Effect of Switching From Cigarette Smoking to the Use of IQOS on Periodontitis Treatment Outcome

A 6-month Randomized, Controlled, Open-label, 2-arm Parallel Group, Multicenter Study to Evaluate the Effect of Switching From Cigarette Smoking to the Use of IQOS in Smokers With Generalized Chronic Periodontitis on the Response to Mechanical Periodontal Treatment and Oral Health Status.

The purpose of this study was to demonstrate in patients with generalized chronic periodontitis that switching from cigarette smoking to using IQOS improves the response to periodontal therapy and the overall oral health status compared to continuing cigarette smoking.

Note: "IQOS" is the Tobacco Heating System (THS) with Marlboro Heatsticks, marketed in Japan under the brand name IQOS

Study Overview

• Status: Completed
• Conditions: Periodontal Diseases; Gingival Diseases; Chronic Periodontitis; Smoking, Cigarette; Periodontal Pocket; Tooth Mobility
• Intervention / Treatment: Other: IQOS; Other: Cigarette

Detailed Description

This was a randomized, controlled, open-label, 2-arm, parallel group ambulatory study with the randomization stratified by daily cigarette consumption over the month (30 days) prior to Visit 1 (10-19 cigarettes/day vs. > 19 cigarettes/day) and disease severity recorded at Visit 1 (< 5 mm Pocket Depth [PD] vs. ≥ 5 mm PD) based on the most severely diseased tooth, in smokers with generalized chronic periodontitis who are randomized to either switch from cigarette smoking to IQOS use or continuing cigarette smoking.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 810-0001
    • Kimura Dental Clinic
  • Fukuoka, Japan, 810-0001
    • Yamashita Dental Office
  • Fukuoka, Japan, 810-0001
    • Yasumasu Dental Office
  • Fukuoka, Japan, 811-1302
    • Tsukiyama Dental Clinic
  • Fukuoka, Japan, 812-0011
    • Yoshida Shigeru Dental Office
  • Kagoshima, Japan, 890-0053
    • Yamashita Dental Clinic
  • Kagoshima, Japan, 892-0844
    • Heart Dental Clinic
  • Kumamoto, Japan, 860-0855
    • Higashi Dental Office
  • Chiba
    • Futtsu, Chiba, Japan, 293-0001
      • Mase Dental Clinic
    • Narashino, Chiba, Japan, 275-0016
      • Tsudanuma Olive Dental Clinic
  • Fukuoka
    • Miyako, Fukuoka, Japan, 800-0323
      • Matsunobu Dental Office
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0023
      • Taniguchi Dental Clinic
  • Ibaraki
    • Chikusei, Ibaraki, Japan, 308- 0031
      • Takano Dental Clinic
    • Tsukuba, Ibaraki, Japan, 305-0834
      • Tsukuba Healthcare Dental Clinic
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 210-0822
      • AOI Universal Hospital
  • Kumamoto
    • Uki, Kumamoto, Japan, 869-0521
      • Yoshinaga Dental Office
  • Saitama
    • Kawaguchi, Saitama, Japan, 332-0016
      • Yoshino Dental Clinic
    • Tokorozawa, Saitama, Japan, 359-1146
      • Saida Dental Clinic
  • Tokyo
    • Bunkyō, Tokyo, Japan, 113-0033
      • Sakai Dental Clinic
    • Chiyoda, Tokyo, Japan, 102-0074
      • Kudan Dental Clinic
    • Chōfu, Tokyo, Japan, 182-0024
      • Yano Dental Clinic
    • Chūō, Tokyo, Japan, 103-0027
      • Nikaido Dental Clinic
    • Setagaya, Tokyo, Japan, 157-0072
      • Mune Dental Clinic
    • Shinjuku, Tokyo, Japan, 160-0023
      • Kikuchi Dental Clinic
    • Toshima, Tokyo, Japan, 171-0043
      • Miyata Dental Clinic
  • Toyama
    • Himi, Toyama, Japan, 935-0015
      • Kato Dental Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Patient is aged ≥ 30 years old.
2. Patient has smoked on average at least 10 commercially available cigarettes per day for at least 5 years
3. Patient has generalized chronic periodontitis (i.e., more than 30% of diseased teeth with a PD ≥ 4 mm).

Main Exclusion Criteria:

