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

Not Applicable

Completed

Conditions: Abdominal Aortic Aneurysm
IQOS Use
Smoking

Registration Number: NCT03837704

Lead Sponsor: Philip Morris Products S.A.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
AAA Annual Growth Rate Over Time	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 Outcome Measures

Name	Time	Method
Systolic Blood Pressure	From V1 (screening) to V8 (month 36)	This cardiovascular BoPH (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.
Urinary Nicotine Equivalents (NEQ)	From baseline to V8 (month 36)	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. (NEQ adjusted for creatinine (mg/g creat)).
Diastolic Blood Pressure	From V1 (screening) to V8 (month 36)	This cardiovascular BoPH (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	From V1 (screening) to V8 (month 36)	This cardiovascular BoPH (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	From V1 (screening) to V8 (month 36)	This cardiovascular BoPH (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.
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)	From baseline to V8 (month 36)	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)	From baseline to V8 (month 36)	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 (2-CyEMA)	From baseline to V8 (month 36)	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.
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	This outcome measured the percentage of subjects without surgery or endovascular repair over time 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.
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	This outcome measured the percentage of subjects without surgery or AAA rupture over time 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	From baseline to V8 (month 36)	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	At 6-month intervals from baseline to V8 (month 36)	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	From baseline to V8 (month 36)	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. (Note that the 95% CI is calculated by exact method (Clopper-Pearson) and refers to CI for a proportion).

Trial Locations

Locations (13): Chiba-Nishi General Hospital
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Matsudo, Chiba, Japan
Tokyo Bay Urayasu Ichikawa Medical Center
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Urayasu, Chiba, Japan
Fujita General Hospital
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Fujita, Fukushima, Japan
Kitakanto Cardiology Hospital
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Shizukawa, Gunma, Japan
Shonan Kamakura General Hospital
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Okamoto, Kamakura, Japan
AOI Universal Hospital
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Kawasaki, Kanagawa, Japan
Shin-Yurigaoka General Hospital
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Kawasaki, Kanagawa, Japan
Saitama Cardiovascular and Respiratory Center
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Itai, Kumagaya, Japan
Kishiwada Tokushukai Hospital
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Kishiwada, Osaka, Japan
Kasukabe Chuo General Hospital
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Kasukabe, Saitama, Japan
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Chiba-Nishi General Hospital
🇯🇵Matsudo, Chiba, Japan