Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking.
Primary Purpose
Smoking, Abdominal Aortic Aneurysm, IQOS Use
Status
Completed
Phase
Not Applicable
Locations
Japan
Study Type
Interventional
Intervention
IQOS
Cigarette
Smoking Cessation
Sponsored by
About this trial
This is an interventional basic science trial for Smoking
Eligibility Criteria
General Inclusion Criteria:
- Patient diagnosed with AAA (infrarenal, fusiform type) with a current aortic maximum minor-axis diameter of 30 to ≤ 49 mm (in male patient) and 30 to ≤ 44 mm (in female patient).
- Patient has smoked on average at least 10 commercially available CC per day (no brand restrictions) for at least 5 years prior to AAA diagnosis, based on self-reporting
- Patient is ready to comply with the study protocol (e.g., to use their assigned product/regimen during the course of the study)
Inclusion criteria specific to patients screened for enrollment and randomization to the CC or IQOS arm:
- Patient has smoked on average at least 10 commercially available CC per day (no brand restriction) for the last 12 months, based on self-reporting. Intermittent attempts to quit smoking not exceeding 2 months or short-term interruption of smoking up to 10 days within the last 12 months will be allowed. Smoking status will be verified based on a urinary cotinine test (i.e., cotinine ≥ 200 ng/mL).
- Not intending to quit smoking within the next 6 months.
Inclusion Criteria specific to patients screened for enrollment into the SC arm:
- Patient had completely quit smoking and stopped the use of any other tobacco or nicotine-containing products within 2 months after AAA diagnosis, and is still abstinent at Screening and at Baseline. Smoking status will be verified based on a urinary cotinine test (i.e., cotinine < 100 ng/mL).
Exclusion Criteria:
- Patient is legally incompetent, physically or mentally incapable of giving consent.
- Patient is a current or former employee of the tobacco industry or their first-degree relatives (parent and child); patient is an employee of the investigational site or any other parties involved in the study or their first-degree relatives (parent and child).
- Patient has been previously screened or enrolled in this study or was enrolled in any clinical study within 3 months prior to the Screening Visit.
- Female patient who is pregnant or breast-feeding.
- Patient is ineligible as judged by the Investigator to participate in the study for any reason.
- Patient with acute severe cardiovascular events or respiratory diseases, within the last 3 months; with currently active cancer or history of cancer within the last 5 years; with dissecting aneurysm(s) of the aorta; with infrarenal pseudo-AAA (false AAA); with a diagnosis of COPD Stage 3 and 4 in the medical history; with a recent (within 1 year) or current history of alcohol or other substance abuse based on self-reporting.
- Patient with a diagnosis of concomitant genetic diseases such as but not limited to Marfan syndrome, Loeys-Dietz syndrome, Vascular Ehlers-Danlos syndrome, Turner syndrome, Polycystic kidney disease, Noonan syndrome, Alagile syndrome, Arterial tortuosity syndrome and Cutis laxa.
Sites / Locations
- Atsugi City Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
IQOS Arm
CC Arm
Smoking Cessation Arm
Arm Description
Patients diagnosed with AAA, switching from cigarette smoking to IQOS use
Patients diagnosed with AAA, continuing to smoke cigarettes
Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s)
Outcomes
Primary Outcome Measures
AAA annual growth rate over time
AAA annual growth rate will be measured in AAA patients who switch from smoking cigarettes to using IQOS, and AAA patients who continue to smoke CC, as compared to AAA patients who had stopped smoking. Maximum minor-axis AAA diameter in mm will be measured. Annual growth rate will be calculated by annualizing the slope of the linear regression over the available diameter measurements.
Secondary Outcome Measures
Period of time from diagnosis of the AAA until open surgical AAA treatment or AAA endovascular repair or AAA rupture
The time from diagnosis of the AAA until open surgical AAA treatment or AAA endovascular repair or AAA rupture will be measured in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue smoking CC and AAA patients who had stopped smoking.
Incidence of open surgical AAA treatment or AAA endovascular repair and AAA rupture
The incidence of open surgical AAA treatment or AAA endovascular repair and AAA rupture will be measured in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue to smoke CC and AAA patients who had stopped smoking. Incidence rate will be calculated annually.
Incidence of AAA growth above 5 mm within 6 months
Incidence of AAA growth above 5 mm within 6 months will be measured in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue smoking CC and AAA patients who had stopped smoking. Incidence rate will be calculated annually by counting the number of patients with an increase in maximum minor-axis AAA diameter of more than 5 mm within 6 months.
