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

• ClinicalTrials.gov Identifier: NCT03364751
• Recruitment Status: Completed
• First Posted: December 7, 2017
• Results First Posted: February 18, 2021
• Last Update Posted: January 30, 2023
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Tracking Information

• First Submitted Date: November 23, 2017
• First Posted Date: December 7, 2017
• Results First Submitted Date: November 11, 2020
• Results First Posted Date: February 18, 2021
• Last Update Posted Date: January 30, 2023
• Actual Study Start Date: November 7, 2017
• Actual Primary Completion Date: December 21, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 27, 2021)

Periodontal Pocket Depth (PD) Change From Baseline at 6 Months [ Time Frame: 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.

Original Primary Outcome Measures (submitted: December 1, 2017)

Periodontal pocket depth (PD) reduction. [ Time Frame: From baseline to 6 months ]

Mean Periodontal PD reduction 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.

Current Secondary Outcome Measures (submitted: January 27, 2021)

• Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm) [ Time Frame: At 3 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.
• Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) [ Time Frame: At 3 months and 6 months ]
  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.
• Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics [ Time Frame: From baseline to 3 months and 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.
• Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Full-mouth Periodontal PD Change Over Time. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Full-mouth Clinical Attachment Level (CAL) Over Time. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Peridontal PD Reduction. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Clinical Attachment Level Improvement [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Number of Periodontally Diseased Sites. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Gingival Inflammation [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Tooth Mobility [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Presence of Plaque on Tooth Surfaces in Full Mouth [ Time Frame: From baseline to 3 months and 6 months ]
  Plaque will be measured using the plaque control record (PCR) percentage.
• Inflammatory Status in Periodontal Pockets [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Concentrations of Urinary Nicotine Equivalents (NEQ) [ Time Frame: From baseline to 3 months and 6 months ]
  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).
• Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) [ Time Frame: From baseline to 3 months and 6 months ]
  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).
• Concentrations of 2-cyanoethylmercapturic Acid (CEMA) [ Time Frame: From baseline to 3 months and 6 months ]
  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).
• Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. [ Time Frame: From baseline to 6 months ]
  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.

Original Secondary Outcome Measures (submitted: December 1, 2017)

• Periodontal pocket depth (PD) change over time. [ Time Frame: From baseline to 3 months ]
  Mean Periodontal PD change 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.
• Clinical Attachment Level (CAL) change over time. [ Time Frame: From baseline to 3 months and 6 months ]
  Mean CAL change 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.
• Full-mouth periodontal PD change over time. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Full-mouth Clinical Attachment Level (CAL) over time. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Peridontal PD reduction. [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Clinical Attachment Level improvement. [ Time Frame: From baseline to 3 months and 6 months ]
  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
• Number of periodontally diseased sites. [ Time Frame: From baseline to 3 months and 6 months ]
  Any change will be recorded in the number of diseased sites with 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.
• Gingival inflammation [ Time Frame: From baseline to 3 months and 6 months ]
  Gingival inflammation will be measured by calculating the gingival index (GI) score for each target tooth.
• Tooth mobility [ Time Frame: From baseline to 3 months and 6 months ]
  Tooth mobility will be measured using Miller's classification (grade 0 to grade 3).
• Presence of plaque on tooth surfaces in full mouth [ Time Frame: From baseline to 3 months and 6 months ]
  Plaque will be measured using the plaque control record (PCR) percentage.
• Inflammatory status in periodontal pockets [ Time Frame: From baseline to 3 months and 6 months ]
  PD inflammation will be measured with bleeding on probing (BOP) percentage.
• Urinary nicotine equivalents (NEQ) [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Total 4-[methylnitrosamino]-1-[3-pyridyl]-1- butanol (NNAL) [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• 2-cyanoethylmercapturic acid (CEMA) [ Time Frame: From baseline to 3 months and 6 months ]
  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.
• Use of tobacco or nicotine-containing products in patients switching to IQOS use and patients who continue cigarette smoking. [ Time Frame: From baseline to 6 months ]
  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.
• Safety during the study [ Time Frame: For the duration of the study (6 months) ]
  To monitor safety over the duration of the study, the following parameters will be measured: Incidence of adverse events (AEs)/serious adverse events (SAEs), including AEs related to device events, and device events, including device malfunction/misuse.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Switching From Cigarette Smoking to the Use of IQOS on Periodontitis Treatment Outcome
• Official Title: 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.

Brief Summary

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

• 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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Investigator)
Masking Description:

The Dentist (Investigator) or Dental Hygienist performing the periodontal assessments will be blinded to the arm allocation.

Primary Purpose: Other

Condition

• Periodontal Diseases
• Chronic Periodontitis
• Periodontal Pocket
• Tooth Mobility
• Gingival Diseases
• Smoking, Cigarette

Intervention

• Other: IQOS
  Patients will switch from cigarette smoking to ad libitum IQOS use.
• Other: Cigarette
  Patients will continue to smoke cigarettes ad libitum.

Study Arms

• Active Comparator: IQOS arm
  ~86 patients, switching from cigarette smoking to IQOS use.
  Intervention: Other: IQOS
• Active Comparator: Cigarette arm
  ~86 patients, continuing cigarette smoking.
  Intervention: Other: Cigarette

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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 27, 2021): 179
• Original Estimated Enrollment (submitted: December 1, 2017): 172
• Actual Study Completion Date: June 12, 2019
• Actual Primary Completion Date: December 21, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03364751
• Other Study ID Numbers: P1-OHS-01-JP
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Philip Morris Products S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Philip Morris Products S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.

• PRS Account: Philip Morris Products S.A.
• Verification Date: January 2023