Comparative Evaluation of Ketoprofen Gel Alone and in Combination with Doxycycline Gel as Local Drug Delivery in the Treatment of Chronic Periodontitis among Smokers and Non-Smokers: A Randomized Clinical Trial

ABSTRACT

Background and Objective:

Often, the treatment goals for chronic periodontitis in smokers are not achieved only by scaling and root planing (SRP) as non-surgical periodontal therapy. Adjunctive therapy such as local drug delivery (LDD) can be carried out in an attempt to reduce the need for periodontal surgery. The study was carried out to determine the efficacy of subgingivally delivered ketoprofen (K) + doxycycline (D) gel and compare it with that of subgingivally delivered ketoprofen (K) gel alone as an adjunct to SRP in smokers and non-smoker patients having chronic periodontitis.

Materials and Methods:

Twelve patients in the non-smoker group and nine patients in the smoker group having chronic periodontitis with ≥4-mm pocket depth in at least three adjacent teeth in each quadrant were recruited for the study. The quadrants were randomized into K alone and K + D subgroups. 2.5% ketoprofen gel and 2.5% ketoprofen + 3% doxycycline gel were delivered into designated sites after SRP, and the sites were secured using periodontal dressing. Plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and relative attachment level (RAL) were recorded at baseline and 3 months.

Results:

At 3 months follow-up, both the groups showed significant improvement in PI, BOP, PPD, and RAL (P < 0.05). K + D showed a significantly greater reduction of PI, BOP, PPD, and RAL in both smokers and non-smokers than K alone (P < 0.05). Non-smokers responded significantly better than smokers for PI, BOP, PPD, and RAL with both treatment modalities (P < 0.05).

Conclusion:

The results indicate that smokers and non-smokers demonstrate better clinical outcomes by using K + D LDD as an adjunct to SRP. Moreover, non-smokers responded better to both modalities than smokers.

INTRODUCTION

Chronic periodontitis is the second most prevalent dental disease according to the Global Burden of Disease Study 2017 and progresses in a slow-to-moderate degree of disease development, with intervals of more rapid destruction. Periodontal treatment aims at pocket reduction and restoration of gingival health. The primary treatment approach is non-surgical periodontal therapy followed by surgical periodontal therapy when indicated. Only subgingival scaling and root planing (SRP) can achieve a little clinical attachment gain.[1] Hence, for reducing the need for surgical treatment, certain adjuncts can be used with SRP, such as local or systemic antimicrobial therapy, host modulation therapy, LASER debridement, and photodynamic therapy. The aim of the study was to determine the efficacy of subgingivally delivered ketoprofen gel alone and its synergistic effect in combination with doxycycline gel as an adjunct to SRP in smokers and non-smoker patients having chronic periodontitis.

MATERIALS AND METHODS

This randomized controlled clinical study with split-mouth design was conducted in the Department of Periodontology, Manubhai Patel Dental College and Oral Research Center, Vadodara, Gujarat, India on a total of 21 patients (12 non-smokers and 9 smokers) having chronic periodontitis on an outpatient basis who had given informed consent toward the treatment. The trial was prospectively registered with Bhavnagar University Ethical Committee (reference number: REF/BUETHICS/MPDC_168/PERIO-20/19) and Clinical Trials Registry of India [CTRI Reg. no.: CTRI/2020/03/024280]. Systemically healthy patients aged ≥25–60 years with a minimum of 20 natural teeth, probing depth (PD) of ≥4 mm, and clinical attachment loss (CAL) of ≥1 mm in at least three sites per quadrant in all quadrants of the mouth were selected for the study. They were categorized based on smoking status as smokers group having subjects smoking ≥1 cigarette/bidi per day for at least 1 year, and the non-smokers group having subjects who have never smoked cigarettes or any other form of tobacco.

Method of randomization

Patients were grouped based on their smoking status, and the quadrants were randomized into subgroups by using the coin test.

• Subgroup 1: Patients underwent SRP followed by subgingivally delivered 2.5% ketoprofen + 3% doxycycline gel (K + D).

• Subgroup 2: Patients underwent SRP followed by subgingivally delivered 2.5% ketoprofen gel (K).

METHODOLOGY

Formulation of drugs used

For local drug delivery (LDD), nano-emulgels of 2.5% ketoprofen + 3% doxycycline hyclate (KTP + DOX) and 2.5% ketoprofen (KTP) gel were prepared as controlled release formulation with the help of the Department of Pharmaceutics, Faculty of Pharmacy, MS University, Vadodara. 2.5% ketoprofen gel was prepared as in situ mucoadhesive gel by using the formulation given by Srivastava et al.[2] in 2014. 3% doxycycline formulation was adapted from Chadha A et al.[3] 2012. This gel was then added to ketoprofen gel to achieve a final concentration of 3% doxycycline and 2.5% ketoprofen gel while stirring continuously by mechanical magnetic stirring.

Method of standardization

Customized acrylic stents were prepared on study models for each patient, and vertical grooves were made on the stent at each site of measurement for standardization. Hu Friedy^® UNC-15 probe was used for measurements. All the patients were treated by a single clinician. The parameters were recorded at baseline and 3 months by a calibrated examiner to whom the categorization of sites was blinded.

