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Aim: In the present 6-month multicentre trial, the outcome of 2 different approaches to non-surgical treatment of chronic periodontitis, both involving the use of a locally delivered controlled-release doxycycline, was evaluated., Material and Methods: 105 adult patients with moderately advanced chronic periodontitis from 3 centres participated in the trial. Each patient had to present with at least 8 periodontal sites in 2 jaw quadrants with a probing pocket depth (PPD) of > or =5 mm and bleeding following pocket probing (BoP), out of which at least 2 sites had to be > or =7 mm and a further 2 sites > or =6 mm. Following a baseline examination, including assessments of plaque, PPD, clinical attachment level (CAL) and BoP, careful instruction in oral hygiene was given. The patients were then randomly assigned to one of two treatment groups: scaling/root planing (SRP) with local analgesia or debridement (supra- and subgingival ultrasonic instrumentation without analgesia). The "SRP" group received a single episode of full-mouth supra-/subgingival scaling and root planing under local analgesia. In addition, at a 3-month recall visit, a full-mouth supra-/subgingival debridement using ultrasonic instrumentation was provided. This was followed by subgingival application of an 8.5% w/w doxycycline polymer at sites with a remaining PPD of > or =5 mm. The patients of the "debridement" group were initially subjected to a 45-minute full-mouth debridement with the use of an ultrasonic instrument and without administration of local analgesia, and followed by application of doxycycline in sites with a PPD of > or =5 mm. At month 3, sites with a remaining PPD of > or =5 mm were subjected to scaling and root planing. Clinical re-examinations were performed at 3 and 6 months., Results: At 3 months, the proportion of sites showing PPD of < or =4 mm was significantly higher in the "debridement" group than in the "SRP" group (58% versus 50%; p<0.05). The CAL gain at 3 months amounted to 0.8 mm in the "debridement" group and 0.5 mm in the "SRP" group (p=0.064). The proportion of sites demonstrating a clinically significant CAL gain (> or =2 mm) was higher in the "debridement" group than in the "SRP" group (38% versus 30%; p<0.05). At the 6-month examination, no statistically significant differences in PPD or CAL were found between the two treatment groups. BoP was significantly lower for the "debridement" group than for the "SRP" group (p<0.001) both at 3- and 6 months. The mean total treatment time (baseline and 3-month) for the "SRP" patients was 3:11 h, compared to 2:00 h for the patients in the "debridement" group (p<0.001)., Conclusion: The results indicate that simplified subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be considered as a justified approach for non-surgical treatment of chronic periodontitis.