A Randomized, Double Blind - Wiley Online Library

Copy and paste this link to your website, so they can see this document directly without any plugins.


periodontal, Journal, with, Periodontology, local, reduction, study, delivery, were, Clinical, using, treatment, application, sites, these, reported, that, chronic, patients, gain, greater, periodontitis., effect, minocycline, have, chips, clinical, compared, shown, significant


Multiple applications of
flurbiprofen and chlorhexidine
chips in patients with chronic
periodontitis: a randomized,
double blind, parallel, 2-arms
clinical trial
Machtei EE, Hirsh I, Falah M, Shoshani E, Avramoff A, Penhasi A. Multiple
applications of flurbiprofen and chlorhexidine chips in patients with chronic
periodontitis: a randomized, double blind, parallel, 2-arms clinical trial. J Clin
Periodontol 2011; 38: 1037–1043. doi: 10.1111/j.1600-051X.2011.01779.x.
Aim: The aim of the present randomized, double blind, parallel, 2-arm clinical
study was to examine the safety and efficacy of frequent applications of
chlorhexidine chip (CHX) and flurbiprofen chip (FBP) in patients with chronic
Methods: Sixty patients were randomized into CHX and FBP groups. Following
OHI and scaling and root planing (SRP), baseline pocket depth (PD) measurements, gingival recession and bleeding on probing (BOP) were performed and
repeated at week 4 and 8. The assigned chip was placed at weeks 0, 1, 2, 3, 5, 7.
Results: Mean PD reduction in the CHX group was 2.08 mm (7.17 to 5.09,
p < 0.0001). Mean PD reduction in the FBP group was 2.27 mm (6.72 to 4.45,
p < 0.0001). Ninety-seven percentage and 95% of these sites exhibited PD
reduction  1 mm, while 38% and 34% of the sites exhibited PD  3 mm (FBP
and CHX, respectively). Clinical attachment level gain (1.66 and 1.95 mm,
respectively) was statistically significant (p < 0.0001). Baseline BOP dropped from
98% and 100% to 24% and 30% for the CHX and FBP groups, respectively
(p < 0.0001).
Conclusion: Frequent applications of CHX and FBP chips resulted in a significant improvement in the periodontal condition in these sites. Furthermore studies
will be required to compare this new treatment regimen to SRP or SRP with single chip application.
Eli E. Machtei1, Ilan Hirsh1,
Maher Falah1, Eyal Shoshani2,
Avi Avramoff2 and Adel Penhasi2
1Department of Periodontology, School of
Graduate Dentistry, Rambam Health Care
Campus and the Faculty of Medicine –
Technion (I.I.T.), Haifa, Israel; 2Dexcel
Pharma, Or Akiva, Israel
Key words: anti-infective therapy; chronic
periodontitis; controlled release device;
NSAID; PerioChip
Accepted for publication 17 July 2011
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 varyConflict of interest and source of funding statement
The study was a requested one and supported by a research grant from Dexcel®
Pharma Technologies, Israel. The following co-authors, Mr Eyal Shoshani, Dr Avi
Avramoff, and Dr Adel Penhasi, are employees of Dexcel Pharma the manufacturer
of PerioChip and FBP Chip.
© 2011 John Wiley & Sons A/S 1037
J Clin Periodontol 2011; 38: 1037–1043 doi: 10.1111/j.1600-051X.2011.01779.x
ing 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 subgingival 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 multicentre study on the effect of CHX
chips (PerioChip®) which is a crosslinked 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 antimicrobial 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 nonsteroidal 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 metaanalysis 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.
Material and methods
The study was initially approved by
the institutional review board of the
Rambam health care campus.
Patients seeking periodontal treatment at the RHCC School of Graduate Dentistry were screened for this
study [First patient enrolment-4th
August 2009; Last patient follow-up
(last visit)-8th June 2010]. To be
eligible for the study, the following
inclusion criteria were employed:
chronic periodontitis with at least
two teeth with periodontal pockets of
5–9 mm in depth (potential target
teeth); demonstrating BOP in at least
one site; radiographic evidence of
alveolar bone loss. Patients were
excluded for the following reasons: (i)
tooth-related pathology that might
be associated with the periodontal
pocket; (ii) presence of three or more
adjacent periodontal pockets on the
same potential target tooth; (iii) systemic antibiotic therapy or use of
NSAIDs prior to study entry (6 and
2 weeks, respectively) and throughout the study duration; (iv) usage of
medication known to potentially
result in gingival overgrowth; (v) type
I diabetes or non-stable type II; (vi)
known allergies to CHX or NSAID.