AAA patients with an overall maximum minor-axis AAA diameter of >55mm in male patients and >50mm in female patients
The number of AAA patients with an overall maximum minor-axis AAA diameter >55mm in male AAA patients and >50mm in female AAA patients will be counted in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue smoking CC and AAA patients who had stopped smoking.
Incidence of ischemic heart disease (IHD) in AAA patients
Number of AAA patients with a diagnosis of IHD, IHD progression (by number of new myocardial infarction, stroke or death) or IHD related event annually.
Incidence of chronic obstructive pulmonary disease (COPD) in AAA patients
Number of AAA patients with a diagnosis of COPD, COPD progression (by disease stage) or a COPD related event annually.
Incidence of hypertension in AAA patients
Number of AAA patients with a diagnosis of hypertension, progression of their hypertension (by disease stage), or a hypertension related event annually.
Incidence of peripheral arterial disease (PAD) in AAA patients
Number of AAA patients with a diagnosis of PAD, PAD progression (by disease stage) or PAD related event annually.
Incidence rate of other smoking-related diseases, and their related events, in AAA patients
Number of AAA patients with adverse events related to the diagnosis of other co-morbidities, events related to the other co-morbidities.
Urinary nicotine equivalents (NEQ)
To measure nicotine exposure over time in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC, and AAA patients who had stopped smoking.
Systolic blood pressure
This cardiovascular clinical risk endpoint (systolic blood pressure) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Diastolic blood pressure
This cardiovascular clinical risk endpoint (diastolic blood pressure) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Body weight
This cardiovascular clinical risk endpoint (body weight) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Waist circumference
This cardiovascular clinical risk endpoint (waist circumference) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
High sensitive C-reactive protein (hs-CRP)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Low density lipoprotein (LDL)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
High density lipoprotein (HDL)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Total Cholesterol (TC)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Triglyceride (TG)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Fasting blood glucose
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Hemoglobin A1c (HbA1c)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
White blood cell (WBC) and platelet counts
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
D-dimer
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Fibrinogen
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Total Antioxidant Capacity (TAC)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
11-dehydro-thromboxane B2 (11-DTX-B2)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
8-Epi Prostaglandin F2 Alpha (8-epi-PGF2α)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Metalloproteinase 2 (MMP- 2)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, patients who continue to smoke CC and patients who had stopped smoking.
Metalloproteinase 9 (MMP-9)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, patients who continue to smoke CC and patients who had stopped smoking.
Soluble inter-cellular adhesion molecule-1 (sICAM-1)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Apolipoprotein A1 (Apo A1)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Apolipoprotein B (Apo B)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Homocysteine (Hcy)
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)
This biomarker of exposure to a tobacco smoke constituent will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Total N-nitrosonornicotine (Total NNN)
This biomarker of exposure to a tobacco smoke constituent will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
2-cyanoethylmercapturic acid (CEMA)
This biomarker of exposure to a tobacco smoke constituent will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Ankle-brachial index (ABI)
The ABI will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC, and AAA patients who had stopped smoking.
Transcriptomic profile assessment in blood samples
To evaluate differential changes in gene expressions, transcriptomics analyses will be performed on collected blood samples. Isolated RNAs will be applied to a gene chip that contains 54,000 transcripts. The gene chip will then be scanned using Affymetrix. The outcome measurements that will be reported are relative changes and relative fold changes in gene expressions in AAA patients who continue smoking cigarettes and those switching to IQOS.
Proteomic profile assessment in plasma derived from blood samples
To evaluate changes in selected protein concentrations, targeted proteomics analyses will be performed on plasma derived from collected blood samples. Proteins will be isolated from plasma and targeted proteomics analyses will be performed using liquid chromatography mass spectrometry (LC MS/MS) and antibody-based Luminex. The outcome measurements that will be reported are the concentrations of the selected proteins measured in AAA patients who continue smoking cigarettes and those switching to IQOS.
Lipidomic profile assessment in plasma derived from blood samples
To evaluate changes in selected ceramide concentrations, targeted lipidomics analyses will be performed on plasma derived from collected blood samples. Ceramides will be isolated from plasma and targeted lipidomics analyses will be performed using liquid chromatography mass spectrometry (LC MS/MS). The outcome measurements that will be reported are the concentrations of the selected ceramides measured in AAA patients who continue smoking cigarettes and those switching to IQOS.
