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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Philip Morris Products S.A.
- Enrollment
- 48
- Locations
- 26
- Primary Endpoint
- AAA Annual Growth Rate Over Time
Study Overview
Brief Summary
The purpose of this study was to evaluate the reduction of the Abdominal Aortic Aneurysm (AAA) annual growth rate in patients who switched from smoking cigarettes to using IQOS as compared to patients who continued to smoke cigarettes, and to patients who had quit smoking. The study also aimed 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 further evaluated 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 Biomarkers of Potential Harm (BoPH) linked to smoking related diseases.
Detailed Description
This was 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 was a descriptive study, designed to gain an understanding of how changes in smoking behaviors impact AAA growth rate and disease progression. Therefore, there were no formal statistical hypotheses to be tested.
Smoking patients with AAA who did not quit smoking after their AAA diagnosis, and who were not intending to quit within the next 6 months were screened for enrollment and randomization in the CC and IQOS arms if all other eligibility criteria were met.
Smoking patients with AAA who had completely stopped smoking and using any other tobacco or nicotine-containing products within 2 months of their AAA diagnosis, and were still abstinent at the time of the Screening Visit and of the Baseline Visit were screened to be enrolled in the smoking cessation (SC) arm without randomization.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 50 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 a daily basis (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 5 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 after having been advised to quit smoking.
- •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 6 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.
Outcomes
Primary Outcomes
AAA Annual Growth Rate Over Time
Time Frame: At 6-month intervals from baseline to V8 (month 36)
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 Outcomes
- Systolic Blood Pressure(From V1 (screening) to V8 (month 36))
- Urinary Nicotine Equivalents (NEQ)(From baseline to V8 (month 36))
- Diastolic Blood Pressure(From V1 (screening) to V8 (month 36))
- Body Weight(From V1 (screening) to V8 (month 36))
- Waist Circumference(From V1 (screening) to V8 (month 36))
- Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)(From baseline to V8 (month 36))
- Total N-nitrosonornicotine (Total NNN)(From baseline to V8 (month 36))
- 2-cyanoethylmercapturic Acid (2-CyEMA)(From baseline to V8 (month 36))
- Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time(From time of AAA diagnosis (prior to study participation) until V8 (month 36), a time frame of up to 7 years)
- Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time(From time of AAA diagnosis (prior to study participation) until V8 (month 36), a time frame of up to 7 years)
- Incidence of Open Surgical AAA Treatment or AAA Endovascular Repair and AAA Rupture(From baseline to V8 (month 36))
- Incidence of AAA Growth Above 5 mm Within 6 Months(At 6-month intervals from baseline to V8 (month 36))
- AAA Patients With an Overall Maximum Minor-axis AAA Diameter of >55mm in Male Patients and >50mm in Female Patients(From baseline to V8 (month 36))