Procedure

All the patients were explained about the entire treatment protocol and possible side effects of each drug in vernacular language, and written informed consent was taken prior to recruitment in the trial. After recording the baseline parameters, each patient underwent single-sitting SRP using hand and ultrasonic instruments. The teeth to be treated were isolated, and in situ gel corresponding to the quadrant subgroup was delivered into the pocket on both buccal and palatal/lingual sides till it overflowed by using an insulin syringe-blunt needle. Following the placement of gels, sites were secured using a periodontal pack. Patients were recalled at 1-week interval for periodontal pack removal. They were instructed to inform any untoward effect of any drugs used. Patients were recalled at 3 months for follow-up measurements. The primary outcomes were probing pocket depth (PPD) and relative attachment level (RAL), and the secondary outcomes were plaque index (PI) (Silness and Loe, 1964)[4] and gingival bleeding index (Ainamo and Bay, 1975)[5] [Figure 1].

Figure 1.

Periodontal probing using a stent and UNC 15 probe and placement of gel

Results were calculated using Statistical Package for Social Sciences version 20.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics was used for calculating the mean, standard deviation, and confidence interval of data. Paired t-test and independent t-test were used for comparative analysis.

RESULTS AND DISCUSSION

Out of 21 patients, eight were females and 13 were males. There was no significant difference in baseline parameters between the groups as well as subgroups. Changes in clinical parameters were noted and they were significant. Table 1 depicts the results obtained in smokers.

Table 1.

Evaluating the baseline and follow-up parameters and comparing the intergroup and intragroup changes in smokers

	Ketoprofen + Doxycycline				Ketoprofen				P (∆t1 and ∆t2)
	Baseline (t0)	Follow up (t1)	∆t1=t0 - t1	P	Baseline (t0)	Follow up (t1)	∆t2=t0 - t1	P
PI	1.51±0.23	1.10±0.22	0.41±0.02	0.000	1.49±0.19	1.12±0.18	0.37±0.03	0.000	0.002
GI (%)	100±0.00	33±8	67±8	0.000	100±0.00	44±12	55±12	0.000	0.022
PPD (mm)	4.15±0.39	2.51±0.20	1.63±0.29	0.000	4.03±0.40	2.82±0.38	1.20±0.10	0.000	0.000
RAL (mm)	6.78±1.28	5.26±1.26	1.16±0.12	0.000	6.80±1.29	5.79±1.24	1.01±0.15	0.000	0.000

A significant clinical improvement (P < 0.05) was seen in PI (1.48 ± 0.12 to 0.91 ± 0.19, P = 0.00), gingival bleeding index (98 ± 4% to 40 ± 8%, P = 0.00), PD (4.35 ± 0.59 mm to 2.68 ± 0.58 mm, P = 0.00), and RAL (7.24 ± 1.1 4 mm to 5.03 ± 1.18 mm, P = 0.00) in the K + D subgroup. In the K subgroup, all clinical parameters, namely PI (1.49 ± 0.13 to 0.98 ± 0.19, P = 0.00), gingival bleeding index (100 ± 0.00% to 0.52 ± 0.15, P = 0.00), PD (4.33 ± 0.63 mm to 2.84 ± 0.52 mm, P = 0.00), and RAL (7.18 ± 1.07 mm to 5.99 ± 1.07 mm, P = 0.00) improved significantly (P < 0.05). The change in clinical parameters from baseline to follow-up was noted as Δt₁ in the case of the K + D subgroup and Δt₂ in the K subgroup. The mean change in each parameter of all subjects was calculated and tabulated. There was a significant difference between mean change in PPD (K + D = 1.68 ± 0.16 mm, K = 1.48 ± 0.19 mm, P = 0.002) and RAL (K + D = 2.21 ± 0.07 mm, K = 1.18 ± 0.05 mm, P = 0.00) in which K + D was better than K alone (P < 0.05). The secondary outcomes PI (K + D = 0.57 ± 0.10, K = 0.51 ± 0.11, P = 0.128) and gingival bleeding index (K + D = 58 ± 8%, K = 47 ± 15%, P = 0.104) did not show significant difference (P > 0.05).

Non-smokers responded significantly better than smokers to ketoprofen alone in PI reduction (NS: 0.51 ± 0.11 vs. S: 0.37 ± 0.03; P = 0.002), PD reduction (NS: 1.48 ± 0.19 vs. S: 1.20 ± 0.10; P = 0.001) and relative attachment gain (NS: 1.18 ± 0.05 mm vs. S: 1.01 ± 0.15 mm; P = 0.002). There was a non-significant (P = 0.198) difference between both groups for bleeding index, with smokers showing greater bleeding reduction (55 ± 12%) than non-smokers (47 ± 15%).

CONCLUSION

The results of the study demonstrated a significant effect of smoking on non-surgical periodontal treatment. However, the use of LDD by anti-inflammatory alone or in combination with an antimicrobial agent can prove as a valuable adjunct for short-term improvement in periodontal parameters of chronic periodontitis cases regardless of smoking. The use of LDD can be a plausible option for reducing surgical treatment need in smokers.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.