A Cross-sectional, Multi-regional Study to Demonstrate Reduction in Exposure to Key Toxicants, Oxidative Stress, and Inflammation Following at Least 2 Years of Tobacco Heating System (THS) Use Compared to Cigarette Smoking
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 974
- 试验地点
- 37
- 主要终点
- Carboxyhemoglobin (COHb) in blood
研究概览
简要总结
This is a cross-sectional 3-group study with subjects enrolled and matched by region (Asia, Europe), age, sex, and average daily product consumption over the last 2 years as self-reported. The study will be conducted as a multi-center and multi-regional study.
详细描述
The primary purpose of this study was to demonstrate the beneficial effects of switching from cigarette smoking to THS use for at least two years, compared to continued cigarette smoking, in real-life conditions. This was assessed by examining both inflammation and oxidative stress status as proxies for long-term harm in healthy subjects, using well-established and fit-for-purpose measures of WBC and 8-epi-PGF2α, respectively, as indicators of these pathways.
Additionally, the study anticipated observing differences in lipid metabolism (HDL-C), endothelial dysfunction (sICAM-1), platelet activation (11-DTX-B2), arterial stiffness (AIx), and lung function (FEV1 %pred post-BD).
The study also aimed to demonstrate additional benefits on other mechanistic pathways related to inflammation and oxidative stress through the use of additional biomarkers of potential harm (BoPH). Furthermore, it sought to assess the association with functional benefits that are expected to respond to the extent of exposure to harmful and potentially harmful constituents (HPHCs).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is able to understand the information provided in the main ICF and has signed the main ICF.
- •Subject is 30-60 years old.
- •Subject is healthy based on ECG, spirometry, vital signs, physical examination, medical history and Investigator's assessment.
- •Cigarette smokers:
- •Has smoked ≥ 10 cigarettes/day on average (no brand restriction) over the past 2 years prior to screening.
- •Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 10 years.
- •Has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past 2 years prior to screening.
- •Smoking status will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (≥ 10 ppm (1)).
- •Has used ≥ 10 HeatSticks/day on average over the past 2 years prior to screening.
- •Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to switching to THS.
- •Has smoked < 30 cigarettes/month and used other tobacco products or e-cigarettes < daily over the past 2 years prior to screening.
- •Product use will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (< 10 ppm).
- •Former cigarette smokers:
- •Has not smoked cigarettes or used any tobacco or nicotine-containing products on a daily basis over the past 2 years prior to screening.
- •Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to stopping smoking.
- •Smoking status will be verified by urinary cotinine test (< 100 ng/mL) and CO breath test (< 10 ppm).
排除标准
- •As per the judgment of the Investigator, the subject cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason). The Investigator should specifically evaluate the subject's eligibility considering COVID-19 risk factors and local situation.
- •The subject is legally incompetent or physically/mentally incapable of giving consent (e.g., emergency situation, under guardianship, in a social or sanitary establishment, prisoner or involuntarily incarcerated).
- •The subject has/had clinically relevant diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease) or conditions that in the opinion of the investigator would jeopardize the safety of the subject or affect the validity of the study results.
- •The subject has abnormal findings on physical examination, ECG, vital signs, spirometry or in the medical history, deemed clinically significant by investigators.
- •The subject has/had within 30 days prior to screening a body temperature >37.5°C or an acute illness (e.g., upper-respiratory-tract infection, viral infection, etc.…) or the subject is confirmed or suspected active COVID-19 infection (based on the signs and symptoms observed at the time of assessment) at screening.
- •The subject has used any prescribed or over-the-counter systemic medication with an impact on WBC or 8-epi-PGF2α within 5 half-lives of the medication prior to enrollment in the study (please refer to Appendix B).
- •Subject has high blood pressure (hypertension), defined as > 139 mmHg systolic and/or > 89 mmHg diastolic or is currently treated with medication controlling high blood pressure.
- •The subject has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator (BD) spirometry.
- •The subject has (FEV1/FVC) < 0.75 (pre-BD) and reversibility in FEV1 (that is both > 12% and > 200 mL from pre- to post-BD values).
- •The subject has a history of allergic reactions to salbutamol.
- •The subject has a body mass index (BMI) < 18.5 or ≥ 30 kg/m
- •The subject has positive alcohol and/or drug screening test results.
- •The subject has donated or received whole blood or blood products within 3 months prior to V
- •The subject has been previously screened for this study.
- •The subject is a current or former employee of the tobacco or e-cigarettes industry or of their first-degree relatives (parent, sibling, and child).
- •The subject is an employee of the investigational site or any other parties involved in the study or of their first-degree relatives (parent, sibling, and child).
- •The subject has participated in a clinical study within 3 months prior to V
- •For women only: the subject is pregnant (does have a positive pregnancy test) or breast-feeding.
结局指标
主要结局
Carboxyhemoglobin (COHb) in blood
时间窗: Measured when subject visits study site on day 1.
Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin.
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine
时间窗: Measured when subject visits study site on day 1.
Concentrations of total NNAL measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).
White Blood Cell total count (WBC) in blood
时间窗: Measured when subject visits study site on day 1.
Total count in blood (GI/L). Mean values are provided.
8-epi-Prostaglandin-F2α (8-epi-PGF2α) in urine
时间窗: Measured when subject visits study site on day 1.
Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).
次要结局
- soluble Intercellular Adhesion Molecule-1 (sICAM-1)(Measured when subject visits study site on day 1.)
- Forced Expiratory Volume in 1 second (FEV1) %predicted, post-bronchodilator (post-BD)(Measured when subject visits study site on day 1.)
- High-Density Lipoprotein Cholesterol (HDL-C)(Measured when subject visits study site on day 1.)
- 11-dehydrothromboxane B2 (11-DTX-B2)(Measured when subject visits study site on day 1.)
- Augmentation Index (AIx)(Measured when subject visits study site on day 1.)