Clinical trial NCT03837704: 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
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Abdominal Aortic Aneurysm
IQOS Use
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2019-02-12
Enrollment: 48
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: AAA annual growth rate over time
timeFrame: At 6-month intervals from baseline to 5 years
Secondary outcomes:
measure: Period of time from diagnosis of the AAA until open surgical AAA treatment or AAA endovascular repair or AAA rupture
timeFrame: From diagnosis of AAA to 5 years
measure: Incidence of open surgical AAA treatment or AAA endovascular repair and AAA rupture
timeFrame: From baseline to 5 years
measure: Incidence of AAA growth above 5 mm within 6 months
timeFrame: At 6-month intervals from baseline to 5 years
measure: AAA patients with an overall maximum minor-axis AAA diameter of >55mm in male patients and >50mm in female patients
timeFrame: From baseline to 5 years
measure: Incidence of ischemic heart disease (IHD) in AAA patients
timeFrame: From baseline to 5 years
measure: Incidence of chronic obstructive pulmonary disease (COPD) in AAA patients
timeFrame: From baseline to 5 years
measure: Incidence of hypertension in AAA patients
timeFrame: From baseline to 5 years
measure: Incidence of peripheral arterial disease (PAD) in AAA patients
timeFrame: From baseline to 5 years
measure: Incidence rate of other smoking-related diseases, and their related events, in AAA patients
timeFrame: From baseline to 5 years
measure: Urinary nicotine equivalents (NEQ)
timeFrame: From baseline to 5 years
measure: Systolic blood pressure
timeFrame: From baseline to 5 years
measure: Diastolic blood pressure
timeFrame: From baseline to 5 years
measure: Body weight
timeFrame: From baseline to 5 years
measure: Waist circumference
timeFrame: From baseline to 5 years
measure: High sensitive C-reactive protein (hs-CRP)
timeFrame: From baseline to 5 years
measure: Low density lipoprotein (LDL)
timeFrame: From baseline to 5 years
measure: High density lipoprotein (HDL)
timeFrame: From baseline to 5 years
measure: Total Cholesterol (TC)
timeFrame: From baseline to 5 years
measure: Triglyceride (TG)
timeFrame: From baseline to 5 years
measure: Fasting blood glucose
timeFrame: From baseline to 5 years
measure: Hemoglobin A1c (HbA1c)
timeFrame: From baseline to 5 years
measure: White blood cell (WBC) and platelet counts
timeFrame: From baseline to 5 years
measure: D-dimer
timeFrame: From baseline to 5 years
measure: Fibrinogen
timeFrame: From baseline to 5 years
measure: Total Antioxidant Capacity (TAC)
timeFrame: From baseline to 5 years
measure: 11-dehydro-thromboxane B2 (11-DTX-B2)
timeFrame: From baseline to 5 years
measure: 8-Epi Prostaglandin F2 Alpha (8-epi-PGF2α)
timeFrame: From baseline to 5 years
measure: Metalloproteinase 2 (MMP- 2)
timeFrame: From baseline to 5 years
measure: Metalloproteinase 9 (MMP-9)
timeFrame: From baseline to 5 years
measure: Soluble inter-cellular adhesion molecule-1 (sICAM-1)
timeFrame: From baseline to 5 years
measure: Apolipoprotein A1 (Apo A1)
timeFrame: From baseline to 5 years
measure: Apolipoprotein B (Apo B)
timeFrame: From baseline to 5 years
measure: Homocysteine (Hcy)
timeFrame: From baseline to 5 years
measure: Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)
timeFrame: From baseline to 5 years
measure: Total N-nitrosonornicotine (Total NNN)
timeFrame: From baseline to 5 years
measure: 2-cyanoethylmercapturic acid (CEMA)
timeFrame: From baseline to 5 years
measure: Ankle-brachial index (ABI)
timeFrame: From baseline to 5 years
measure: Transcriptomic profile assessment in blood samples
timeFrame: From baseline to 5 years
measure: Proteomic profile assessment in plasma derived from blood samples
timeFrame: From baseline to 5 years
measure: Lipidomic profile assessment in plasma derived from blood samples
timeFrame: From baseline to 5 years
measure: Lipidomic profile assessment in urine
timeFrame: From baseline to 5 years
Other outcomes:
Locations:
city: Atsugi
country: Japan
facility: Atsugi City Hospital
state: Kanagawa Prefecture
Study officials:
affiliation: Philip Morris Products SA
name: Christelle Haziza, PhD
role: STUDY_CHAIR
References: