The effect of locally delivered controlled-release doxycycline or scaling and root planing on periodontal maintenance patients over 9 months.

BACKGROUND: This research report evaluates clinical changes resulting from local delivery of doxycycline hyclate (DH) or traditional scaling and root planing (SRP) in a group of patients undergoing supportive periodontal therapy (SPT). METHODS: In all, 141 patients received either DH (67) or SRP (74) treatment in sites > or =5 mm on one-half of their dentition at baseline and month 4. RESULTS: Clinical results were determined at month 9. Baseline mean probing depth recordings were similar between the two groups (DH = 5.9 mm; SRP = 5.9 mm). Mean month 9 results showed similar clinical results for attachment level gain (DH 0.7 mm; SRP 0.8 mm) and probing depth reduction (DH 1.3 mm; SRP 1.1 mm). Percentage of sites showing > or =2 mm attachment level gain at month 9 was 24.7% in the DH group and 21.2% in the SRP group. Thirty-nine percent (39%) of DH sites and 38% of SRP sites showed > or =2 mm probing depth reduction. When treated sides of the dentition were compared to untreated sides, DH showed a difference in disease activity (> or =2 mm attachment loss) from 19.3% (untreated) to 7.2% (treated); and SRP from 14.3% (untreated) to 8.1% (treated). CONCLUSIONS: Results show that both DH without concomitant mechanical instrumentation and SRP were equally effective as SPT in this patient group over the 9-month study period.

Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis.

BACKGROUND: The clinical efficacy and safety of doxycycline hyclate (8.5% w/w) delivered subgingivally in a biodegradable polymer (DH) was compared to placebo control (VC), oral hygiene (OH), and scaling and root planing (SRP) in 2 multi-center studies. METHODS: Each study entered 411 patients who demonstrated moderate to severe periodontitis. Patients had 2 or more quadrants each with a minimum of 4 qualifying pockets > or =5 mm that bled on probing. At least 2 of the pockets were > or =7 mm. Treatment with DH, VC, OH, or SRP was provided at baseline and again at month 4. Clinical parameters were recorded monthly. RESULTS: DH and SRP resulted in nearly identical clinical changes over time in both studies. Mean 9 month clinical attachment level gain (ALG) was 0.8 mm for the DH group and 0.7 mm for the SRP group in Study 1, and 0.8 mm (DH) and 0.9 mm (SRP) in Study 2. Mean probing depth (PD) reduction was 1.1 mm for the DH group and 0.9 mm for the SRP group in Study 1 and 1.3 mm for both groups in Study 2. Frequency distributions showed an ALG > or =2 mm in 29% of DH sites versus 27% of SRP sites in Study 1 and 31% of DH sites versus 34% of SRP sites in Study 2. PD reductions > or =2 mm were seen in 32% of DH sites versus 31% of SRP sites in Study 1 and 41% of DH sites versus 43% of SRP sites in Study 2. Comparisons between DH, VC, and OH treatment groups showed DH treatment to be statistically superior to VC and OH. Safety data demonstrated a benign safety profile with use of the DH product. CONCLUSIONS: Results of this trial demonstrate that treatment of periodontitis with subgingivally delivered doxycycline in a biodegradable polymer is equally effective as scaling and root planing and superior in effect to placebo control and oral hygiene in reducing the clinical signs of adult periodontitis over a 9-month period. This represents positive changes resulting from the use of subgingivally applied doxycycline as scaling and root planing was not limited regarding time of the procedure or use of local anesthesia.

The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum.

The primary goal of this study was to characterize the release profile of doxycycline hyclate (8.5% w/w) from a biodegradable controlled-release delivery system (DH) placed in periodontal pockets. Pharmacokinetic data were obtained from gingival crevicular fluid (GCF), saliva, and serum of adult periodontitis patients. These results were compared to those obtained from individuals who received standard oral doses of doxycycline hyclate (200 mg on day 0, then 100 mg/day for 7 days). All participants presented with multiple pockets > or = 5 mm that bled upon probing. At the baseline visit patients receiving local drug delivery had all pockets > or = 5 mm that bled upon probing on one side of the mouth filled with DH. Drug retention was enhanced with 1 of 2 periodontal dressings (non-eugenol [NE] or 2-octyl cyanoacrylate [2-octyl]). Doxycycline concentrations were analyzed with the aid of reverse phase high performance liquid chromatography. GCF saliva, and serum samples were obtained just prior to drug delivery and then at hours 2, 4, 6, 8, 18, 24 and days 2, 3, 5, 7, and 8. GCF and saliva samples were also obtained at days 10, 14, 21, and 28. Thirty two subjects participated in the study; 13 in the NE group, 13 in the 2-octyl group, and 6 in the group taking oral doxycycline. The release of doxycycline in the GCF peaked at 2 hours (1473 microg/ml in the NE group, and 1986 microg/ml in the 2-octyl group). The mean concentration at day 7 was 309 microg/ml for the NE group and 148 microg/ml for the 2-octyl group. Minimal levels of drug were detected in the GCF of the oral doxycycline group with a peak concentration of 2.53 microg/ml at 12 hours. Salivary concentrations for both local delivery groups peaked at hour 2 (4.05 microg/ml for the NE group and 8.78 microg/ml for the 2-octyl group); by the end of day 1 levels were < or = 2 microg/ml. For subjects who took the oral doxycycline, salivary concentrations never exceeded 0.11 microg/ml. Serum concentrations of doxycycline for individuals receiving the local drug delivery never exceeded 0.1 microg/ml. For the oral doxycycline group serum concentrations ranged from 0.91 to 2.26 microg/ml over the 8 days data were collected. The high concentration of drug available at the treated sites coupled with the relatively low levels in the saliva and almost non-existent levels in the serum indicate that this biodegradable controlled-release delivery system displays an appropriate pharmacokinetic profile for the delivery of doxycycline into periodontal pockets.