Eligible patients received a
detailed explanation on the nature of
the study and the alternatives, after
which they signed an informed
consent form. Next, full-mouth SRP
was performed together with oral
hygiene instructions. One to two
weeks later, baseline measurements
were obtained and the patients were
randomized using predetermined
computer-generated randomization
scheme to receive either the PerioChip® (CHX group) or the FBP group.
Randomized allocation sequence was
done by using pre-determined computer-generated randomization scheme
(SAS® version 9.2) to receive balanced
© 2011 John Wiley & Sons A/S
1038 Machtei et al.
random allocation of patients into the
two study treatment. Only eligible
patients at baseline visit were assigned
with a sequenced randomization number. Each randomization number was
randomly assigned to one of the two
treatments FBP chip or CHX chip.
The identity of the two treatments was
kept blinded from the investigator
and from the patient (double blind
randomized trial design). In addition,
one set of envelopes was provided to
the investigator containing individual
randomization codes; in event of an
emergency, an unblinding breaking
procedure was implemented. The
randomized allocation sequence was
generated by a statistician. The investigator was responsible for the
patients’ enrolment. The patients
were assigned randomly to one of the
two blinde study treatments by the
Chips were inserted sub-gingivally
as per the manufacturer’s instruction
for use. At weeks 1, 2, 3, 5 and 7 the
same type of chip was re-inserted (in
sites were insertion was met by resistance, PD was performed and if
<5 mm, the chip was not inserted).
Clinical measurements, which
included PD, gingival recession (R)
and BOP, were performed (using
UNC probe; Hu-friedy, Chicago, IL,
USA) at screening 0, 4 and 8 weeks
(flow chart, Fig. 1). Clinical attachment level was calculated as the sum
of PD and R. PD reduction,
0–8 weeks was defined as the primary outcome variable, while CAL
gain and changes in per cent sites
with BOP 0–8 weeks were set as
secondary outcome variables.
Patients were instructed to report
of any adverse event (AE); furthermore, at each visit they were actively
approached to inquire of any AE
that they might have experienced.
A total of 60 patients were
recruited into the study, 30 in each
group. Sample size was determined
using a power calculation analysis to
detect significant changes in PD
(baseline to 8 weeks), for each treatment modality. Of these, 28 were
female patients and 32 male patients
with slightly greater female: male
ratio in the CHX group (68%)
compared to 38% in the FBP group
(p = 0.02, Fisher’s exact test). One
patient (CHX group) withdrew
(attended only the baseline visit);
consequently, 59 patients, 30 FBP
and 29 CHX completed the study
and are reported in the present article. Less than 10% of these patients
were smokers: three in the FBP and
two in the CHX group.
Statistical methodology
For each chosen pocket in a patient,
we measured repeatedly at three main
time points: 0, 4 and 8 weeks, three
main parameters, PPD, CAL, and
BOP. PPD and CAL are continuous
parameters assumed to be approximately normally distributed, and
BOP is a binary parameter. The
parameters (PPD, CAL and BOP)
measured for a specific pocket and a
specific time point were modelled by
a generalized model (Nelder & Wedderburn 1972) with repeated covariate structure for specific patients
(each correlated patient structure
includes two different pockets with at
least three time points).
To model the covariance structure in a patient the Generalized
Estimating Equations (GEE) method
proposed by Liang & Zeger (1986)
was used.
For normal distributed variables
(PPD, CAL) an identity link was
used, for binary parameters (BOP,
change of at least 1 mm, etc.) a logit
link was used.
We used age and gender as confounding variables. Visit, preparation and the interaction between
visit and preparation are the explanatory variables.
The subject was the randomization
number, and was used for the repeated
structure in the GEE equations.
Specific contrasts for the visit
preparation were used to compute
elected differences with 95% confidence intervals needed for our analysis. All treatment comparisons were
two-sided at the 0.05 level of significance. The primary time-point for all
analyses was 8 weeks.
