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Effect of Three Periodontal Therapies in Current Smokers and Non-Smokers

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ClinicalTrials.gov Identifier: NCT00066066
Recruitment Status : Completed
First Posted : August 5, 2003
Results First Posted : April 22, 2013
Last Update Posted : April 22, 2013
Sponsor:
Collaborator:
National Institute of Dental and Craniofacial Research (NIDCR)
Information provided by (Responsible Party):
The Forsyth Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Periodontitis
Periodontal Diseases
Interventions Procedure: Scaling and root planing
Drug: Metronidazole
Drug: Amoxicillin
Drug: Doxycycline
Enrollment 146

Recruitment Details Subjects with moderate to advanced chronic periodontitis were recruited to the clinical center at The Forsyth Institute. Subjects were recruited from the Boston area, subjects of any racial / ethnic group were accepted for study.
Pre-assignment Details Only 5 subjects dropped prior to randomization due to conflicts in scheduling or unable to adhere to the monitoring plan.
Arm/Group Title Scaling and Root Planing (SRP) Only NonSmokers SRP Only Smokers SRP and Metronidazole (MET) NonSmokers SRP and Metronidazole (MET) Smokers SRP and Amoxicillin, MET, Local Tetracycline NonSmokers SRP and Amoxicillin, MET, Local Tetracycline Smokers
Hide Arm/Group Description Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects. Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

Period Title: Overall Study
Started 27 22 30 20 27 20
Baseline 27 22 30 20 27 20
3 Month 21 17 23 16 22 15
6 Month 19 13 23 13 21 14
12 Month 18 11 21 11 19 9
Completed 21 [1] 18 [2] 23 [3] 16 [4] 24 [5] 15 [6]
Not Completed 6 4 7 4 3 5
Reason Not Completed
Lost to Follow-up             6             4             7             4             3             5
[1]
27 enrolled, 21 analyzed,18 subjects had complete data,3 subjects had data carried forward.
[2]
22 enrolled, 18 analyzed,11 subjects had complete data,7 subjects had data carried forward.
[3]
30 enrolled, 23 analyzed,21 subjects had complete data,2 subjects had data carried forward.
[4]
20 enrolled, 16 analyzed,11 subjects had complete data,5 subjects had data carried forward.
[5]
27 enrolled, 24 analyzed,19 subjects had complete data,5 subjects had data carried forward.
[6]
20 enrolled, 15 analyzed,9 subjects had complete data,6 subjects had data carried forward.
Arm/Group Title Scaling and Root Planing (SRP) Only SRP and Metronidazole (MET) SRP and Amoxicillin, MET and Locally Delivered Tetracycline Total
Hide Arm/Group Description Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

Total of all reporting groups
Overall Number of Baseline Participants 49 50 47 146
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 50 participants 47 participants 146 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
42
  85.7%
46
  92.0%
44
  93.6%
132
  90.4%
>=65 years
7
  14.3%
4
   8.0%
3
   6.4%
14
   9.6%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants 50 participants 47 participants 146 participants
50.3  (11.8) 50.3  (11.6) 48.0  (11.1) 49.5  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 50 participants 47 participants 146 participants
Female
21
  42.9%
23
  46.0%
20
  42.6%
64
  43.8%
Male
28
  57.1%
27
  54.0%
27
  57.4%
82
  56.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 49 participants 50 participants 47 participants 146 participants
49 50 47 146
1.Primary Outcome
Title Change in Mean Clinical Attachment Level.
Hide Description Periodontal diseases are clinically diagnosed by assessments of gingival inflammation and measurements of tissue destruction. The damage to the apparatus of support of the teeth is quantified using measurements of probing pocket depth (PD) and clinical attachment level (CAL). These measurements are obtained using a periodontal probe which is introduced into the gingival sulcus to determine the distance in millimeters from the gingival margin to the depth of the sulcus or pocket (PD). Since the gingival margin fluctuates in response to inflammation (hyperplasia) or might recede, a more accurate measure of loss of attachment is obtained using the CAL, which measures the distance from a “fixed” landmark on the tooth such as the cemento-enamel junction to the depth of the pocket. Changes in CAL from baseline were used to assess results obtained with the treatment of periodontal diseases.
Time Frame Baseline, 3, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 146 subjects, 117 were included in the analysis, who had 2 or fewer missing monitoring visits. 84 subjects had complete data, 23 subjects had one missing visit and 10 subjects had 2 missing visits. For the 33 subjects with missing visits, data were carried forward. 68 subjects were non smokers and 49 subjects were current smokers.
Arm/Group Title Scaling and Root Planing Only NonSmokers SRP Only Smokers SRP + Metronidazole NonSmokers SRP + Metronidazole Smokers SRP + MET + Amoxicillin + Doxycycline NonSmokers SRP + MET + Amoxicillin + Doxycycline Smokers
Hide Arm/Group Description:
Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects.
Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