Lipidomic profile assessment in urine
To evaluate changes in selected eicosanoid concentrations, targeted lipidomics analyses will be performed in urine. Eicosanoids will be isolated from urine and targeted lipidomics analyses will be performed using liquid chromatography mass spectrometry (LC MS/MS). The outcome measurements that will be reported are the concentrations of selected eicosanoids measured in AAA patients who continue smoking cigarettes and those switching to IQOS.
Full Information
NCT ID
NCT03837704
First Posted
January 21, 2019
Last Updated
September 6, 2023
Sponsor
Philip Morris Products S.A.
1. Study Identification
Unique Protocol Identification Number
NCT03837704
Brief Title
Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking.
Official Title
A Controlled, Open-label, 3-arm Parallel Group, Multi-center Study to Evaluate the Abdominal Aortic Aneurysm (AAA) Growth Rate in Adult Smoking Patients Randomized to Either Cigarette Smoking or IQOS Use and to Compare With the AAA Growth Rate in Patients Who Had Stopped Smoking
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
October 3, 2018 (Actual)
Primary Completion Date
April 8, 2023 (Actual)
Study Completion Date
August 28, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Philip Morris Products S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the reduction of the Abdominal Aortic Aneurysm (AAA) annual growth rate in patients who switch from smoking cigarettes to using IQOS as compared to patients who continue to smoke cigarettes. The study also aims to provide context to the scale of reduction in the growth rate, by comparing the AAA annual growth rates for continuing to smoke and switching to IQOS with the AAA annual growth rate in smokers who had stopped smoking. The study will further evaluate the effects of switching to IQOS on co-morbidities observed in AAA patients that are related to smoking as well as to assess the effects on relevant clinical risk endpoints linked to smoking related diseases.
Detailed Description
This is a controlled, open-label, 3-arm parallel group, multi-center study in patients diagnosed with Abdominal Aortic Aneurysm (AAA) to evaluate the AAA annual growth rate in adult smokers randomized to either continue smoking combustible cigarettes (CC) or to switch to IQOS and in adults who had stopped smoking, as a non-randomized control arm.
This is a descriptive study, designed to gain an understanding of how changes in smoking behaviors impact AAA growth rate and disease progression. Therefore, there are no formal statistical hypotheses to be tested.
Smoking patients with AAA who did not quit smoking after their AAA diagnosis, and who are not intending to quit within the next 6 months will be screened for enrollment and randomization in the CC and IQOS arms if all other eligibility criteria are met.
Smoking patients with AAA who had completely stopped smoking and using of any other tobacco or nicotine-containing products within 2 months of their AAA diagnosis, and are still abstinent at the time of the Screening Visit and of the Baseline Visit will be screened to be enrolled in the smoking cessation (SC) arm without randomization.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoking, Abdominal Aortic Aneurysm, IQOS Use
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IQOS Arm
Arm Type
Active Comparator
Arm Description
Patients diagnosed with AAA, switching from cigarette smoking to IQOS use
Arm Title
CC Arm
Arm Type
Active Comparator
Arm Description
Patients diagnosed with AAA, continuing to smoke cigarettes
Arm Title
Smoking Cessation Arm
Arm Type
Active Comparator
Arm Description
Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s)
Intervention Type
Other
Intervention Name(s)
IQOS
Intervention Description
AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.
Intervention Type
Other
Intervention Name(s)
Cigarette
Intervention Description
AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.
Intervention Type
Other
Intervention Name(s)
Smoking Cessation
Intervention Description
AAA patients who have completely quit smoking will continue to remain abstinent from smoking cigarettes or using any tobacco or nicotine-containing product(s)
Primary Outcome Measure Information:
Title
AAA annual growth rate over time
Description
AAA annual growth rate will be measured in AAA patients who switch from smoking cigarettes to using IQOS, and AAA patients who continue to smoke CC, as compared to AAA patients who had stopped smoking. Maximum minor-axis AAA diameter in mm will be measured. Annual growth rate will be calculated by annualizing the slope of the linear regression over the available diameter measurements.
Time Frame
At 6-month intervals from baseline to 5 years
Secondary Outcome Measure Information:
Title
Period of time from diagnosis of the AAA until open surgical AAA treatment or AAA endovascular repair or AAA rupture
Description
The time from diagnosis of the AAA until open surgical AAA treatment or AAA endovascular repair or AAA rupture will be measured in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue smoking CC and AAA patients who had stopped smoking.
Time Frame
From diagnosis of AAA to 5 years
Title
Incidence of open surgical AAA treatment or AAA endovascular repair and AAA rupture
Description
The incidence of open surgical AAA treatment or AAA endovascular repair and AAA rupture will be measured in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue to smoke CC and AAA patients who had stopped smoking. Incidence rate will be calculated annually.
Time Frame
From baseline to 5 years
Title
Incidence of AAA growth above 5 mm within 6 months
Description
Incidence of AAA growth above 5 mm within 6 months will be measured in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue smoking CC and AAA patients who had stopped smoking. Incidence rate will be calculated annually by counting the number of patients with an increase in maximum minor-axis AAA diameter of more than 5 mm within 6 months.
Time Frame
At 6-month intervals from baseline to 5 years
Title
AAA patients with an overall maximum minor-axis AAA diameter of >55mm in male patients and >50mm in female patients
Description
The number of AAA patients with an overall maximum minor-axis AAA diameter >55mm in male AAA patients and >50mm in female AAA patients will be counted in AAA patients who switch from smoking CC to using IQOS, as compared to AAA patients who continue smoking CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Incidence of ischemic heart disease (IHD) in AAA patients
Description
Number of AAA patients with a diagnosis of IHD, IHD progression (by number of new myocardial infarction, stroke or death) or IHD related event annually.
Time Frame
From baseline to 5 years
Title
Incidence of chronic obstructive pulmonary disease (COPD) in AAA patients
Description
Number of AAA patients with a diagnosis of COPD, COPD progression (by disease stage) or a COPD related event annually.
Time Frame
From baseline to 5 years
Title
Incidence of hypertension in AAA patients
Description
Number of AAA patients with a diagnosis of hypertension, progression of their hypertension (by disease stage), or a hypertension related event annually.
Time Frame
From baseline to 5 years
Title
Incidence of peripheral arterial disease (PAD) in AAA patients
Description
Number of AAA patients with a diagnosis of PAD, PAD progression (by disease stage) or PAD related event annually.
Time Frame
From baseline to 5 years
Title
Incidence rate of other smoking-related diseases, and their related events, in AAA patients
Description
Number of AAA patients with adverse events related to the diagnosis of other co-morbidities, events related to the other co-morbidities.
Time Frame
From baseline to 5 years
Title
Urinary nicotine equivalents (NEQ)
Description
To measure nicotine exposure over time in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC, and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Systolic blood pressure
Description
This cardiovascular clinical risk endpoint (systolic blood pressure) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Diastolic blood pressure
Description
This cardiovascular clinical risk endpoint (diastolic blood pressure) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Body weight
Description
This cardiovascular clinical risk endpoint (body weight) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Waist circumference
Description
This cardiovascular clinical risk endpoint (waist circumference) will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
High sensitive C-reactive protein (hs-CRP)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Low density lipoprotein (LDL)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
High density lipoprotein (HDL)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Total Cholesterol (TC)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Triglyceride (TG)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Fasting blood glucose
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Hemoglobin A1c (HbA1c)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
White blood cell (WBC) and platelet counts
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
D-dimer
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Fibrinogen
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Total Antioxidant Capacity (TAC)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
11-dehydro-thromboxane B2 (11-DTX-B2)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
8-Epi Prostaglandin F2 Alpha (8-epi-PGF2α)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Metalloproteinase 2 (MMP- 2)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, patients who continue to smoke CC and patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Metalloproteinase 9 (MMP-9)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, patients who continue to smoke CC and patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Soluble inter-cellular adhesion molecule-1 (sICAM-1)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Apolipoprotein A1 (Apo A1)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Apolipoprotein B (Apo B)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Homocysteine (Hcy)
Description
This cardiovascular clinical risk endpoint will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)
Description
This biomarker of exposure to a tobacco smoke constituent will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Total N-nitrosonornicotine (Total NNN)
Description
This biomarker of exposure to a tobacco smoke constituent will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
2-cyanoethylmercapturic acid (CEMA)
Description
This biomarker of exposure to a tobacco smoke constituent will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Ankle-brachial index (ABI)
Description
The ABI will be measured in AAA patients who switch from smoking CC to using IQOS, AAA patients who continue to smoke CC, and AAA patients who had stopped smoking.
Time Frame
From baseline to 5 years
Title
Transcriptomic profile assessment in blood samples
Description
To evaluate differential changes in gene expressions, transcriptomics analyses will be performed on collected blood samples. Isolated RNAs will be applied to a gene chip that contains 54,000 transcripts. The gene chip will then be scanned using Affymetrix. The outcome measurements that will be reported are relative changes and relative fold changes in gene expressions in AAA patients who continue smoking cigarettes and those switching to IQOS.
Time Frame
From baseline to 5 years
Title
Proteomic profile assessment in plasma derived from blood samples
Description
To evaluate changes in selected protein concentrations, targeted proteomics analyses will be performed on plasma derived from collected blood samples. Proteins will be isolated from plasma and targeted proteomics analyses will be performed using liquid chromatography mass spectrometry (LC MS/MS) and antibody-based Luminex. The outcome measurements that will be reported are the concentrations of the selected proteins measured in AAA patients who continue smoking cigarettes and those switching to IQOS.
Time Frame
From baseline to 5 years
Title
Lipidomic profile assessment in plasma derived from blood samples
Description
To evaluate changes in selected ceramide concentrations, targeted lipidomics analyses will be performed on plasma derived from collected blood samples. Ceramides will be isolated from plasma and targeted lipidomics analyses will be performed using liquid chromatography mass spectrometry (LC MS/MS). The outcome measurements that will be reported are the concentrations of the selected ceramides measured in AAA patients who continue smoking cigarettes and those switching to IQOS.
Time Frame
From baseline to 5 years
Title
Lipidomic profile assessment in urine
Description
To evaluate changes in selected eicosanoid concentrations, targeted lipidomics analyses will be performed in urine. Eicosanoids will be isolated from urine and targeted lipidomics analyses will be performed using liquid chromatography mass spectrometry (LC MS/MS). The outcome measurements that will be reported are the concentrations of selected eicosanoids measured in AAA patients who continue smoking cigarettes and those switching to IQOS.
Time Frame
From baseline to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
General Inclusion Criteria:
Patient diagnosed with AAA (infrarenal, fusiform type) with a current aortic maximum minor-axis diameter of 30 to ≤ 49 mm (in male patient) and 30 to ≤ 44 mm (in female patient).
Patient has smoked on average at least 10 commercially available CC per day (no brand restrictions) for at least 5 years prior to AAA diagnosis, based on self-reporting
Patient is ready to comply with the study protocol (e.g., to use their assigned product/regimen during the course of the study)
Inclusion criteria specific to patients screened for enrollment and randomization to the CC or IQOS arm:
Patient has smoked on average at least 10 commercially available CC per day (no brand restriction) for the last 12 months, based on self-reporting. Intermittent attempts to quit smoking not exceeding 2 months or short-term interruption of smoking up to 10 days within the last 12 months will be allowed. Smoking status will be verified based on a urinary cotinine test (i.e., cotinine ≥ 200 ng/mL).
Not intending to quit smoking within the next 6 months.
Inclusion Criteria specific to patients screened for enrollment into the SC arm:
Patient had completely quit smoking and stopped the use of any other tobacco or nicotine-containing products within 2 months after AAA diagnosis, and is still abstinent at Screening and at Baseline. Smoking status will be verified based on a urinary cotinine test (i.e., cotinine < 100 ng/mL).
Exclusion Criteria:
Patient is legally incompetent, physically or mentally incapable of giving consent.
Patient is a current or former employee of the tobacco industry or their first-degree relatives (parent and child); patient is an employee of the investigational site or any other parties involved in the study or their first-degree relatives (parent and child).
Patient has been previously screened or enrolled in this study or was enrolled in any clinical study within 3 months prior to the Screening Visit.
Female patient who is pregnant or breast-feeding.
Patient is ineligible as judged by the Investigator to participate in the study for any reason.
Patient with acute severe cardiovascular events or respiratory diseases, within the last 3 months; with currently active cancer or history of cancer within the last 5 years; with dissecting aneurysm(s) of the aorta; with infrarenal pseudo-AAA (false AAA); with a diagnosis of COPD Stage 3 and 4 in the medical history; with a recent (within 1 year) or current history of alcohol or other substance abuse based on self-reporting.
Patient with a diagnosis of concomitant genetic diseases such as but not limited to Marfan syndrome, Loeys-Dietz syndrome, Vascular Ehlers-Danlos syndrome, Turner syndrome, Polycystic kidney disease, Noonan syndrome, Alagile syndrome, Arterial tortuosity syndrome and Cutis laxa.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christelle Haziza, PhD
Organizational Affiliation
Philip Morris Products SA
Official's Role
Study Chair
Facility Information:
Facility Name
Atsugi City Hospital
City
Atsugi
State/Province
Kanagawa Prefecture
ZIP/Postal Code
243-8588
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking.
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