Study visits
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 8 Visit 9
Week –1
Week 0
Week 1 Week 2 Week 3 Week 4 Week5 Week 7 Week 8
Eligibility X X
Pocket (site)
Supra-gingival scaling X
Oral hygiene
Randomization X
Chip placement X X X X X X
Adverse events
Fig. 1. Study timeline.
© 2011 John Wiley & Sons A/S
Multiple application of CHX & FBP chips in periodontitis 1039
Similar models were built for categorized variables such as success to
achieve 1 or 2 mm reduction in PD.
Mean baseline PD was 7.17 ±
0.14 mm and 6.72 ± 0.13 mm for the
CHX and FBP groups, respectively,
which were very similar to the screening measurements for both groups
(7.29 and 6.78 mm, respectively).
Mean PD reduction (Fig. 2), from
baseline to week 8 for CHX group
was 2.08 ± 0.13 mm (7.17 to 5.09)
which was statistically significant
(p < 0.0001; GEE model). Mean PD
reduction from baseline to week 8
visit for the FBP group was
2.27 ± 0.15 mm (6.72 to 4.45) which
was also statistically different
(p < 0.0001; GEE model). PD reduction 0–8 weeks was not different
between groups (2.08 ± 0.13 mm for
the CHX group and 2.2 ± 0.15 mm
for the FBP groups; p > 0.05). When
the extent of PD reduction was
dichotomized, almost all these sites
(95% and 97% for the CHX and
FBP groups, respectively) had at
least 1 mm reduction between baseline and 8 weeks (Table 1). More
important, almost three quarters of
these sites (72% and 73% for the
CHX and FBP groups, respectively)
had at least 2 mm reduction in PD
and just over one-third of all these
sites (34% and 38% for the CHX
and FBP groups, respectively) had
3 mm or more pocket reduction in
these sites. Small proportions of
these pockets (7–17%) had a
startling 4 mm. PD reduction during
this period.
Likewise, mean CAL reduction
(Fig. 3) from baseline to week 8 for
CHX group was 1.66 mm (8.33 to
6.67) which was statistically significant (p < 0.0001; GEE model).
Mean CAL reduction from baseline
to week 8 for FBP group was
1.95 mm (7.68 to 5.73) which was
statistically significant (p < 0.0001;
GEE model). Again, the differences
between the groups were not statistically significant (p > 0.05).
Bleeding on probing was present,
at baseline in all but few of these
sites (100% and 98% for the CHX
and FBP groups, respectively). These
proportions dropped significantly at
4 weeks (48% and 45%) and further
at week 8 (24% and 30%). Again,
these proportions were not statistically different between the two
groups in any of these time points
(Fig. 4). The difference between
treatments was not significant
(p = 0.42, Fisher’s Exact test).
On visit 7, 10 sites in the CHX
group and 14 sites in the FBP group
had PD <5 mm which precluded the
placement of the chip. Likewise, on
the final visit 14 and 19 sites, respectively, had shallow pockets.
Data were further sorted to
compare treatment response between
single versus multi-rooted teeth
(Table 2). PD reduction in the singlerooted teeth (1.82 and 2.73 mm for
the CHX and FBP groups, respectively) was not significantly different
(GEE) compared to multi-rooted
teeth (2.15 and 2.16 mm for the CHX
and FBF groups, respectively). Likewise, CAL gain and BOP reduction
between baseline and 8 weeks were
Related AEs were minimal in
both groups. These included mild
gingival pain (2 FBP, 1 CHX),
dentinal pain (1 FBP, 3 CHX), headache (0 FBP, 1 CHX) and gingivitis
(0 FBP, 1 CHX). None of the
patients in either group had experienced any severe adverse reaction to
these chips.
PD reduction (mm ± SE)
Screening Baseline Week 4 Week 8
m m CHX
Fig. 2. Primary endpoint – PD reduction.
8.45 8.33
Screening Baseline Week 4 Week 8
m m ±
Fig. 3. CAL reduction – baseline to 8 weeks.