Overall Number of Participants Analyzed 21 18 23 16 24 15
Mean (Standard Error)
Unit of Measure: mm
Changes in mean CAL from baseline to 3 months 0.11  (0.06) 0.10  (0.04) 0.21  (0.05) 0.08  (0.06) 0.29  (0.07) 0.28  (0.06)
Changes in mean CAL from baseline to 6 months 0.15  (0.06) 0.19  (0.05) 0.19  (0.07) 0.13  (0.07) 0.34  (0.07) 0.40  (0.08)
Changes in mean CAL from baseline to 12 months 0.11  (0.05) 0.24  (0.05) 0.26  (0.06) 0.17  (0.09) 0.41  (0.07) 0.39  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Scaling and Root Planing Only NonSmokers, SRP + Metronidazole NonSmokers, SRP + MET + Amoxicillin + Doxycycline NonSmokers
Comments The null hypothesis of no difference among treatment groups in non-smokers was tested by comparing change in mean CAL in individuals at 3 months post-therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments The p-value was not adjusted for multiple comparisons and the a priori threshold for significance was alpha = 0.05
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Scaling and Root Planing Only NonSmokers, SRP + Metronidazole NonSmokers, SRP + MET + Amoxicillin + Doxycycline NonSmokers
Comments The null hypothesis of no difference among treatment groups in non-smokers was tested by comparing change in mean CAL in individuals at 6 months post-therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments The p-value was not adjusted for multiple comparisons and the a priori threshold for significance was alpha = 0.05
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Scaling and Root Planing Only NonSmokers, SRP + Metronidazole NonSmokers, SRP + MET + Amoxicillin + Doxycycline NonSmokers
Comments The null hypothesis of no difference among treatment groups in non-smokers was tested by comparing change in mean CAL in individuals at 12 months post-therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments The p-value was not adjusted for multiple comparisons and the a priori threshold for significance was alpha = 0.05
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SRP Only Smokers, SRP + Metronidazole Smokers, SRP + MET + Amoxicillin + Doxycycline Smokers
Comments The null hypothesis of no difference among treatment groups in smokers was tested by comparing change in mean CAL in individuals at 3 months post-therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments The p-value was not adjusted for multiple comparisons and the a priori threshold for significance was alpha = 0.05
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection SRP Only Smokers, SRP + Metronidazole Smokers, SRP + MET + Amoxicillin + Doxycycline Smokers
Comments The null hypothesis of no difference among treatment groups in smokers was tested by comparing change in mean CAL in individuals at 6 months post-therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments The p-value was not adjusted for multiple comparisons and the a priori threshold for significance was alpha = 0.05
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection SRP Only Smokers, SRP + Metronidazole Smokers, SRP + MET + Amoxicillin + Doxycycline Smokers
Comments The null hypothesis of no difference among treatment groups in smokers was tested by comparing change in mean CAL in individuals at 12 months post-therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments The p-value was not adjusted for multiple comparisons and the a priori threshold for significance was alpha = 0.05
Method ANOVA
Comments [Not Specified]
Time Frame Adverse event data was collected over the entire course of the study for each enrolled subject.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Scaling and Root Planing (SRP) Only NonSmokers SRP Only Smokers SRP and Metronidazole (MET) NonSmokers SRP and Metronidazole (MET) Smokers SRP and Amoxicillin, MET, Local Tetracycline NonSmokers SRP and Amoxicillin, MET, Local Tetracycline Smokers
Hide Arm/Group Description Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects. Subjects received full mouth scaling and root planing (SRP) under local anesthesia.Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days). Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Metronidazole is an antibiotic that is particularly effective against Gram negative bacterial species.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

In addition to full mouth scaling and root planing under local anesthesia,subjects received systemically administered metronidazole (250 mg tid x 14 days) together with systemically administered amoxicillin (500 mg tid for 14 days) and local delivery of doxycycline (Atridox) at teeth with pockets > 4 mm. Maintenance SRP was performed every 3 months for the duration of the study in all subjects.

Tetracycline : Tetracycline is an antibiotic that has proved effective in killing bacteria in the periodontal pocket when applied locally.

All-Cause Mortality
Scaling and Root Planing (SRP) Only NonSmokers SRP Only Smokers SRP and Metronidazole (MET) NonSmokers SRP and Metronidazole (MET) Smokers SRP and Amoxicillin, MET, Local Tetracycline NonSmokers SRP and Amoxicillin, MET, Local Tetracycline Smokers
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Scaling and Root Planing (SRP) Only NonSmokers SRP Only Smokers SRP and Metronidazole (MET) NonSmokers SRP and Metronidazole (MET) Smokers SRP and Amoxicillin, MET, Local Tetracycline NonSmokers SRP and Amoxicillin, MET, Local Tetracycline Smokers
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/27 (3.70%)      0/22 (0.00%)      2/30 (6.67%)      2/20 (10.00%)      3/27 (11.11%)      1/20 (5.00%)    
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Death * [1]  0/27 (0.00%)  0 0/22 (0.00%)  0 1/30 (3.33%)  1 0/20 (0.00%)  0 1/27 (3.70%)  1 0/20 (0.00%)  0
Surgical and medical procedures             
hospitalizations   1/27 (3.70%)  1 0/22 (0.00%)  0 2/30 (6.67%)  2 2/20 (10.00%)  2 3/27 (11.11%)  3 1/20 (5.00%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
One death was due to cancer - SRP/MET/NonSmoker Group One death due to unknown causes
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Scaling and Root Planing (SRP) Only NonSmokers SRP Only Smokers SRP and Metronidazole (MET) NonSmokers SRP and Metronidazole (MET) Smokers SRP and Amoxicillin, MET, Local Tetracycline NonSmokers SRP and Amoxicillin, MET, Local Tetracycline Smokers
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/27 (29.63%)      4/22 (18.18%)      10/30 (33.33%)      3/20 (15.00%)      6/27 (22.22%)      5/20 (25.00%)    
Gastrointestinal disorders             
Gastrointestinal Upset   8/27 (29.63%)  8 4/22 (18.18%)  4 10/30 (33.33%)  10 3/20 (15.00%)  3 6/27 (22.22%)  6 5/20 (25.00%)  5
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Ricardo P Teles, DDS, DMSc
Organization: The Forsyth Institute
Phone: 617 892-8556
Responsible Party: The Forsyth Institute
ClinicalTrials.gov Identifier: NCT00066066     History of Changes
Other Study ID Numbers: NIDCR-14242
R01DE014242 ( U.S. NIH Grant/Contract )
First Submitted: August 1, 2003
First Posted: August 5, 2003
Results First Submitted: December 11, 2012
Results First Posted: April 22, 2013
Last Update Posted: April 22, 2013