Trial Outcomes & Findings for Comparison of Abdominal Aortic Aneurysm Growth in Adult Smoking Patients Who Either Switch to IQOS, Continue Smoking, or Quit Smoking. (NCT NCT03837704)

Last Updated: 2025-08-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

48 participants

Primary outcome timeframe

At 6-month intervals from baseline to V8 (month 36)

Results posted on

2025-08-26

Participant Flow

Participant milestones

Participant milestones
Measure	IQOS Arm Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Completed V3 (Month 6) STARTED	16	16	16
Completed V3 (Month 6) COMPLETED	16	16	16
Completed V3 (Month 6) NOT COMPLETED	0	0	0
Completed V4 (Month 12) STARTED	16	16	16
Completed V4 (Month 12) COMPLETED	16	16	15
Completed V4 (Month 12) NOT COMPLETED	0	0	1
Completed V5 (Month 18) STARTED	16	16	15
Completed V5 (Month 18) COMPLETED	16	14	14
Completed V5 (Month 18) NOT COMPLETED	0	2	1
Completed V6 (Month 24) STARTED	16	14	14
Completed V6 (Month 24) COMPLETED	14	13	14
Completed V6 (Month 24) NOT COMPLETED	2	1	0
Completed V7 (Month 30) STARTED	14	13	14
Completed V7 (Month 30) COMPLETED	14	12	14
Completed V7 (Month 30) NOT COMPLETED	0	1	0
Completed V8 (Month 36) STARTED	14	12	14
Completed V8 (Month 36) COMPLETED	13	11	14
Completed V8 (Month 36) NOT COMPLETED	1	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IQOS Arm n=16 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)	Total n=48 Participants Total of all reporting groups
Age, Continuous	71.0 years STANDARD_DEVIATION 6.19 • n=5 Participants	70.4 years STANDARD_DEVIATION 7.73 • n=7 Participants	71.3 years STANDARD_DEVIATION 2.59 • n=5 Participants	70.9 years STANDARD_DEVIATION 5.79 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants	48 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	16 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants	48 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Nationality Japanese	16 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants	48 Participants n=4 Participants
Nationality Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: At 6-month intervals from baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=15 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
AAA Annual Growth Rate Over Time	1.80 (mm/year) Interval 0.94 to 2.66	1.87 (mm/year) Interval 1.33 to 2.4	1.27 (mm/year) Interval 0.84 to 1.7

SECONDARY outcome

Timeframe: From time of AAA diagnosis (prior to study participation) until V8 (month 36), a time frame of up to 7 years

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time Baseline -36 months	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time Baseline -24 months	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	87.5 percentage Interval 58.6 to 96.7
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time Baseline -12 months	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	87.5 percentage Interval 58.6 to 96.7
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time V2 (Baseline)	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	87.5 percentage Interval 58.6 to 96.7
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time V4 (Month 12)	83.9 percentage Interval 49.4 to 95.7	80.0 percentage Interval 40.9 to 94.6	87.5 percentage Interval 58.6 to 96.7
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time V6 (Month 24)	83.9 percentage Interval 49.4 to 95.7	80.0 percentage Interval 40.9 to 94.6	87.5 percentage Interval 58.6 to 96.7
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Endovascular Repair Over Time V8 (Month 36)	83.9 percentage Interval 49.4 to 95.7	80.0 percentage Interval 40.9 to 94.6	87.5 percentage Interval 58.6 to 96.7

SECONDARY outcome

Timeframe: From time of AAA diagnosis (prior to study participation) until V8 (month 36), a time frame of up to 7 years

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time Baseline -36 months	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time Baseline -24 months	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time Baseline -12 months	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time V2 (Baseline)	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time V4 (Month 12)	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time V6 (Month 24)	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0
Percentage of Subjects Without Open Surgical AAA Treatment or AAA Rupture Over Time V8 (Month 36)	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0	100.0 percentage Interval 100.0 to 100.0

SECONDARY outcome

Timeframe: From baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Incidence of Open Surgical AAA Treatment or AAA Endovascular Repair and AAA Rupture Number of patients with open surgical AAA treatment or endovascular repair annually	0.05 events per person-year	0.05 events per person-year	0.05 events per person-year
Incidence of Open Surgical AAA Treatment or AAA Endovascular Repair and AAA Rupture Number of patients with AAA rupture annually	0.00 events per person-year	0.00 events per person-year	0.00 events per person-year

SECONDARY outcome

Timeframe: At 6-month intervals from baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Incidence of AAA Growth Above 5 mm Within 6 Months	0 events per person-year Interval 0.0 to 0.2	0 events per person-year Interval 0.0 to 0.2	0 events per person-year Interval 0.0 to 0.2

SECONDARY outcome

Timeframe: From baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population

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).