Table 1. Pocket depth reduction (dicatomized 1-4)
At least 1 mm reduction At least 2 mm reduction At least 3 mm reduction At least 4 mm reduction
BL-Wk.4 BL-Wk.8 BL-Wk.4 BL-Wk.8 BL-Wk.4 BL-Wk.8 BL-Wk.4 BL-Wk.8h
FBP 83% (50/60) 97% (58/60) 30% (18/60) 73% (44/60) 8% (5/60) 38% (23/60) 0% (0/60) 17% (10/60)
CHX 81% (47/58) 95% (55/58) 28% (16/58) 72% (42/58) 2% (1/58) 34% (20/58) 0% (0/60) 7% (4/58)
© 2011 John Wiley & Sons A/S
1040 Machtei et al.
Frequent application of CHX and
FBP chips together with single session of SRP at baseline resulted in a
mean PD reduction of more than
2 mm within 8 weeks in patients
with chronic periodontitis.
Likewise, van Steenberghe et al.
(1999) in a 1-year study of repeated
minocycline application reported
mean PD reduction of 1.9 mm in
sites with initial PD >5 mm. Slightly
smaller PD reduction (1.7 mm) was
reported by Riep et al. (1999) using
repeated metronidazole application
in maintenance patients.
Mean CAL gain in the present
study was 1.66–1.95 mm. These
results exceed those of Friesen et al.
(2002) study which reported mean
CAL gain of 0.18 mm after 3 months
when using repeated local application
of Tc containing strips; while in other
studies where repeated local delivery
system (LDS) was used, CAL gains
after 3 months were 1.1 mm using
minocycline (van Steenberghe et al.
1999) and 1.31 mm using metronidazole (Riep et al. 1999). The greater
CAL gain in the present study might
be associated with the greater intensity of the application of the chips;
this in turn results in higher local
concentration of the drug that might
be responsible for the greater effect.
Bogren et al. (2008) using Doxy gel
have shown that repeated annual
application did not result any beneficial effect (neither clinically nor
microbiologically) in maintenance
patients with PD  5 mm.
Repeated LDS of antimicrobial
agents is not necessarily limited to
non-surgical therapy. Yoshinari et al.
(2001) examined the effect of repeated
minocycline application on the success of guided tissue regeneration
using expanded polytetrafluoroethylene (ePTFE( membranes and
reported significantly greater CAL
gain (3.0 mm) compared to ePTFE
alone (2.0 mm) in 1–3 wall intra-bony
defects. Likewise, our group (Machtei
et al. 2003) in a similar previous study
of GTR in mandibular class II defects
in smokers, reported greater CAL
gain and bone regeneration in
patients who had repeated metronidazole application as part of an aggressive anti-infective regiment.
Practically all sites had at least
1 mm. PD reduction at the end of the
study, while 75% had  2 mm. PD
reduction and over 1/3 of the sites
exhibited PD reduction  3 mm.
Thus, a great number of these sites
initially targeted for surgical periodontal therapy, had improved to the
extent that no further active therapy
was needed. van Steenberghe et al.
(1999) using similar protocol with minocycline reported  2 mm PD
reduction in approximately 50% of
the sites that were initially  5 mm.
The magnitude of improvement
in PD and CAL in the present study
(1.66–2.27 mm) was by far greater
than what was reported in most
studies for single application of
LDS. However, the lack of SRP only
control in the present study precludes any attempt to estimate the
proportion of the adjunctive effect of
the two chips. Single application of
CHX chips (Heasman et al. 2001)
resulted in mean PD of 0.55–
0.78 mm after 3 and 6 months. To
the contrary, Eickholz et al. (2002)
reported greater PD reduction
(3.1 mm) and similar CAL gain
using SRP + single DOXY gel application, is 110 single rooted teeth.
Pavia et al. (2003) in a meta-analysis
of the efficacy of Tc (Tc fibres; Doxy
and minocycline gel) in chronic periodontitis patients reported mean
additional PD reduction and CAL
gain of 0.6–0.8 mm and 0.33–
0.74 mm for SRP + local Tc over
SRP only.
Approximately 25% of these sites
still had BOP at 8 weeks compared
to 98–100% at baseline. This marked
reduction in the proportions of sites
that bled on probing represents significant reduction in inflammation
and possibly bacterial load in these
sites. Bogren et al. (2008) reported
37% of the sites to still exhibit BOP
3 months after SRP + LDS with
Doxy; however, at baseline only
51% of these sites had BOP, thus
the overall reduction in this study
was merely 27% compared to 75%
in our study. Likewise, McColl et al.
(2006) in a 12 months randomized
control study using 2% minocycline
gel reported the drop in BOP to
range between 0% and 50.5%.
Goodson et al. (2007) have shown
that LDS of antimicrobial drugs had
a significant effect in reducing the
red-complex bacteria in the periodontal pocket. The larger reduction
in BOP observed in the present
study is likely due to the anti-infective effect that the frequent application of these chips had on the
microbial flora (CHX) and inflammatory response (FBP).
The CHX chips resulted in similar and even greater response comTable 2. Changes in PD: multi-rooted versus single-rooted teeth
Tooth type Tooth type
Multi-root Single-root Other Multi-root Single-root Other
Baseline/Screening 0.09 0 0 0.15 0.18 0.5
Week 4/Baseline 1.16 1.55 1 1.15 1.09 0.83
Week 8/Baseline 2.16 2.73 2.2 2.15 1.82 2.17
98% 100% 100% 98%
48% 45%
o f b s it es b le ed in g Screening Baseline Week 4 Week 8
Fig. 4. Changes in bleeding on probing.
© 2011 John Wiley & Sons A/S
Multiple application of CHX & FBP chips in periodontitis 1041
pared to the FBP chips. This is the
first study ever to compare these two
agents which have such a different
mode of action. Few studies are
available where LDS containing
NSAIDs were tested for the treatment of periodontal disease. Williams et al. (1988) using FBP gel
that was applied daily into the gingival margins of beagle dogs, reported
less bone loss and tooth loss compared to untreated animals. Li et al.
(1996) using daily application of
ketoprofen gel in rhesus monkeys
reported alveolar bone gain compared to placebo control which
exhibited net bone loss in an experimental periodontitis and spontaneous periodontitis model. This
beneficial effect of the FBP reported
in the present study was similar to
that found for the CHX chips. Thus,
further studies on drugs with local
anti-inflammatory effect are warranted. These findings of a sizeable
improvement, in both the CHX chip
(with its anti-bacterial properties)
and the FBP chips (with its antiinflammatory properties), would
tend to suggest that if both chips are
used consecutively or simultaneously,
it might result in even greater
improvement in clinical parameters
compared to when each of them is
used individually; however, this
hypothesis will need furthermore
research to be substantiated.
In conclusion the frequent use of
CHX or FBP chips in conjunction
with single SRP visit, resulted in
marked improvement in the periodontal condition in patients with
chronic periodontitis. To further
assess if this new mode of application is superior to single application
or SRP only treatment, furthermore
studies with such controls will be
The authors thank Ms Liron Eliezer
for the coordination of this study.
Abu Fanas, S. H., Drucker, D. B. & Hull, P. S.
(1991) Evaluation of acrylic strips containing
amoxycillin with clavulanic acid for local drug
delivery. Journal of Dentistry 19, 92–96.
Azmak, N., Atilla, G., Luoto, H. & Sorsa, T.
(2002) The effect of subgingival controlledrelease delivery of chlorhexidine chip on clinical
parameters and matrix metalloproteinase-8
levels in gingival crevicular fluid. Journal of
Periodontology 73, 608–615.
Barat, R., Srinatha, A., Pandit, J. K., Ridhurkar,
D., Balasubramaniam, J., Mittal, N. & Mishra,
D. N. (2006) Niridazole biodegradable inserts
for local long-term treatment of periodontitis:
possible new life for an orphan drug. Drug
Delivery 13, 365–373.
Bogren, A., Teles, R. P., Torresya, p. G., Haffajee, A. D., Socransky, S. S. & Wennström,
J. L. (2008) Locally delivered doxycycline during supportive periodontal therapy: a 3-year
study. Journal of Periodontology 79, 827–835.
Cetin, E. O., Buduneli, N., Atlihan, E. & Kirilmaz, L. (2005) In vitro studies of a degradable
device for controlled-release of meloxicam.
Journal of Clinical Periodontology 32, 773–
Eickholz, P., Kim, T. S., Bürklin, T., Schacher, B.,
Renggli, H. H., Schaecken, M. T., Holle, R.,
Kübler, A. & Ratka-Krüger, P. (2002) Nonsurgical periodontal therapy with adjunctive
topical doxycycline: a double-blind randomized
controlled multicenter study. Journal of Clinical
Periodontology 29, 108–117.
Friesen, L. R., Williams, K. B., Krause, L. S. &
Killoy, W. J. (2002) Controlled local delivery
of tetracycline with polymer strips in the
treatment of periodontitis. Journal of
Periodontology 73, 9–13.
