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Effects of Switching From Cigarettes to Tobacco Heating System on Coronary Atherosclerosis Progression (SWITCH)

Primary Purpose

Coronary Artery Disease, Coronary Atherosclerosis, Nicotine Dependence

Status
Not yet recruiting
Phase
Not Applicable
Locations
Poland
Study Type
Interventional
Intervention
heated tobacco - lifestyle intervention
Sponsored by
National Institute of Cardiology, Warsaw, Poland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Coronary Artery Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adults aged >18 years and <75 years Subjects with stable chronic coronary syndrome defined as the presence of at least one coronary artery stenosis >=20% due to coronary plaque visible on coronary computed tomography angiography (CCTA), in an artery with a reference diameter > 2.0mm History of smoking pack-years ≥10 (Pack-years will be calculated by taking the average number of cigarettes smoked per day divided by 20 and multiplied by the number of years smoked), based on self-reporting Current smokers with a minimum of self-reported current smoking pattern of >10 cigarettes/day during the last 6 months prior to screening, smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL) Patients that have been advised to quit smoking and informed of a smoking risk and cessation programs (per local SOC) and who are still not willing to set a quit date within the next 30 days at screening Stable treatment for coronary atherosclerosis according to the guidelines Have understood the study and have signed informed consent Exclusion Criteria: Any acute cardiovascular event (i.e. ACS, MI, Stroke, TIA, Limb ischemia), unstable angina or revascularization within 30 days prior to screening Planned coronary intervention (PCI, CABG) at screening Previous CABG Preexisting heart failure with reduced ejection fraction (EF <50%) Severe uncontrolled hypertension (at the discretion of investigator) Diabetes Subjects with documented genetic familial hypercholesterolemia Subjects have known serious infection or chronic inflammatory systemic disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis) Subjects have a known non-cardiovascular disease that is associated with poor prognosis (e.g. metastatic cancer) Patient with currently active cancer or history of cancer within the last 5 years Subjects have hypersensitivity or any other warnings listed in the local labeling for THS Subjects have hypersensitivity to imaging iodine contrast agents GFR<45 ml/min/1,73 m2 Subjects who could not participate for any reason other than medical (e.g., psychological and/or social reason) per Investigator's judgment Subjects have any other clinical condition that would jeopardize the subject's safety while participating in this study, per Investigator's judgment Female subject is pregnant or breast-feeding, or planning to become pregnant during the study Subjects have previously participated in this study, or in an interventional study (drug or medical device) within 30 days of screening (participation in observational studies/registries allowed) Subjects have a close affiliation with the investigational site: a close relative of the investigator, a person dependent on the investigational site (e.g. employee or student of the investigational site) Subjects are current or former employee of the tobacco industry or their first-degree relatives (parent, child, spouse)

Sites / Locations

  • National Institute of Cardiology

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

combustion tobacco

heated tobacco

Arm Description

Outcomes

Primary Outcome Measures

Change in non calcified plaque volume between H and C groups ("intention to treat")
CCTA based evaluation