Comparison of a bioabsorbable GTR barrier to a non-absorbable barrier in treating human class II furcation defects. A multi-center parallel design randomized single-blind trial.

This multi-center single-blind study compared clinical outcomes following guided tissue regeneration (GTR) treating human Class II furcation defects with a new polylactic-acid-based bioabsorbable barrier (test treatment) or a non-absorbable ePTFE barrier (control treatment). Clinical parameters evaluated were change in vertical attachment level (VAL), horizontal attachment level (HAL), probing depth (PD), and gingival margin location (REC). Surgical treatment resulted in clinically and statistically equivalent changes when comparisons were made between test and control treatments. VAL gain was 2.0 mm for test and 1.6 mm for control groups; HAL gain was 2.1 mm for both test and control groups. PD reduction was 2.3 mm for the test group and 2.1 mm for the control group. Test sites experienced an additional 0.3 mm of recession beyond baseline; control sites, 0.5 mm. Within-group comparisons showed that the amount of recession was not significantly different from baseline in the test group. Recession in the control group was significantly different from baseline. All other parameters in both the test and control groups were significantly different from baseline. Evaluation of safety data indicated no significant differences between test and control treatments, although there was a strong trend for the control group to have more postoperative abscess or suppuration than test sites (control = 11; test = 4; P = 0.06).

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. I. Study design, procedures, and management.

The design and conduct of a 9-month multi-center clinical trial to evaluate the safety and efficacy of subgingivally delivered 5% sanguinarium chloride (SC) and 10% doxycycline hyclate (DH) from a biodegradable drug delivery system in the treatment of adult periodontitis is described. The 3-group randomized study of 180 adults with moderate to severe periodontitis was a modified double-blind parallel design. One group received DH, one group received SC, and the other group received the vehicle control (VC). Patients selected had two quadrants with a minimum of four periodontal pockets > or = 5 mm in depth with two sites > or = 7 mm. All qualifying sites exhibited bleeding on gentle probing. Qualifying sites were treated at baseline and again at 4 months. Clinical response was assessed by measuring attachment level, probing depth, and bleeding on probing at monthly examinations at qualifying sites and the entire dentition. The plaque index was measured monthly to verify oral hygiene status. The parallel design afforded the opportunity to distinguish between treatment effectiveness of SC, DH, and VC independent of possible crossover effects. Also the effectiveness of oral hygiene in untreated sites of the mouth could be evaluated. Finally, treatment effects in moderate (5 to 6 mm) and deep (> or = 7 mm) pockets in both treated and untreated sites could be compared. The design was capable of simulating a periodontal practice maintenance program and assessing the response according to maintenance and treatment history. Study management procedures that emphasized center examiner and therapist training and adherence to protocol and procedures to reduce variability are described.

Guided tissue regeneration in human furcation defects after using a biodegradable barrier: a multi-center feasibility study.

This multi-center study evaluated guided tissue regeneration (GTR) in Class II furcation defects using a polylactic acid biodegradable barrier in 29 patients with mandibular and maxillary molar defects. Following an initial hygienic phase, surgical flaps were elevated, and the sites scaled and root planed. Furcation defect perimeter was measured and a customized barrier (thickness 600 to 750 mu) was applied to cover the defect. Barriers adhered directly to tooth and bone. At baseline, sites were measured for probing depth (PD) (6.0 +/- 0.2 [SE] mm), gingival margin location (GML) (-0.2 +/- 0.2 mm), and attachment level in both vertical (AL-V) (6.2 +/- 0.2 mm) and horizontal (AL-H) (5.4 +/- 0.2 mm) directions. After the surgical procedure, there was good compatibility between the gingival tissues and barrier material. Clinically, barriers fragmented and became displaced in 3 to 6 weeks. Substantial granulation tissue was sometimes present between barrier and root surfaces. Comprehensive periodontal examination parameters were measured 3, 4, 6, 9, and 12 months after baseline. A repeated measures ANOVA was used to evaluate changes from baseline. At 6 and 12 months postsurgery, GML was close to the presurgical level (-0.5 +/- 0.2 mm). There was clinically and statistically significant improvement in all other parameters: mean PD reduction (2.2 mm), AL-V gain (1.7 mm), and AL-H gain (2.5 mm). These results indicated favorable clinical regenerative outcomes after using this barrier material in Class II furcation defects in humans.