last Updated
September 15, 2020
Sponsor
Centro Universitario de Tonalá
1. Study Identification
Unique Protocol Identification Number
NCT03374176
Brief Title
Efficacy of Amoxicillin-metronidazole Compared to Clindamycin in Patients With Periodontitis and Diabetes
Official Title
Efficacy of Amoxicillin-metronidazole Compared to Clindamycin in the Treatment of Periodontitis in Patients With Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
March 2014 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
September 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centro Universitario de Tonalá
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontitis, Periodontal Pocket, Diabetes Mellitus
Keywords
periodontitis, diabetes mellitus, systemic antimicrobials
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AMX-MET
Arm Type
Active Comparator
Arm Description
AMX-MET Amoxicillin 500 mg + Metronidazole 250 mg. Capsules.
1 capsule tid during 7 days.
Arm Title
Clindamycin
Arm Type
Experimental
Arm Description
Clindamycin Clindamycin 300 mg + placebo. Capsules.
1 capsule tid during 7 days.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin 500 mg / Metronidazole 250 mg
Intervention Description
Subjects were instructed to take a capsule three times a day for 7 days
Intervention Type
Drug
Intervention Name(s)
Clindamycin 300 mg
Intervention Description
Subjects were instructed to take a capsule three times a day for 7 days
Primary Outcome Measure Information:
Title
Probing Depth
Description
The size of the periodontal pocket
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Sites With Plaques
Description
0: no plaque
separate flecks of plaque at the cervical margin of the tooth
a thin continuous band of plaque (up to 1 mm) at the cervical margin of the tooth
a continuous band of plaque wider than 1 mm but covering less than one-third of the crown of the tooth
plaque covering at least one-third but less than two-thirds of the crown of the tooth
plaque covering two-thirds or more of the crown of the tooth. A higher scores mean a worse outcome
Time Frame
7 days
Title
Sites With Bleeding on Probing
Description
Refers to bleeding on probing 0: absence of inflammation
mild inflammation; a slight change in color, little change in the texture of any portion of but not the entire marginal or papillary gingival unit
mild inflammation; criteria as above but involving the entire marginal or papillary gingival unit
moderate inflammation; glazing, redness, edema, and/or hypertrophy of the marginal or papillary gingival unit 4; severe inflammation; marked redness, edema, and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration
Time Frame
7 days
Title
Total Count of All Teeth Lost Across All Participants
Description
The total count of all teeth lost in all participants.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy of Amoxicillin-metronidazole Compared to Clindamycin in Patients With Periodontitis and Diabetes
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