Secondary Outcome Measures

Change in total plaque volume
CCTA based evaluation
Change in plaque volume components (low attenuation, fibrous-fatty, fibrous, non-calcified plaque, calcified plaque)
CCTA based evaluation
Change in non calcified plaque volume between H and C groups ("as treated")
CCTA based evaluation
Change in lipid metabolism
Total cholesterol (TC) Triglycerides (TG) Lipoproteins: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) Apolipoproteins: apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) Lipoprotein(a) Lp(a)
Change in oxidative stress
8-Epi prostaglandin F2 alpha (8 epi PGF2α) Myeloperoxidase (MPO)
Change in inflammation
High-sensitivity C-reactive protein (hs CRP) White blood cell (WBC) counts Homocysteine Interleukins (IL-6) Fibrinogen
Change in platelet activation
11-dehydro-thromboxane B2 (11 DTX B2) Plasminogen activator inhibitor-1 (PAI-1) Tissue plasminogen activator (t-PA) Platelet count Mean platelet volume (MPV)
Change in endothelial dysfunction
P-selectin Metalloproteinase 9 (MMP-9)
Change in haemodynamic stress
N-terminal pro b-type natriuretic peptide (NT-proBNP)
Change in myocardial injury
high-sensitivity troponin T (hs-TnT)
Change in glycemia control
Fasting Blood Glucose, HbA1c
Change in physical activity
self reported, mobile device monitoring
Change in exposure to nicotine
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol , Nicotine equivalents in spot urine , 2-cyanoethylmercapturic acid
SAFETY (ADVERSE OUTCOMES)
Independent DSMB will evaluate the outcomes
Change in self reported product use
Change in quality of life
EQ5D-5L
Cost/effectiveness analysis
Subgroup analysis (AGE/SEX/CO-MORBIDITIES)

Full Information

First Posted
October 12, 2022
Last Updated
December 27, 2022
Sponsor
National Institute of Cardiology, Warsaw, Poland
Collaborators
PMPSA
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1. Study Identification

Unique Protocol Identification Number
NCT05660798
Brief Title
Effects of Switching From Cigarettes to Tobacco Heating System on Coronary Atherosclerosis Progression
Acronym
SWITCH
Official Title
Effects of Switching From Cigarettes to Tobacco Heating System on Coronary Atherosclerosis Progression in Patients With Stable Coronary Artery Disease
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Cardiology, Warsaw, Poland
Collaborators
PMPSA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Objective: To evaluate the impact of heated versus combustion tobacco products on progression of atherosclerosis in patients with CAD unable(unwilling) to quit smoking. Rationale: Despite the efforts to curb smoking and full awareness of its deleterious health impact, smoking remains a significant contributor to morbidity and mortality. Some health impact of smoking may be improved by other forms of cigarettes than traditional combustion, especially for subjects unwilling or unable to stop smoking. As recently as 2020, one of heated tobacco products (HTP)(IQOS) was FDA Authorized as a 'Reduced Exposure' product. The available evidence to date allows to conclude that the IQOS system heats tobacco but does not burn it, which significantly reduces the production of harmful and potentially harmful chemicals. Scientific studies have shown that switching completely from conventional cigarettes to the IQOS system significantly reduced body's exposure to harmful or potentially harmful chemicals. There is also evidence indicating lower levels of inflammatory markers and improved vascular function associated with use of heated tobacco products. However, it is unknown whether the reduction in the exposure translates into potential reduction of harm within cardiovascular system, as compared to the traditional (combustion) cigarettes. The evidence is of crucial importance for patients with cardiovascular diseases, medical community, and national health authorities planning evidence based policies regarding HTP/cigarettes.
Detailed Description
Objective: To evaluate the impact of heated versus combustion tobacco products on progression of atherosclerosis in patients with CAD unable(unwilling) to quit smoking. Background Despite the efforts to curb smoking and full awareness of its deleterious health impact, smoking remains a significant contributor to morbidity and mortality. Some health impact of smoking may be improved by other forms of cigarettes than traditional combustion, especially for subjects unwilling or unable to stop smoking. As recently as 2020, one of heated tobacco products (HTP)(IQOS) was FDA Authorized as a 'Reduced Exposure' product. The available evidence to date allows to conclude that the IQOS system heats tobacco but does not burn it, which significantly reduces the production of harmful and potentially harmful chemicals. Scientific studies have shown that switching completely from conventional cigarettes to the IQOS system significantly reduced body's exposure to harmful or potentially harmful chemicals. There is also evidence indicating lower levels of inflammatory markers and improved vascular function associated with use of heated tobacco products. However, it is unknown whether the reduction in the exposure translates into potential reduction of harm within cardiovascular system, as compared to the traditional (combustion) cigarettes. The evidence is of crucial importance for patients with cardiovascular diseases, medical community, and national health authorities planning evidence based policies regarding HTP/cigarettes. Methods: Prospective, single-centre, open-label, randomised study including 180 stable patients with coronary artery disease (CAD) as diagnosed on CCTA, without indications for invasive treatment, unable(unwilling) to quit smoking, randomised 1:1 to either heated (group H) or combustion (group C) tobacco products and followed for 18 months. The follow-up is accomplished with CCTA scan. The study clinical visits are planned at 1, 3, 6, 12, and 18 months. The primary outcome is change in non calcified plaque volume at 18 months between H and C groups (intention to treat design).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Coronary Atherosclerosis, Nicotine Dependence