Garrett, S., Johnson, L., Drisko, C. H., Adams,
D. F., Bandt, C., Beiswanger, B., Bogle, G.,
Donly, K., Hallmon, W. W., Hancock, E. B.,
Hanes, P., Hawley, C. E., Kiger, R., Killoy,
W., Mellonig, J. T., Polson, A., Raab, F. J.,
Ryder, M., Stoller, N. H., Wang, H. L.,
Wolinsky, L. E., Evans, G. H., Harrold, C. Q.,
Arnold, R. L., Nasi, H. F., Newell, D. H.,
MacNeil, R. L., MacNeill, S., Spolsky, V. W.,
Duke, S. P., Polson, A. & Southard, G. L.
(1999) Two multi-center studies evaluating
locally delivered doxycycline hyclate, placebo
control, oral hygiene, and scaling and root
planing in the treatment of periodontitis. Journal of Periodontology 70, 490–503.
Goodson, J. M., Gunsolley, J. C., Grossi, S. G.,
Bland, P. S., Otomo-Corgel, J., Doherty, F. &
Comiskey, J. (2007) Minocycline HCl
microspheres reduce red-complex bacteria in
periodontal disease therapy. Journal of
Periodontology 78, 1568–1579.
Goodson, J. M., Haffajee, A. & Socransky, S. S.
(1979) Periodontal therapy by local delivery of
tetracycline. Journal of Clinical Periodontology
6, 83–92.
Heasman, P. A., Heasman, L., Stacey, F. & McCracken, G. I. (2001) Local delivery of chlorhexidine gluconate (PerioChip) in periodontal
maintenance patients. Journal of Clinical Periodontology 28, 90–95.
Hirasawa, M., Takada, K., Makimura, M. &
Otake, S. (2002) Improvement of periodontal
status by green tea catechin using a local
delivery system: a clinical pilot study. Journal
of Periodontal Research 37, 433–438.
Johannsen, A., Tellefsen, M., Wikesjö, U. M. E.
& Johannsen, G. (2009) Local delivery of hyaluronan as an adjunct to scaling and root
planing in the treatment of chronic periodontitis. Journal of Periodontology 80, 1493–1497.
Jones, A. A., Kornman, K. S., Newbold, D. A. &
Manwell, M. A. (1994) Clinical and microbiological effects of controlled-release locally
delivered minocycline in periodontitis. Journal
of Periodontology 65, 1058–1066.
Kim, T. S., Bürklin, T., Schacher, B., Ratka-Krüger, P., Schaecken, M. T., Renggli, H. H., Fiehn, W. & Eickholz, P. (2002) Pharmacokinetic
profile of a locally administered doxycycline gel
in crevicular fluid, blood, and saliva. Journal of
Periodontology 73, 1285–1291.
Kim, T. S., Lee, S. H., Eickholz, P., Zimmer, H.
& Kim, C. K. (2009) Systemic detection of
doxycycline after local administration. Acta
Odontologica Scandinavia 10, 1–8.
Larsen, T. & Fiehn, N. E. (1997) Development of
resistance to metronidazole and minocycline in
vitro. Journal of Clinical Periodontology 24,
Li, K. L., Vogel, R., Jeffcoat, M. K., Alfano, M.
C., Smith, M. A., Collins, J. G. & Offenbacher,
S. (1996) The effect of ketoprofen creams on
periodontal disease in rhesus monkeys. Journal
of Periodontal Research 31, 525–532.
Liang, K. Y. & Zeger, S. L. (1986) Longitudinal
data analysis using generalized linear models.
Biometrika 73, 3–22.
Lindhe, J., Heijl, L., Goodson, J. M. & Socransky,
S. S. (1979) Local tetracycline delivery using hollow fiber devices in periodontal therapy. Journal
of Clinical Periodontology 6, 141–149.
Liu, D. Z., Chen, W. P., Lee, C. P., Wu, S. L.,
Wang, Y. C. & Chung, T. W. (2004) Effects of
alginate coated on PLGA microspheres for
delivery tetracycline hydrochloride to periodontal pockets. Journal of Microencapsulation 21,
Machtei, E. E., Oettinger-Barak, O. & Peled, M.
