Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03837704
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : March 29, 2019
Sponsor:
Information provided by (Responsible Party):
Philip Morris Products S.A.

Tracking Information
First Submitted Date  ICMJE January 21, 2019
First Posted Date  ICMJE February 12, 2019
Last Update Posted Date March 29, 2019
Actual Study Start Date  ICMJE October 3, 2018
Estimated Primary Completion Date September 2, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
AAA annual growth rate over time [ Time Frame: At 6-month intervals from baseline to 5 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03837704 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Period of time from diagnosis of the AAA until open surgical AAA treatment or AAA endovascular repair or AAA rupture [ Time Frame: From diagnosis of AAA to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: At 6-month intervals from baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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) [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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 [ Time Frame: From baseline to 5 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking.
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Smoking
  • Abdominal Aortic Aneurysm
  • IQOS Use
Intervention  ICMJE
  • Other: IQOS
    AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.
  • Other: Cigarette
    AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.
  • Other: Smoking Cessation
    AAA patients who have completely quit smoking will continue to remain abstinent from smoking cigarettes or using any tobacco or nicotine-containing product(s)
Study Arms  ICMJE
  • Active Comparator: IQOS Arm
    Patients diagnosed with AAA, switching from cigarette smoking to IQOS use
    Intervention: Other: IQOS
  • Active Comparator: CC Arm
    Patients diagnosed with AAA, continuing to smoke cigarettes
    Intervention: Other: Cigarette
  • Active Comparator: Smoking Cessation Arm
    Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s)
    Intervention: Other: Smoking Cessation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2019)
114
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2025
Estimated Primary Completion Date September 2, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christelle Haziza, PhD 058 242 11 11 christelle.haziza@pmi.com
Contact: Cam Tuan Tran, MD
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03837704
Other Study ID Numbers  ICMJE P1-AAA-02-JP
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Philip Morris Products S.A.
Study Sponsor  ICMJE Philip Morris Products S.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Christelle Haziza, PhD Philip Morris Products SA
PRS Account Philip Morris Products S.A.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP