Pharmacology: Clinical Studies:
In 2 double-blind, randomized, controlled clinical trials, 447 adult patients with periodontitis were entered, who had at least 4 pockets with probing depth of 5-8 mm that bled on probing. Patients studied were in good general health. Diabetics were excluded from the studies. PerioChip was not studied in acutely abscessed periodontal pockets. Patients were free of supragingival calculus prior to baseline. In these 2 studies, the effects of scaling and root planing (SRP) alone, and SRP followed by PerioChip treatment, were compared. All patients received full mouth SRP at baseline. If the pocket depth remained ≥5 mm at 3 and/or 6 months after initial treatment, another chip was placed into the pocket. Teeth treated with PerioChip were found to have significantly reduced probing pocket depth (PD) compared with those treated with SRP alone at 9 months after initial treatment, as shown in Table 1.
Click on icon to see table/diagram/image
PerioChip treatment resulted in a greater percentage of pockets and patients that showed an improvement in PD of ≥2 mm compared with SRP alone at 9 months, as shown in Table 2. The differences in improvement were statistically significant when analyzed on a per-patient-basis (p<0.005). PerioChip treatment maintained probing attachment level (PAL) compared with baseline or with SRP alone at 9 months. The effects of PerioChip on bleeding upon probing have not been established. In the 2 studies, there were no significant changes in plaque development or gingivitis. Smokers and non-smokers were enrolled in these studies; although non-smokers using PerioChip demonstrated significant improvement in PD, smokers demonstrated a trend towards improvement that did not reach statistical significance. This finding is consistent with the consensus that smoking is a risk factor in periodontal diseases. (See Table 2.)
Click on icon to see table/diagram/image
In the 2 clinical studies presented previously and an additional study (619 patients), the adverse effects of tooth staining or altered taste perception were not reported after the use of PerioChip.
PerioChip releases chlorhexidine in vitro
in a biphasic manner, initially releasing approximately 40% of the chlorhexidine within the first 24 hrs and then releasing the remaining chlorhexidine in an almost linear fashion for 7-10 days. This enzymatic release rate assay is an experimental collagenase assay that differs from the Regulatory Specification's Agar Release Rate Assay. This release profile may be explained as an initial burst effect, dependent on diffusion of chlorhexidine from the chip, followed by a further release of chlorhexidine as a result of enzymatic degradation.
In an in vivo
study of 18 evaluable adult patients, there were no detectable plasma or urine levels of chlorhexidine following the insertion of 4 PerioChips under clinical conditions. The concentration of chlorhexidine released from the PerioChip was determined in the gingival crevicular fluid (GCF) of these same subjects. In these subjects, a highly variable biphasic release profile for chlorhexidine was demonstrated, with GCF levels 4 hrs after chip insertion (mean: 1444±783 mcg/mL), followed by a 2nd peak at 72 hrs (mean: 1902±1073 mcg/mL ). In a 2nd study involving the insertion of 1 PerioChip under clinical conditions, the mean GCF level of chlorhexidine peaked at 1088±678 mcg/mL at 4 hrs. The mean GCF levels then declined in a highly erratic fashion to levels of 482±447 mcg/mL at 72 hrs without producing a true 2nd peak.
The results of these studies confirm a high degree of intersubject variability in chlorhexidine release from the PerioChip matrix in vivo
that was not seen in vitro
. Due to the nature and clinical use of the PerioChip dosage form, dose proportionality was not and would not be expected to be demonstrated between the 2 studies.
Chlorhexidine gluconate is active against a broad spectrum of microbes. The chlorhexidine molecule, due to its positive charge, reacts with the microbial cell surface, destroys the integrity of the cell membrane, penetrates into the cell, precipitates the cytoplasm, and the cell dies. Studies with PerioChip showed reductions in the numbers of the putative periodontopathic organisms Porphyromonas (Bacteroides) gingivalis
, Prevotella (Bacteroides) intermedia
, Bacteroides forsythus
and Campylobacter rectus (Wolinella recta)
after placement of the chip. No overgrowth of opportunistic organisms or other adverse changes in the oral microbial ecosystem were noted. The relationship of the microbial findings to clinical outcome has not been established.