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
combustion tobacco
Arm Type
No Intervention
Arm Title
heated tobacco
Arm Type
Experimental
Intervention Type
Behavioral
Intervention Name(s)
heated tobacco - lifestyle intervention
Intervention Description
Patients unable (unwilling) to stop smoking will be randomized to either combustion (C) or heated (H) tobacco groups.
Primary Outcome Measure Information:
Title
Change in non calcified plaque volume between H and C groups ("intention to treat")
Description
CCTA based evaluation
Time Frame
0-18 months
Secondary Outcome Measure Information:
Title
Change in total plaque volume
Description
CCTA based evaluation
Time Frame
0-18 months
Title
Change in plaque volume components (low attenuation, fibrous-fatty, fibrous, non-calcified plaque, calcified plaque)
Description
CCTA based evaluation
Time Frame
0-18 months
Title
Change in non calcified plaque volume between H and C groups ("as treated")
Description
CCTA based evaluation
Time Frame
0-18 months
Title
Change in lipid metabolism
Description
Total cholesterol (TC) Triglycerides (TG) Lipoproteins: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) Apolipoproteins: apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) Lipoprotein(a) Lp(a)
Time Frame
0-18 months
Title
Change in oxidative stress
Description
8-Epi prostaglandin F2 alpha (8 epi PGF2α) Myeloperoxidase (MPO)
Time Frame
0-18 months
Title
Change in inflammation
Description
High-sensitivity C-reactive protein (hs CRP) White blood cell (WBC) counts Homocysteine Interleukins (IL-6) Fibrinogen
Time Frame
0-18 months
Title
Change in platelet activation
Description
11-dehydro-thromboxane B2 (11 DTX B2) Plasminogen activator inhibitor-1 (PAI-1) Tissue plasminogen activator (t-PA) Platelet count Mean platelet volume (MPV)
Time Frame
0-18 months
Title
Change in endothelial dysfunction
Description
P-selectin Metalloproteinase 9 (MMP-9)
Time Frame
0-18 months
Title
Change in haemodynamic stress
Description
N-terminal pro b-type natriuretic peptide (NT-proBNP)
Time Frame
0-18 months
Title
Change in myocardial injury
Description
high-sensitivity troponin T (hs-TnT)
Time Frame
0-18 months
Title
Change in glycemia control
Description
Fasting Blood Glucose, HbA1c
Time Frame
0-18 months
Title
Change in physical activity
Description
self reported, mobile device monitoring
Time Frame
0-18 months
Title
Change in exposure to nicotine
Description
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol , Nicotine equivalents in spot urine , 2-cyanoethylmercapturic acid
Time Frame
0-18 months
Title
SAFETY (ADVERSE OUTCOMES)
Description
Independent DSMB will evaluate the outcomes
Time Frame
0-18 months
Title
Change in self reported product use
Time Frame
0-18 months
Title
Change in quality of life
Description
EQ5D-5L
Time Frame
0-18 months
Title
Cost/effectiveness analysis
Time Frame
0-18 months
Title
Subgroup analysis (AGE/SEX/CO-MORBIDITIES)
Time Frame
1-18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults aged >18 years and <75 years Subjects with stable chronic coronary syndrome defined as the presence of at least one coronary artery stenosis >=20% due to coronary plaque visible on coronary computed tomography angiography (CCTA), in an artery with a reference diameter > 2.0mm History of smoking pack-years ≥10 (Pack-years will be calculated by taking the average number of cigarettes smoked per day divided by 20 and multiplied by the number of years smoked), based on self-reporting Current smokers with a minimum of self-reported current smoking pattern of >10 cigarettes/day during the last 6 months prior to screening, smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL) Patients