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
AAA Patients With an Overall Maximum Minor-axis AAA Diameter of >55mm in Male Patients and >50mm in Female Patients	0 participants Interval 0.0 to 0.2	0 participants Interval 0.0 to 0.2	0 participants Interval 0.0 to 0.2

SECONDARY outcome

Timeframe: From V1 (screening) to V8 (month 36)

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=16 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Systolic Blood Pressure V5 (Month 18)	133.9 mmHg Interval 125.9 to 141.9	130.6 mmHg Interval 124.6 to 136.7	126.9 mmHg Interval 120.0 to 133.9
Systolic Blood Pressure V6 (Month 24)	136.6 mmHg Interval 127.3 to 146.0	129.7 mmHg Interval 120.7 to 138.7	128.1 mmHg Interval 121.1 to 135.2
Systolic Blood Pressure V1 (Screening)	134.8 mmHg Interval 126.6 to 143.0	128.0 mmHg Interval 119.1 to 136.9	124.0 mmHg Interval 117.1 to 130.9
Systolic Blood Pressure V2 (Baseline)	132.5 mmHg Interval 122.9 to 142.1	128.9 mmHg Interval 120.1 to 137.8	135.9 mmHg Interval 129.7 to 142.2
Systolic Blood Pressure V3 (Month 6)	138.8 mmHg Interval 129.0 to 148.6	131.1 mmHg Interval 123.8 to 138.5	130.3 mmHg Interval 121.5 to 139.0
Systolic Blood Pressure V4 (Month 12)	132.7 mmHg Interval 125.5 to 140.0	135.0 mmHg Interval 128.5 to 141.5	129.3 mmHg Interval 121.2 to 137.5
Systolic Blood Pressure V7 (Month 30)	128.8 mmHg Interval 121.1 to 136.5	136.1 mmHg Interval 130.5 to 141.7	126.0 mmHg Interval 114.1 to 137.9
Systolic Blood Pressure V8 (Month 36)	131.7 mmHg Interval 124.6 to 138.8	131.6 mmHg Interval 126.2 to 137.1	125.3 mmHg Interval 116.5 to 134.0

SECONDARY outcome

Timeframe: From baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

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)).

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Urinary Nicotine Equivalents (NEQ) V2 (Baseline)	5.70 mg/g creat Interval 4.22 to 7.72	6.30 mg/g creat Interval 4.16 to 9.54	0 mg/g creat Interval 0.0 to 0.0
Urinary Nicotine Equivalents (NEQ) V3 (Month 6)	5.13 mg/g creat Interval 4.06 to 6.47	7.46 mg/g creat Interval 5.39 to 10.32	0 mg/g creat Interval 0.0 to 0.0
Urinary Nicotine Equivalents (NEQ) V4 (Month 12)	4.30 mg/g creat Interval 2.43 to 7.61	5.50 mg/g creat Interval 3.16 to 9.59	0 mg/g creat Interval 0.0 to 0.0
Urinary Nicotine Equivalents (NEQ) V5 (Month 18)	5.86 mg/g creat Interval 3.18 to 10.78	0.0 mg/g creat Interval 0.0 to 0.0	0 mg/g creat Interval 0.0 to 0.0
Urinary Nicotine Equivalents (NEQ) V6 (Month 24)	4.65 mg/g creat Interval 2.7 to 8.02	4.32 mg/g creat Interval 1.97 to 9.48	0 mg/g creat Interval 0.0 to 0.0
Urinary Nicotine Equivalents (NEQ) V7 (Month 30)	3.88 mg/g creat Interval 2.22 to 6.78	4.24 mg/g creat Interval 1.98 to 9.07	0 mg/g creat Interval 0.0 to 0.0
Urinary Nicotine Equivalents (NEQ) V8 (Month 36)	0 mg/g creat Interval 0.0 to 0.0	4.20 mg/g creat Interval 1.46 to 12.07	0 mg/g creat Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From V1 (screening) to V8 (month 36)

Population: Full Analysis Set (FAS) population.