(2003) Guided tissue regeneration in smokers:
effect of aggressive anti-infective therapy in
Class II furcation defects. Journal of Periodontology 74, 579–584.
McColl, E., Patel, K., Dahlen, G., Tonetti, M.,
Graziani, F., Suvan, J. & Laurell, L. (2006)
Supportive periodontal therapy using mechanical instrumentation or 2% minocycline gel: a
12 month randomized, controlled, single
masked pilot study. Journal of Clinical
Periodontology 33, 141–150.
Nakagawa, T., Yamada, S., Oosuka, Y., Saito, A.,
Hosaka, Y., Ishikawa, T. & Okuda, K. (1991)
Clinical and microbiological study of local
minocycline delivery (Periocline) following
scaling and root planing in recurrent periodontal pockets. Bulletin Tokyo Dental College 32,
Nelder, J. A. & Wedderburn, R. W. M. (1972)
Generalized linear models. Journal of the Royal
Statistical Society (Series A) 135, 370–384.
Noyan, U., Yilmaz, S., Kuru, B., Kadir, T., Acar,
O. & Büget, E. (1997) A clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients.
Journal of Clinical Periodontology 24, 158–165.
Paolantonio, M., D’Angelo, M., Grassi, R. F.,
Perinetti, G., Piccolomini, R., Pizzo, G., Annunziata, M., D’Archivio, D., D’Ercole, S.,
Nardi, G. & Guida, L. (2008) Clinical and
microbiologic effects of subgingival controlledrelease delivery of chlorhexidine chip in the
treatment of periodontitis: a multicenter study.
Journal of Periodontology 79, 271–282.
Pavia, M., Nobile, C. G. & Angelillo, I. F. (2003)
Meta-analysis of local tetracycline in treating
chronic periodontitis. Journal of Periodontology
74, 916–932.
Pavia, M., Nobile, C. G., Bianco, A. & Angelillo,
I. F. (2004) Meta-analysis of local metronidazole in the treatment of chronic periodontitis.
Journal of Periodontology 75, 830–838.
Petelin, M., Pavlica, Z., Ivanusa, T., Sentjurc, M.
& Skaleric, U. (2000) Local delivery of
liposome-encapsulated superoxide dismutase
and catalase suppress periodontal inflammation
© 2011 John Wiley & Sons A/S
1042 Machtei et al.
in beagles. Journal of Clinical Periodontology
27, 918–925.
Polson, A. M., Stoller, N. H., Hanes, P. J.,
Bandt, C. L., Garrett, S. & Southard, G. L.
(1996) 2 multi-center trials assessing the clinical
efficacy of 5% sanguinarine in a biodegradable
drug delivery system. Journal of Clinical
Periodontology 2, 782–788.
Pradeep, A. R., Sagar, S. V. & Daisy, H. (2008)
Clinical and microbiologic effects of subgingivally delivered 0.5% azithromycin in the treatment of chronic periodontitis. Journal of
Periodontology 79, 2125–2135.
Radvar, M., Pourtaghi, N. & Kinane, D. F.
(1996) Comparison of 3 periodontal local antibiotic therapies in persistent periodontal pockets. Journal of Periodontology 67, 860–865.
Riep, B., Purucker, P. & Bernimoulin, J. P. (1999)
Repeated local metronidazole-therapy as
adjunct to scaling and root planing in maintenance patients. Journal of Clinical Periodontology 26, 710–715.
Rodrigues, R. M., Gonçalves, C., Souto, R.,
Feres-Filho, E. J., Uzeda, M. & Colombo,
A. P. (2004) Antibiotic resistance profile of the
subgingival microbiota following systemic or
local tetracycline therapy. Journal of Clinical
Periodontology 31, 420–427.
Sastravaha, G., Yotnuengnit, P., Booncong, P. &
Sangtherapitikul, P. (2003) Adjunctive periodontal treatment with Centella asiatica and
Punica granatum extracts. A preliminary study.
Journal of the International Academy of
Periodontology 5, 106–115.
Schwach-Abdellaoui, K., Monti, A., Barr, J.,
Heller, J. & Gurny, R. (2001) Optimization of
a novel bioerodible device based on autocatalyzed poly(ortho esters) for controlled
delivery of tetracycline to periodontal pocket.
Biomaterials 22, 1659–1666.
