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

Study Overview
=================
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.

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.

Conditions
-----------------
Periodontal Diseases, Chronic Periodontitis, Periodontal Pocket, Tooth Mobility, Gingival Diseases, Smoking, Cigarette

Intervention / Treatment
-----------------
* Other: IQOS
* Other: Cigarette


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Patient is aged ≥ 30 years old. Patient has smoked on average at least 10 commercially available cigarettes per day for at least 5 years Patient has generalized chronic periodontitis (i.e., more than 30% of diseased teeth with a PD ≥ 4 mm). Main Exclusion Criteria: Patient has self-reported history of diagnosed systemic diseases (e.g., stroke or acute cardiovascular event within the last 5 years, diabetes, active cancer). Patient received root planing therapy within the 6 months prior to Visit 1. Patient received surgical periodontal therapy within 3 years prior to Visit Patient was treated within the 3 months prior to Visit 1 with systemic antibiotics or was treated with topical antibiotics applied in the mouth. 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). Female patients who are pregnant, breast-feeding, or planning a pregnancy within the course of the study.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Oral Health, Smoking, Cigarette, Reduced risk product, Tobacco heating system, Modified risk tobacco product, Clinical attachment level, THS