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=16 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Diastolic Blood Pressure V1 (Screening)	75.4 mmHg Interval 69.6 to 81.1	76.6 mmHg Interval 71.0 to 82.2	72.9 mmHg Interval 67.5 to 78.4
Diastolic Blood Pressure V2 (Baseline)	76.6 mmHg Interval 70.5 to 82.6	76.6 mmHg Interval 71.5 to 81.6	77.3 mmHg Interval 73.0 to 81.5
Diastolic Blood Pressure V3 (Month 6)	79.7 mmHg Interval 75.0 to 84.3	77.3 mmHg Interval 73.4 to 81.2	73.9 mmHg Interval 68.1 to 79.6
Diastolic Blood Pressure V4 (Month 12)	76.3 mmHg Interval 70.5 to 82.2	77.3 mmHg Interval 70.8 to 83.7	74.1 mmHg Interval 68.0 to 80.1
Diastolic Blood Pressure V5 (Month 18)	74.8 mmHg Interval 69.2 to 80.4	78.3 mmHg Interval 72.4 to 84.2	71.5 mmHg Interval 67.4 to 75.6
Diastolic Blood Pressure V6 (Month 24)	79.0 mmHg Interval 74.3 to 83.7	78.5 mmHg Interval 71.6 to 85.5	72.7 mmHg Interval 68.3 to 77.1
Diastolic Blood Pressure V7 (Month 30)	76.3 mmHg Interval 72.5 to 80.1	79.8 mmHg Interval 73.9 to 85.6	69.2 mmHg Interval 62.9 to 75.5
Diastolic Blood Pressure V8 (Month 36)	73.8 mmHg Interval 68.0 to 79.5	77.8 mmHg Interval 70.7 to 84.9	67.0 mmHg Interval 61.5 to 72.5

SECONDARY outcome

Timeframe: From V1 (screening) to V8 (month 36)

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=16 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Body Weight V1 (Screening)	68.44 kg Interval 61.68 to 75.19	66.63 kg Interval 60.48 to 72.78	67.91 kg Interval 62.34 to 73.48
Body Weight V2 (Baseline)	68.13 kg Interval 61.51 to 74.75	66.61 kg Interval 60.47 to 72.74	67.93 kg Interval 62.39 to 73.47
Body Weight V3 (Month 6)	67.79 kg Interval 61.04 to 74.54	65.88 kg Interval 60.0 to 71.76	67.98 kg Interval 62.56 to 73.4
Body Weight V4 (Month 12)	68.47 kg Interval 61.53 to 75.42	66.51 kg Interval 60.42 to 72.59	67.27 kg Interval 61.38 to 73.16
Body Weight V5 (Month 18)	69.41 kg Interval 62.02 to 76.81	67.60 kg Interval 61.22 to 73.98	66.70 kg Interval 60.47 to 72.93
Body Weight V6 (Month 24)	68.51 kg Interval 62.41 to 74.61	67.82 kg Interval 60.19 to 75.45	67.14 kg Interval 61.06 to 73.21
Body Weight V7 (Month 30)	67.61 kg Interval 61.7 to 73.53	69.08 kg Interval 61.79 to 76.38	66.03 kg Interval 59.84 to 72.22
Body Weight V8 (Month 36)	68.74 kg Interval 62.36 to 75.12	69.71 kg Interval 61.56 to 77.86	66.34 kg Interval 59.61 to 73.08

SECONDARY outcome

Timeframe: From V1 (screening) to V8 (month 36)

