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

Effects of Switching From Cigarettes to Tobacco Heating System on Coronary Atherosclerosis Progression in Patients With Stable Coronary Artery Disease

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Nicotine Dependence; Coronary Atherosclerosis
• Intervention / Treatment: Behavioral: heated tobacco - lifestyle intervention

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).

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cezary Kepka, ND PhD; Phone Number: +48223434150; Email: ckepka@ikard.pl
• Study Contact Backup: Name: Mariusz Kruk, MD PhD; Phone Number: +48223434342; Email: mkruk@ikard.pl

Study Locations

• Poland
  • Warsaw, Poland, 04-628
    • National Institute of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults aged >18 years and <75 years
2. 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
3. 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
4. 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)
5. 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
6. Stable treatment for coronary atherosclerosis according to the guidelines
7. Have understood the study and have signed informed consent

Exclusion Criteria:

1. Any acute cardiovascular event (i.e. ACS, MI, Stroke, TIA, Limb ischemia), unstable angina or revascularization within 30 days prior to screening
2. Planned coronary intervention (PCI, CABG) at screening
3. Previous CABG
4. Preexisting heart failure with reduced ejection fraction (EF <50%)
5. Severe uncontrolled hypertension (at the discretion of investigator)
6. Diabetes
7. Subjects with documented genetic familial hypercholesterolemia
8. Subjects have known serious infection or chronic inflammatory systemic disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis)
9. Subjects have a known non-cardiovascular disease that is associated with poor prognosis (e.g. metastatic cancer)
10. Patient with currently active cancer or history of cancer within the last 5 years
11. Subjects have hypersensitivity or any other warnings listed in the local labeling for THS
12. Subjects have hypersensitivity to imaging iodine contrast agents
13. GFR<45 ml/min/1,73 m2
14. Subjects who could not participate for any reason other than medical (e.g., psychological and/or social reason) per Investigator's judgment
15. Subjects have any other clinical condition that would jeopardize the subject's safety while participating in this study, per Investigator's judgment
16. Female subject is pregnant or breast-feeding, or planning to become pregnant during the study
17. 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)
18. 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)
19. Subjects are current or former employee of the tobacco industry or their first-degree relatives (parent, child, spouse)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: combustion tobacco
Experimental: heated tobacco	Behavioral: heated tobacco - lifestyle intervention; Patients unable (unwilling) to stop smoking will be randomized to either combustion (C) or heated (H) tobacco groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in non calcified plaque volume between H and C groups ("intention to treat")	CCTA based evaluation	0-18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total plaque volume	CCTA based evaluation	0-18 months
Change in plaque volume components (low attenuation, fibrous-fatty, fibrous, non-calcified plaque, calcified plaque)	CCTA based evaluation	0-18 months
Change in non calcified plaque volume between H and C groups ("as treated")	CCTA based evaluation	0-18 months
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)	0-18 months
Change in oxidative stress	8-Epi prostaglandin F2 alpha (8 epi PGF2α) Myeloperoxidase (MPO)	0-18 months
Change in inflammation	High-sensitivity C-reactive protein (hs CRP) White blood cell (WBC) counts Homocysteine Interleukins (IL-6) Fibrinogen	0-18 months
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)	0-18 months
Change in endothelial dysfunction	P-selectin Metalloproteinase 9 (MMP-9)	0-18 months
Change in haemodynamic stress	N-terminal pro b-type natriuretic peptide (NT-proBNP)	0-18 months
Change in myocardial injury	high-sensitivity troponin T (hs-TnT)	0-18 months
Change in glycemia control	Fasting Blood Glucose, HbA1c	0-18 months
Change in physical activity	self reported, mobile device monitoring	0-18 months
Change in exposure to nicotine	4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol , Nicotine equivalents in spot urine , 2-cyanoethylmercapturic acid	0-18 months
SAFETY (ADVERSE OUTCOMES)	Independent DSMB will evaluate the outcomes	0-18 months
Change in self reported product use		0-18 months
Change in quality of life	EQ5D-5L	0-18 months
Cost/effectiveness analysis		0-18 months
Subgroup analysis (AGE/SEX/CO-MORBIDITIES)		1-18 months

Collaborators and Investigators

• Sponsor: Institute of Cardiology, Warsaw, Poland
• Collaborators: PMPSA

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 15, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Estimate): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Substance-Related Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Tobacco Use Disorder; Atherosclerosis
• Other Study ID Numbers: SWITCH01

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