Multiple applications of flurbiprofen and chlorhexidine chips in patients with chronic periodontitis: a randomized, double blind, parallel, 2-arms clinical trial

Local delivery of antimicrobial agents as an adjunctive tool in the treatment of periodontal disease has been in use for over three decades now (Lindhe et al. 1979). An array of agents has been tested with varying degree of success. These are generally categorized into antibiotics, anti-bacterial agents and drugs modulating the inflammatory response. Several antibiotics have been tested: Goodson et al. (1979) have shown that tetracycline (Tc)-filled hollow fibres placed in gingival pockets had a beneficial effect on both periodontal pockets and sub-gingival bacterial flora. Tetracycline was also loaded onto polymer strips and showed superior results for pocket reduction and bleeding on probing (BOP) compared to scaling and root planing (SRP) alone (Friesen et al. 2002). Other biodegradable carriers containing Tc as the active ingredient were also shown to be useful in the treatment of chronic periodontitis (Schwach-Abdellaoui et al. 2001, Liu et al. 2004). Doxycycline (Doxy) gel (10–14%) has also been studied for local delivery in periodontal pockets and shown to have good sub-gingival anti-microbial properties (Kim et al. 2002). Garrett et al. (1999) in a multi-centre study reported that local application of Doxy hyclate alone was as effective in pocket reduction and attachment gain as SRP. Likewise, minocycline HCl, another member in the Tc group, has shown to improve both periodontal parameters and to reduce perio-pathogenic flora when applied locally (Jones et al. 1994, Yeom et al.1997, McColl et al. 2006, Goodson et al. 2007). Nakagawa et al. (1991) using 2% minocycline-HCl ointment combined with SRP in patients with recurrent periodontal pockets have shown after 3 months, greater pocket reduction and elimination of perio-pathogenic microflora in these sites compared with sites treated with SRP alone. Several other antibiotics including amoxicillin with clavulanic acid (Abu Fanas et al. 1991), metronidazole (Noyan et al. 1997), azythromycin (Pradeep et al. 2008) and niridazole (Barat et al. 2006) were tested for local delivery in periodontal pockets with varying degrees of success. Nonetheless, the use of low dose antibiotics in the periodontal pockets carries with it the risk of developing resistance, Kim et al. (2009) have concluded that local administration of Doxy can be identified in the systemic circulation at a level that has no antibiotic effect. Consequently, Larsen & Fiehn (1997) in an in vitro study and Rodrigues et al. (2004) in a human study, both reported the development of microbial resistance following the administration of metronidazole, minocycline and Tc. Antibiotic agents with anti-microbial properties have also been tested for local delivery in periodontal disease. Of these, chlorhexidine gluconate (CHX) has been most intensively studied and been used clinically for two decades now (Heasman et al. 2001, Azmak et al. 2002). Recently, Paolantonio et al. (2008) concluded a clinical and microbiological a randomized multi-centre study on the effect of CHX chips (PerioChip®) which is a cross-linked biodegradable matrix of hydrolysed gelatin containing chlorhexidine gluconate 2.5 mg, combined with SRP, to SRP alone. Pockets depth (PD) reduction and clinical attachment level (CAL) gain were significantly greater 6 months after treatment in the combined treatment group. These findings are in agreement with previous findings of yet another multi-centre study (Soskolne et al. 1997). Other agents with anti-microbial properties have shown to have some effect on periodontal disease when applied sub-gingivaly. These include sanguinarine (Polson et al. 1996), silver ions (Straub et al. 2001), hyalurinan (Johannsen et al. 2009), chitosan (Wang et al. 2009), superoxide (Petelin et al. 2000) and even herbal medication (Hirasawa et al. 2002, Sastravaha et al. 2003). Finally, drugs which modulate the host inflammatory response were also tested in both systemic and local application for the treatment of chronic periodontitis (Cetin et al. 2005). Tonetti & Chapple (2011) have recently concluded that non-steroidal anti-inflammatory drugs (NSAID) such as FBP may alter the course of periodontal disease in both animal model and human. Nonetheless, the use of these control release devises (CRD) had its limitations: Radvar et al. (1996) in a comparative study of three CRD-containing antibiotics reported that while pocket depth (PD) reduction was slightly greater in the SRP + CRD groups, CAL gain was not statistically significant compared to SRP alone. Pavia et al. (2004) in a meta-analysis of the effectiveness of SRP with CRD containing metronidazole compared to SRP alone showed significant but small (0.2 mm) greater CAL gain for the combined treatment. Thus, the purpose of the present randomized, double blind, parallel, 2-arm clinical study was to examine the safety and efficacy of frequent application of PerioChip® and Flurbiprofen Chip® (FBP group) in patients with chronic periodontitis.