Population: Full Analysis Set (FAS) population

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=16 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Waist Circumference V1 (Screening)	90.51 cm Interval 85.59 to 95.44	90.30 cm Interval 85.11 to 95.49	91.40 cm Interval 86.57 to 96.23
Waist Circumference V2 (Baseline)	89.88 cm Interval 84.61 to 95.14	91.01 cm Interval 85.1 to 96.91	93.33 cm Interval 88.8 to 97.85
Waist Circumference V3 (Month 6)	89.95 cm Interval 84.9 to 95.0	89.91 cm Interval 84.06 to 95.75	91.16 cm Interval 86.5 to 95.81
Waist Circumference V4 (Month 12)	89.75 cm Interval 84.17 to 95.34	89.46 cm Interval 84.39 to 94.54	91.78 cm Interval 86.74 to 96.82
Waist Circumference V5 (Month 18)	91.73 cm Interval 86.6 to 96.85	90.71 cm Interval 84.99 to 96.42	91.82 cm Interval 86.81 to 96.83
Waist Circumference V6 (Month 24)	89.14 cm Interval 81.91 to 96.36	91.55 cm Interval 84.13 to 98.97	91.54 cm Interval 86.91 to 96.16
Waist Circumference V7 (Month 30)	89.04 cm Interval 84.25 to 93.82	93.33 cm Interval 86.51 to 100.16	91.43 cm Interval 86.59 to 96.27
Waist Circumference V8 (Month 36)	91.78 cm Interval 87.65 to 95.9	92.30 cm Interval 85.63 to 98.97	91.36 cm Interval 85.93 to 96.79

SECONDARY outcome

Timeframe: From baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

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.

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V2 (Baseline)	124.09 pg/mg creat Interval 81.11 to 189.85	87.34 pg/mg creat Interval 55.98 to 136.27	0 pg/mg creat Interval 0.0 to 0.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V3 (Month 6)	39.83 pg/mg creat Interval 17.74 to 89.41	108.70 pg/mg creat Interval 73.72 to 160.27	0 pg/mg creat Interval 0.0 to 0.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V4 (Month 12)	27.12 pg/mg creat Interval 10.69 to 68.83	81.24 pg/mg creat Interval 52.33 to 126.12	0 pg/mg creat Interval 0.0 to 0.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V5 (Month 18)	32.81 pg/mg creat Interval 12.77 to 84.33	61.85 pg/mg creat Interval 33.78 to 113.27	0 pg/mg creat Interval 0.0 to 0.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V6 (Month 24)	33.02 pg/mg creat Interval 12.7 to 85.89	57.78 pg/mg creat Interval 31.17 to 107.11	0 pg/mg creat Interval 0.0 to 0.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V7 (Month 30)	27.54 pg/mg creat Interval 10.09 to 75.21	61.78 pg/mg creat Interval 31.22 to 122.26	0 pg/mg creat Interval 0.0 to 0.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) V8 (Month 36)	35.24 pg/mg creat Interval 12.12 to 102.43	42.36 pg/mg creat Interval 15.3 to 117.29	0 pg/mg creat Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Total N-nitrosonornicotine (Total NNN) V2 (Baseline)	3.26 pg/mg creatinine Interval 1.78 to 5.97	2.09 pg/mg creatinine Interval 1.0 to 4.38	0 pg/mg creatinine Interval 0.0 to 0.0
Total N-nitrosonornicotine (Total NNN) V3 (Month 6)	1.39 pg/mg creatinine Interval 0.73 to 2.68	2.86 pg/mg creatinine Interval 1.61 to 5.09	0 pg/mg creatinine Interval 0.0 to 0.0
Total N-nitrosonornicotine (Total NNN) V4 (Month 12)	0.98 pg/mg creatinine Interval 0.42 to 2.3	2.12 pg/mg creatinine Interval 1.0 to 4.49	0 pg/mg creatinine Interval 0.0 to 0.0
Total N-nitrosonornicotine (Total NNN) V5 (Month 18)	1.28 pg/mg creatinine Interval 0.5 to 3.28	1.47 pg/mg creatinine Interval 0.54 to 4.0	0 pg/mg creatinine Interval 0.0 to 0.0
Total N-nitrosonornicotine (Total NNN) V6 (Month 24)	1.34 pg/mg creatinine Interval 0.51 to 3.52	1.55 pg/mg creatinine Interval 0.51 to 4.68	0 pg/mg creatinine Interval 0.0 to 0.0
Total N-nitrosonornicotine (Total NNN) V7 (Month 30)	1.20 pg/mg creatinine Interval 0.44 to 3.24	1.31 pg/mg creatinine Interval 0.5 to 3.48	0 pg/mg creatinine Interval 0.0 to 0.0
Total N-nitrosonornicotine (Total NNN) V8 (Month 36)	1.10 pg/mg creatinine Interval 0.37 to 3.27	1.27 pg/mg creatinine Interval 0.37 to 4.41	0 pg/mg creatinine Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From baseline to V8 (month 36)

Population: Full Analysis Set (FAS) population. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Outcome measures

Outcome measures
Measure	IQOS Arm n=15 Participants Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 Participants Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 Participants Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
2-cyanoethylmercapturic Acid (2-CyEMA) V2 (Baseline)	95.38 ng/mg creat Interval 71.93 to 126.48	98.95 ng/mg creat Interval 64.68 to 151.37	2.36 ng/mg creat Interval 1.36 to 4.1
2-cyanoethylmercapturic Acid (2-CyEMA) V3 (Month 6)	20.21 ng/mg creat Interval 8.29 to 49.27	111.31 ng/mg creat Interval 74.3 to 166.76	1.67 ng/mg creat Interval 0.99 to 2.81
2-cyanoethylmercapturic Acid (2-CyEMA) V4 (Month 12)	13.29 ng/mg creat Interval 4.61 to 38.34	82.46 ng/mg creat Interval 51.19 to 132.83	2.30 ng/mg creat Interval 1.1 to 4.8
2-cyanoethylmercapturic Acid (2-CyEMA) V5 (Month 18)	12.53 ng/mg creat Interval 4.58 to 34.27	56.77 ng/mg creat Interval 26.94 to 119.63	1.70 ng/mg creat Interval 0.82 to 3.51
2-cyanoethylmercapturic Acid (2-CyEMA) V6 (Month 24)	13.88 ng/mg creat Interval 4.22 to 45.68	48.40 ng/mg creat Interval 18.83 to 124.44	1.77 ng/mg creat Interval 0.77 to 4.06
2-cyanoethylmercapturic Acid (2-CyEMA) V7 (Month 30)	8.25 ng/mg creat Interval 2.72 to 24.99	52.08 ng/mg creat Interval 20.21 to 134.23	1.51 ng/mg creat Interval 0.76 to 3.01
2-cyanoethylmercapturic Acid (2-CyEMA) V8 (Month 36)	12.32 ng/mg creat Interval 3.31 to 45.91	46.19 ng/mg creat Interval 13.07 to 163.23	1.86 ng/mg creat Interval 0.92 to 3.77

Adverse Events

IQOS Arm

Serious events: 3 serious events

Other events: 14 other events

Deaths: 1 deaths

CC Arm

Serious events: 5 serious events

Other events: 13 other events

Deaths: 1 deaths

Smoking Cessation Arm

Serious events: 7 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Head Clinical Development & Operations

Philip Morris Products S.A.

Phone: +41 58 242 11 11

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee We confirm we have the contractual provisions in place which specify that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements. The Intellectual Property rights and research results from the present study belong to the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	IQOS Arm n=16 participants at risk Patients diagnosed with AAA, switching from cigarette smoking to IQOS use IQOS: AAA patients will switch from cigarette smoking to ad libitum IQOS use, with no flavor variant restrictions.	CC Arm n=16 participants at risk Patients diagnosed with AAA, continuing to smoke cigarettes Cigarette: AAA patients will continue to smoke their cigarettes ad libitum, with no brand restrictions.	Smoking Cessation Arm n=16 participants at risk Patients diagnosed with AAA, who have completely stopped smoking and are not using any other tobacco or nicotine-containing product(s) 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)
Cardiac disorders Atrial fibrillation	12.5% 2/16 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
General disorders Death	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Cardiac disorders Angina unstable	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Cardiac disorders Acute myocardial infarction	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Cardiac disorders Angina pectoris	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Cardiac disorders Cardiac failure	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Cardiac disorders Myocardial ischaemia	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Eye disorders Cataract	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Gastrointestinal disorders Ileus	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Gastrointestinal disorders Inguinal hernia	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Gastrointestinal disorders Large intestine polyp	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	18.8% 3/16 • Number of events 3 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Infections and infestations Appendicitis	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Infections and infestations Gastroenteritis	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Infections and infestations Pneumonia	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Injury, poisoning and procedural complications Femoral neck fracture	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Injury, poisoning and procedural complications Patella fracture	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Inflammatory pseudotumour	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Nervous system disorders Cerebral haemorrhage	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Nervous system disorders Tarsal tunnel syndrome	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	0.00% 0/16 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.	6.2% 1/16 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 37 months.