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Subgingival application of a doxycycline-containing gel slightly adds to the clinical benefits of scaling and root planing
A RT I C L E A N A LY S I S & E VA LUAT I O N : T H E R A PY Subgingival application of a doxycycline-containing gel slightly adds to the clinical benefits of scaling and root planing Original Article:
Eickholz P, Kim TS, Bürklin T, Schacher B, Renggli HH, Schaecken MT, Holle R, Kübler A, Ratka-Krüger P. Non-surgical periodontal therapy with adjunctive topical doxycycline: a double-blind randomized controlled multicenter study. (I). Study design and clinical results. J Clin Periodontol 2002;29:108-17.
• Level of Evidence: • Purpose/Question:
1b
• Source of Funding: • Type of Study/Design:
Ivoclar Vivadent HAG, Schaan, Liechtenstein
Evaluation of the clinical effect of the subgingival application of a 15% doxycycline hyclate–containing gel when used as an adjunct to nonsurgical periodontal therapy
Randomized controlled multicenter trial
S U M M A RY SUBJECTS A total of 111 patients with periodontitis (69 females; 42 males) from the ages of 23 to 71 years of age were enrolled. Of these, 110 completed the 3-month followup and 108 completed the entire 6-month study. Patients were enrolled in 3 participating university-based centers (Heidelberg, Frankfurt, and Nijmegen). Some patients had chronic (“adult”) periodontitis (n = 89) whereas others had aggressive (“early onset”) periodontitis (n = 21).
TREATMENT In this split-mouth study all patients received the following treatment on 3 single-rooted teeth in 3 separate quadrants: scaling and root planing (SRP),
SRP + subgingival placement of the gel vehicle (polyethylene glycol–lactid/glycolid copolymer; VEH group), and SRP + 15% doxycycline hyclate in the gel (DOXI group).
MAIN OUTCOME MEASURE: The main outcome measure was change in vertical relative attachment level (RAL–V) as measured with a manual periodontal probe. RAL–V is the distance from a notch on a plastic reference splint to the base of the probeable gingival crevice. Change in probing depth (PD) was used as a secondary outcome measure. Measurements were recorded at baseline and 3 and 6 months after treatment. A difference of 0.5 mm in PD reduction or RAL-V gain
between test and control was considered a clinically relevant difference between treatments.
MAIN RESULTS On the basis of analysis of clinical data from the baseline and 6month exams, application of adjunctive doxycycline gel resulted in statistically significant reductions in PD compared with SRP alone or SRP + gel vehicle (SRP: –2.4 ± 1.4 mm, VEH: –2.7 ± 1.6 mm, DOXI: –3.1 ± 1.2 mm; SRP vs DOXI: P = .0001, VEH vs DOXI: P = .0066). At 6 months, statistically significant gains in RAL–V were noted for the doxycyclinetreated group (SRP: 1.6 ± 1.9 mm, VEH: 1.6 ± 2.2 mm, DOXI: 2.0 ± 1.7 mm; SRP vs DOXI: P = .027, VEH vsw DOXI: P = .038).
J Evid Base Dent Pract 2002;2:277-8 © 2002 Mosby, Inc. All rights reserved. doi:10.1067/med.2002.130085
277
C O M M E N T A RY CONCLUSIONS Adjunctive subgingival application of a gel containing 15% doxycycline provided statistically significant gains in RAL–V and reductions in PD compared with SRP alone or SRP + gel. Mean differences in the outcome measures between the treatment groups were small.
ANALYSIS The main results of this study are consistent with the general findings of other multicenter trials on the subgingival placement of antimicrobial delivery systems as adjuncts to SRP.1-3 In these studies, small but statistically significant average reductions in probing depth and gains in clinical attachment were found. Although the trial appears to be carefully conducted, for a multicenter effort the study population is small (n = 110), in that other multicenter studies included from 411-748 participants.1-3 In addition, the study population was somewhat heterogeneous since approximately 19% of the participants had “early onset” periodontitis and 81% had chronic “adult” periodontitis. The criteria used for the designations of “early onset” periodontitis and chronic “adult” periodontitis are not clear. More-
Table 5a. Change in clinical parameters (RAL-V, PPD) after 3 and 6 months
RAL-V/mm 3 months (110) 6 months (108) PD mm 3 months (110) 6 months (108)
SRP
VEH
DOXI
P value
1.8 ± 1.7 1.6 ± 1.9
1.7 ± 1.9 1.6 ± 2.2
2.0 ± 1.6 2.0 ± 1.7
0.30 0.057
–2.5 ± 1.6 –2.4 ± 1.4
–2.6 ± 1.5 –2.7 ± 1.6
–2.9 ± 1.3 –3.1 ± 1.2
0.03 0.002
Reviewer’s note: P-values calculated by repeated measures ANOVA (Adapted from Eickholz P, Kim TS, Bürklin T, Schacher B, Renggli HH, Schaecken MT, et al. J Clin Periodontol 2002;29:108-17. By permission.)