1. Patient has self-reported history of diagnosed systemic diseases (e.g., stroke or acute cardiovascular event within the last 5 years, diabetes, active cancer).
2. Patient received root planing therapy within the 6 months prior to Visit 1.
3. Patient received surgical periodontal therapy within 3 years prior to Visit
4. Patient was treated within the 3 months prior to Visit 1 with systemic antibiotics or was treated with topical antibiotics applied in the mouth.
5. Continuous systemic use of steroidal or non-steroidal anti-inflammatory drugs for more than 20 days during the past 30-day period (except for low dose aspirin, i.e., ≤300 mg).
6. Female patients who are pregnant, breast-feeding, or planning a pregnancy within the course of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IQOS arm; ~86 patients, switching from cigarette smoking to IQOS use.	Other: IQOS; Patients will switch from cigarette smoking to ad libitum IQOS use.
Active Comparator: Cigarette arm; ~86 patients, continuing cigarette smoking.	Other: Cigarette; Patients will continue to smoke cigarettes ad libitum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periodontal Pocket Depth (PD) Change From Baseline at 6 Months	Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm)	Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	At 3 months
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm)	Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Mean CAL change from baseline will be measured in sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	At 3 months and 6 months
Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics	Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	From baseline to 3 months and 6 months
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics	Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Mean CAL change from baseline will be measured in sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	From baseline to 3 months and 6 months
Full-mouth Periodontal PD Change Over Time.	Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Change in mean full-mouth PD will be measured, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	From baseline to 3 months and 6 months
Full-mouth Clinical Attachment Level (CAL) Over Time.	Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Change in mean full-mouth CAL will be measured, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.	From baseline to 3 months and 6 months
Peridontal PD Reduction.	Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean PD change will be measured in sites with initial PD < 4 mm, and with initial PD of 4 mm to <5 mm, 5 mm to < 6 mm, 6 mm to < 7 mm and ≥ 7 mm.	From baseline to 3 months and 6 months
Clinical Attachment Level Improvement	Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Mean CAL change will be measured in sites with initial PD < 4 mm, and with initial PD of 4 mm to <5 mm, 5 mm to < 6 mm, 6 mm to < 7 mm and ≥ 7 mm.	From baseline to 3 months and 6 months
Number of Periodontally Diseased Sites.	Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Any change will be recorded in the number of periodontally diseased sites with Pocket Depth (PD) < 4 mm, with PD 4 mm to < 5mm, with PD 5 mm to < 6 mm , with PD 6 mm to < 7 mm and with PD ≥ 7 mm. PD is the distance from the gingival margin to which a probe penetrates into the pocket.	From baseline to 3 months and 6 months
Gingival Inflammation	Gingival inflammation will be measured by calculating the gingival index (GI) score for each target tooth. The gingival index (GI) scores each site on a 0 to 3 scale, with 0 being normal and 3 being severe inflammation characterized by edema, redness, swelling, and spontaneous bleeding.	From baseline to 3 months and 6 months
Tooth Mobility	Tooth mobility will be graded according to Miller's mobility index (MMI), which is the most widely accepted method for routine clinical examinations of tooth mobility. The tooth is held between the metallic handles of two instruments and moved in the buccolingual or buccopalatal direction, and the moved distance is visually estimated by the person conducting the examination. Grade 0: Physiologic movement within 0.2 mm; Grade 1: Slight mobility, tooth can be moved 0.2 - 1 mm labiolingually; Grade 2: Moderate mobility, tooth can be moved 1 - 2 mm labiolingually or mesiodistally; Grade 3: Severe mobility, tooth can be moved more than 2 mm labiolingually or mesiodistally, or ability to depress the tooth in a vertical direction.	From baseline to 3 months and 6 months
Presence of Plaque on Tooth Surfaces in Full Mouth	Plaque will be measured using the plaque control record (PCR) percentage.	From baseline to 3 months and 6 months
Inflammatory Status in Periodontal Pockets	Gum inflammation was measured using percentage of teeth bleeding on probing (BOP). BOP in full mouth was measured to assess inflammatory status in the pocket and was assessed as YES or NO of bleeding at 6 sites per tooth. Gently probing (approximately 20 g pressure), the bleeding site within 30 seconds was assessed as YES.	From baseline to 3 months and 6 months
Concentrations of Urinary Nicotine Equivalents (NEQ)	This biomarker of exposure to a tobacco smoke constituent will be measured in patients who switch to IQOS use and patients who continue cigarette smoking. Concentrations measured in urine and expressed as concentration adjusted for creatinine (mg/g creat).	From baseline to 3 months and 6 months
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)	This biomarker of exposure to a tobacco smoke constituent will be measured in patients who switch to IQOS use and patients who continue cigarette smoking. Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).	From baseline to 3 months and 6 months
Concentrations of 2-cyanoethylmercapturic Acid (CEMA)	This biomarker of exposure to a tobacco smoke constituent will be measured in patients who switch to IQOS use and patients who continue cigarette smoking. Concentrations measured in urine and expressed as concentration adjusted for creatinine (ng/mg creat).	From baseline to 3 months and 6 months
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking.	Self-reported use of tobacco or nicotine containing products will be measured over the study in patients switching to IQOS use and patients who continue cigarette smoking.	From baseline to 6 months

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.

Publications and helpful links

General Publications

• Pouly S, Ng WT, Benzimra M, Soulan A, Blanc N, Zanetti F, Picavet P, Baker G, Haziza C. Effect of Switching to the Tobacco Heating System Versus Continued Cigarette Smoking on Chronic Generalized Periodontitis Treatment Outcome: Protocol for a Randomized Controlled Multicenter Study. JMIR Res Protoc. 2021 Jan 18;10(1):e15350. doi: 10.2196/15350.
• Effect of switching from cigarette smoking to the use of the tobacco heating system on periodontitis treatment outcome: Periodontal parameter results from a multicenter Japanese study Authors: Pouly, Sandrine; Ng, Wee Teck; Blanc, Nicolas; Hession, Paul; Zanetti, Filippo; Battey, James N. D.; de La Bourdonnaye, Guillaume; Heremans, Annie; Haziza, Christelle Journal Title: Frontiers in dental medicine Publication Date: 7/22/2022 Volume: 3 DOI: 10.3389/fdmed.2022.915079

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2017
• Primary Completion (Actual): December 21, 2018
• Study Completion (Actual): June 12, 2019

Study Registration Dates

• First Submitted: November 23, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 7, 2017

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Smoking; Oral Health; Cigarette; Reduced risk product; Tobacco heating system; THS; Modified risk tobacco product; Clinical attachment level
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Periodontitis; Periodontal Diseases; Chronic Periodontitis; Periodontal Pocket; Gingival Diseases; Tooth Mobility
• Other Study ID Numbers: P1-OHS-01-JP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No