that have been advised to quit smoking and informed of a smoking risk and cessation programs (per local SOC) and who are still not willing to set a quit date within the next 30 days at screening Stable treatment for coronary atherosclerosis according to the guidelines Have understood the study and have signed informed consent Exclusion Criteria: Any acute cardiovascular event (i.e. ACS, MI, Stroke, TIA, Limb ischemia), unstable angina or revascularization within 30 days prior to screening Planned coronary intervention (PCI, CABG) at screening Previous CABG Preexisting heart failure with reduced ejection fraction (EF <50%) Severe uncontrolled hypertension (at the discretion of investigator) Diabetes Subjects with documented genetic familial hypercholesterolemia Subjects have known serious infection or chronic inflammatory systemic disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis) Subjects have a known non-cardiovascular disease that is associated with poor prognosis (e.g. metastatic cancer) Patient with currently active cancer or history of cancer within the last 5 years Subjects have hypersensitivity or any other warnings listed in the local labeling for THS Subjects have hypersensitivity to imaging iodine contrast agents GFR<45 ml/min/1,73 m2 Subjects who could not participate for any reason other than medical (e.g., psychological and/or social reason) per Investigator's judgment Subjects have any other clinical condition that would jeopardize the subject's safety while participating in this study, per Investigator's judgment Female subject is pregnant or breast-feeding, or planning to become pregnant during the study Subjects have previously participated in this study, or in an interventional study (drug or medical device) within 30 days of screening (participation in observational studies/registries allowed) Subjects have a close affiliation with the investigational site: a close relative of the investigator, a person dependent on the investigational site (e.g. employee or student of the investigational site) Subjects are current or former employee of the tobacco industry or their first-degree relatives (parent, child, spouse)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cezary Kepka, ND PhD
Phone
+48223434150
Email
ckepka@ikard.pl
First Name & Middle Initial & Last Name or Official Title & Degree
Mariusz Kruk, MD PhD
Phone
+48223434342
Email
mkruk@ikard.pl
Facility Information:
Facility Name
National Institute of Cardiology
City
Warsaw
ZIP/Postal Code
04-628
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30879375
Citation
Biondi-Zoccai G, Sciarretta S, Bullen C, Nocella C, Violi F, Loffredo L, Pignatelli P, Perri L, Peruzzi M, Marullo AGM, De Falco E, Chimenti I, Cammisotto V, Valenti V, Coluzzi F, Cavarretta E, Carrizzo A, Prati F, Carnevale R, Frati G. Acute Effects of Heat-Not-Burn, Electronic Vaping, and Traditional Tobacco Combustion Cigarettes: The Sapienza University of Rome-Vascular Assessment of Proatherosclerotic Effects of Smoking ( SUR - VAPES ) 2 Randomized Trial. J Am Heart Assoc. 2019 Mar 19;8(6):e010455. doi: 10.1161/JAHA.118.010455.
Results Reference
background
PubMed Identifier
34083663
Citation
Ikonomidis I, Vlastos D, Kostelli G, Kourea K, Katogiannis K, Tsoumani M, Parissis J, Andreadou I, Alexopoulos D. Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function. Sci Rep. 2021 Jun 3;11(1):11808. doi: 10.1038/s41598-021-91245-9.
Results Reference
background

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Effects of Switching From Cigarettes to Tobacco Heating System on Coronary Atherosclerosis Progression

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