• Reviewer:
278 Eickholz et al
over, confining the study to single-rooted teeth limits any clinical conclusions that can be drawn from the results. Finally, apparently some of the patients received periodontal surgery around teeth not selected as test sites. The impact of this surgical intervention, performed approximately 1 week after insertion of the subgingival gels, is not specified or included in the analysis. The number of the patients who had periodontal surgery is not mentioned. Despite these design problems, the results suggest that a larger multicenter study of the safety and efficacy of the 15% doxycycline gel as an adjunct to SRP is warranted. REFERENCES 1. Jeffcoat MK, Bray KS, Ciancio SG, Dentino AR, Fine DH, Gordon JM, et al. Adjunctive use of a subgingival controlledrelease chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone. J Periodontol 1998;69:989-97. 2. Garrett S, Johnson L, Drisko CH, Adams DF, Bandt C, Beiswanger B, et al. Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. J Periodontol 1999;70:490-503. 3. Williams RC, Paquette DW, Offenbacher S, Adams DF, Armitage GC, Bray K, et al. Treatment of periodontitis by local administration of minocycline microspheres: A controlled trial. J Periodontol 2001;72:1535-44.
Table 5b. Pairwise comparisons of change of clinical parameters (RAL-V, PPD) after 3 and 6 months
RAL-V/mm 3 months (110) 6 months (108) PPD/mm 3 months (110) 6 months (108)
DOXI/SRP
P value
DOXI/VEH
P value
0.22 ± 1.81 0.38 ± 1.78
0.21 0.027
0.25 ± 1.76 0.37 ± 1.84
0.15 0.038
0.43 ± 1.62 0.67 ± 1.58
0.006 0.0001
0.29 ± 1.77 0.44 ± 1.67
0.085 0.0066
(Adapted from Eickholz P, Kim TS, Bürklin T, Schacher B, Renggli HH, Schaecken MT, et al. J Clin Periodontol 2002;29:108-17. By permission.)
Gary Armitage, DDS, MS,University of California at San Francisco
Journal of Evidence-Based Dental Practice December 2002
Eickholz P, Kim TS, Bürklin T, Schacher B, Renggli HH, Schaecken MT, Holle R, Kübler A, Ratka-Krüger P. Non-surgical periodontal therapy with adjunctive topical doxycycline: a double-blind randomized controlled multicenter study. (I). Study design and clinical results. J Clin Periodontol 2002;29:108-17.
• Level of Evidence: • Purpose/Question:
1b
• Source of Funding: • Type of Study/Design:
Ivoclar Vivadent HAG, Schaan, Liechtenstein
Evaluation of the clinical effect of the subgingival application of a 15% doxycycline hyclate–containing gel when used as an adjunct to nonsurgical periodontal therapy
Randomized controlled multicenter trial
S U M M A RY SUBJECTS A total of 111 patients with periodontitis (69 females; 42 males) from the ages of 23 to 71 years of age were enrolled. Of these, 110 completed the 3-month followup and 108 completed the entire 6-month study. Patients were enrolled in 3 participating university-based centers (Heidelberg, Frankfurt, and Nijmegen). Some patients had chronic (“adult”) periodontitis (n = 89) whereas others had aggressive (“early onset”) periodontitis (n = 21).
TREATMENT In this split-mouth study all patients received the following treatment on 3 single-rooted teeth in 3 separate quadrants: scaling and root planing (SRP),
SRP + subgingival placement of the gel vehicle (polyethylene glycol–lactid/glycolid copolymer; VEH group), and SRP + 15% doxycycline hyclate in the gel (DOXI group).
MAIN OUTCOME MEASURE: The main outcome measure was change in vertical relative attachment level (RAL–V) as measured with a manual periodontal probe. RAL–V is the distance from a notch on a plastic reference splint to the base of the probeable gingival crevice. Change in probing depth (PD) was used as a secondary outcome measure. Measurements were recorded at baseline and 3 and 6 months after treatment. A difference of 0.5 mm in PD reduction or RAL-V gain
between test and control was considered a clinically relevant difference between treatments.