Soskolne, W. A., Heasman, P. A., Stabholz, A.,
Smart, G. J., Palmer, M., Flashner, M. & Newman, H. N. (1997) Sustained local delivery of
chlorhexidine in the treatment of periodontitis:
a multi-center study. Journal of Periodontology
68, 32–38.
van Steenberghe, D., Rosling, B., Söder, P. O.,
Landry, R. G., van der Velden, U., Timmerman, M. F., McCarthy, E. F., Vandenhoven,
G., Wouters, C., Wilson, M., Matthews, J. &
Newman, H. N. (1999) A 15-month evaluation
of the effects of repeated subgingival minocycline in chronic adult periodontitis. Journal of
Periodontology 70, 657–667.
Straub, A. M., Suvan, J., Lang, N. P., Mombelli,
A., Braman, V., Massaro, J., Friden, P. & Tonetti, M. S. (2001) Phase 1 evaluation of a local
delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability. Journal of Periodontal Research 36,
Tonetti, M. S. & Chapple, I. L. (2011) Biological
approaches to the development of novel periodontal therapies – consensus of the Seventh
European Workshop on Periodontology. Journal of Clinical Periodontology 38(Suppl. 11),
Wang, L. C., Wu, H., Chen, X. G., De Li, L., Ji,
Q. X., Liu, C. S., Yule, J., Ran, C. & Zha,
Q. S. (2009) Biological evaluation of a novel
chitosan-PVA-based local delivery system for
treatment of periodontitis. Journal of Biomedical Material Research 91, 1065–1076.
Williams, R. C., Jeffcoat, M. K., Howell, T. H.,
Reddy, M. S., Johnson, H. G., Hall, C. M. &
Goldhaber, P. (1988) Topical flurbiprofen
treatment of periodontitis in beagles. Journal of
Periodontal Research 23, 166–169.
Yeom, H. R., Park, Y. J., Lee, S. J., Rhyu, I. C.,
Chung, C. P. & Nisengard, R. J. (1997) Clinical and microbiological effects of minocyclineloaded microcapsules in adult periodontitis.
Journal of Periodontology 68, 1102–1109.
Yoshinari, N., Tohya, T., Kawase, H., Matsuoka,
M., Nakane, M., Kawachi, M., Mitani, A.,
Koide, M., Inagaki, K., Fukuda, M. & Noguchi, T. (2001) Effect of repeated local minocycline administration on periodontal healing
following guided tissue regeneration. Journal of
Periodontology 72, 284–295.
Eli E. Machtei
Department of Periodontology
School of Graduate Dentistry
Rambam HCC, PO Box 9602
Haifa 31096, Israel
E-mail: machtei@rambam.health.gov.il
Clinical Relevance
Scientific rationale for the study:
The use of LDS has shown some
benefit in pocket reduction and
resolution of inflammation. However, the extent of this improvement has been limited. CHX and
to a lesser extent NSAID have
shown beneficial effect in modulating periodontal inflammation
when applied into the periodontal pocket. The aim of the present study was to explore the
efficacy and safety of a new drug
(FBP chip) and well-known LDS
medication (CHX Chip) using
a new, intensive placement protocol.
Principal findings: Mean PD
reduction (2.08–2.27 mm), CAL
gain (1.66–1.95 mm) and drop in
BOP (68–76%) in the two groups
was greater than previously
reported with LDS using standard
single application.
Practical implications: This new
regimen for LDS application
might replace the current single
application mode to gain better
improvement in periodontal
parameters in patients with
chronic periodontitis.
© 2011 John Wiley & Sons A/S
Multiple application of CHX & FBP chips in periodontitis 1043

PDF Document reader online

This website is focused on providing document in readable format, online without need to install any type of software on your computer. If you are using thin client, or are not allowed to install document reader of particular type, this application may come in hand for you. Simply upload your document, and Docureader.top will transform it into readable format in a few seconds. Why choose Docureader.top?

  1. Unlimited sharing - you can upload document of any size. If we are able to convert it into readable format, you have it here - saved for later or immediate reading
  2. Cross-platform - no compromised when reading your document. We support most of modern browers without the need of installing any of external plugins. If your device can oper a browser - then you can read any document on it
  3. Simple uploading - no need to register. Just enter your email, title of document and select the file, we do the rest. Once the document is ready for you, you will receive automatic email from us.

Previous 10

Next 10