MAIN RESULTS On the basis of analysis of clinical data from the baseline and 6month exams, application of adjunctive doxycycline gel resulted in statistically significant reductions in PD compared with SRP alone or SRP + gel vehicle (SRP: –2.4 ± 1.4 mm, VEH: –2.7 ± 1.6 mm, DOXI: –3.1 ± 1.2 mm; SRP vs DOXI: P = .0001, VEH vs DOXI: P = .0066). At 6 months, statistically significant gains in RAL–V were noted for the doxycyclinetreated group (SRP: 1.6 ± 1.9 mm, VEH: 1.6 ± 2.2 mm, DOXI: 2.0 ± 1.7 mm; SRP vs DOXI: P = .027, VEH vsw DOXI: P = .038).
J Evid Base Dent Pract 2002;2:277-8 © 2002 Mosby, Inc. All rights reserved. doi:10.1067/med.2002.130085
277
C O M M E N T A RY CONCLUSIONS Adjunctive subgingival application of a gel containing 15% doxycycline provided statistically significant gains in RAL–V and reductions in PD compared with SRP alone or SRP + gel. Mean differences in the outcome measures between the treatment groups were small.
ANALYSIS The main results of this study are consistent with the general findings of other multicenter trials on the subgingival placement of antimicrobial delivery systems as adjuncts to SRP.1-3 In these studies, small but statistically significant average reductions in probing depth and gains in clinical attachment were found. Although the trial appears to be carefully conducted, for a multicenter effort the study population is small (n = 110), in that other multicenter studies included from 411-748 participants.1-3 In addition, the study population was somewhat heterogeneous since approximately 19% of the participants had “early onset” periodontitis and 81% had chronic “adult” periodontitis. The criteria used for the designations of “early onset” periodontitis and chronic “adult” periodontitis are not clear. More-
Table 5a. Change in clinical parameters (RAL-V, PPD) after 3 and 6 months
RAL-V/mm 3 months (110) 6 months (108) PD mm 3 months (110) 6 months (108)
SRP
VEH
DOXI
P value
1.8 ± 1.7 1.6 ± 1.9
1.7 ± 1.9 1.6 ± 2.2
2.0 ± 1.6 2.0 ± 1.7
0.30 0.057
–2.5 ± 1.6 –2.4 ± 1.4
–2.6 ± 1.5 –2.7 ± 1.6
–2.9 ± 1.3 –3.1 ± 1.2
0.03 0.002
Reviewer’s note: P-values calculated by repeated measures ANOVA (Adapted from Eickholz P, Kim TS, Bürklin T, Schacher B, Renggli HH, Schaecken MT, et al. J Clin Periodontol 2002;29:108-17. By permission.)
• Reviewer:
278 Eickholz et al
over, confining the study to single-rooted teeth limits any clinical conclusions that can be drawn from the results. Finally, apparently some of the patients received periodontal surgery around teeth not selected as test sites. The impact of this surgical intervention, performed approximately 1 week after insertion of the subgingival gels, is not specified or included in the analysis. The number of the patients who had periodontal surgery is not mentioned. Despite these design problems, the results suggest that a larger multicenter study of the safety and efficacy of the 15% doxycycline gel as an adjunct to SRP is warranted. REFERENCES 1. Jeffcoat MK, Bray KS, Ciancio SG, Dentino AR, Fine DH, Gordon JM, et al. Adjunctive use of a subgingival controlledrelease chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone. J Periodontol 1998;69:989-97. 2. Garrett S, Johnson L, Drisko CH, Adams DF, Bandt C, Beiswanger B, et al. Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. J Periodontol 1999;70:490-503. 3. Williams RC, Paquette DW, Offenbacher S, Adams DF, Armitage GC, Bray K, et al. Treatment of periodontitis by local administration of minocycline microspheres: A controlled trial. J Periodontol 2001;72:1535-44.
Table 5b. Pairwise comparisons of change of clinical parameters (RAL-V, PPD) after 3 and 6 months
RAL-V/mm 3 months (110) 6 months (108) PPD/mm 3 months (110) 6 months (108)
DOXI/SRP
P value
DOXI/VEH
P value
0.22 ± 1.81 0.38 ± 1.78
0.21 0.027
0.25 ± 1.76 0.37 ± 1.84
0.15 0.038
0.43 ± 1.62 0.67 ± 1.58
0.006 0.0001
0.29 ± 1.77 0.44 ± 1.67
0.085 0.0066
(Adapted from Eickholz P, Kim TS, Bürklin T, Schacher B, Renggli HH, Schaecken MT, et al. J Clin Periodontol 2002;29:108-17. By permission.)
Gary Armitage, DDS, MS,University of California at San Francisco
Journal of Evidence-Based Dental Practice December 2002