UMIN-CTR Clinical Trial

Public 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.

Acronym

Comparison AAA growth in adult smoking patients who either switch to IQOS, continue smoking, or had stopped smoking.

Scientific 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.

Scientific Title:Acronym

Comparison AAA growth in adult smoking patients who either switch to IQOS, continue smoking, or had stopped smoking.

Region

Japan

Condition

Abdominal Aortic Aneurysm

Classification by specialty

Vascular surgery

Cardiovascular surgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the reduction in the AAA annual growth rate in patients who switch from smoking cigarettes (CC) to using IQOS, as compared to patients who continue to smoke CC (IQOS arm versus cigarette arm), also as compared to patients who had stopped smoking (IQOS arm versus SC arm), and to evaluate the reduction in the AAA annual growth rate in patients who continue to smoke CC as compared to patients who had stopped smoking (CC arm versus SC arm).

Basic objectives2

Others

Basic objectives -Others

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.

Trial characteristics_1

Others

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

(Endpoints for evaluation concerning Narrative objective1 )
･ Measurement of the maximum minor-axis AAA diameter in mm
･ AAA annual growth rate

Key secondary outcomes

To describe or evaluate the following outcomes in patients who switch from smoking CC to using IQOS, as compared to patients who continue smoking CC and patients who had stopped smoking. (Following 1-5):
1 Date of diagnosis/ decision to perform open surgical AAA treatment or AAA endovascular repair/ Date of AAA rupture
2 Number of patients with open surgical AAA treatment or AAA endovascular repair annually / Number of patients with AAA rupture annually
3 Number of patients with an increase in maximum minor-axis AAA diameter of more than 5 mm within 6 months/Number of patients with an overall maximum minor-axis AAA diameter >55mm in male patients and >50mm in female patients
4 The progression of AAA: See endpoints of secondary objectives and endpoints No 1 to No. 3.
5 Annual incidence of Ischemic Heart Disease(IHD), IHD progression or IHD related events/ of Chronic Obstructive Pulmonary Disease(COPD), COPD progression or a COPD related events/ of hypertension, progression of hypertension, progression of hypertension or a hypertension related events/ of Peripheral Arterial Disease(PAD), PAD progression or PAD related events/ of other smoking-related diseases and their related events.

6. Safety profiles

To describe about following outcomes in AAA patients who switch from smoking CC to using IQOS, patients who continue to smoke CC, and patients who had stopped smoking. (Following 7,8):
7. Nicotine exposure over time: Nicotine equivalents (NEQ)
8. Cardiovascular CREs/ BoExp to selected HPHCs

9. To describe the ankle-brachial index over time in AAA patients who switch from smoking CC to using IQOS, patients who continue to smoke CC, and patients who had stopped smoking.

10. To evaluate the transcriptomic, proteomic and lipidomic profiles in patients switching from CC to IQOS as compared to those continuing to smoke CC and patients who had stopped smoking.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

No treatment

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

3

Purpose of intervention

Prevention

Type of intervention

Other

Interventions/Control_1

IQOS arm: AAA patients randomized to the IQOS arm will be instructed to use exclusively IQOS ad libitum over the entire study period (no flavor restrictions).

Interventions/Control_2

Cigarette arm: AAA patients randomized to the cigarette arm will be instructed to continue smoking their cigarettes ad libitum over the entire study period (no brand restrictions).

Interventions/Control_3

Adults who had stopped smoking (as a non-randomized control arm): Patients who had completely quitted smoking within 2 months after their AAA diagnosis and are allocated to the SC arm, are instructed to refrain entirely from the use of any tobacco or nicotine-containing tobacco product (except nicotine replacement therapy [NRTs]) during the Investigational Period.

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

50

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1.Patient is aged >=50years
2.Patient is Japanese
3.Patient diagnosed with AAA(infrarenal,fusiform type)with a current aortic maximum minor-axis diameter of 30 to <=49mm(in male patient)and 30 to <=44mm(in female patient)
a)Diagnosis of AAA within the past 30months with at least two computerized tomography assessments since diagnosis. The two CT scans must show a time difference of at least 6months in between measurements
b)The maximum minor-axis AAA diameter to be used for assessment of eligibility is the maximum minor-axis AAA diameter available at the time of enrollment
4.Patient has smoked on average at least 10 commercially available CC per day for at least 5years prior to AAA diagnosis,based on self-reporting
5.Patient is ready to comply with the study protocol
Specific to patients screened for enrollment and randomization to the CC or IQOSarm: Seventy-six(76)female or male Japanese adult smokers with diagnosed AAA meeting the following additional main inclusion criteria will be enrolled and randomized in the CC and IQOSarm of the study:
6.Patient has smoked on average at least 10 commercially available CC per day for the last 12months,based on self-reporting. Intermittent attempts to quit smoking not exceeding 2months or short-term interruption of smoking up to 10days within the last 12months will be allowed. Smoking status will be verified based on a urinary cotinine test
7.Not intending to quit smoking within the next 6months after having been advised to quit smoking
Specific to patients screened for enrollment into the SCarm:
Thirty-eight female or male Japanese adult patients with diagnosed AAA meeting the following additional main inclusion criteria will be enrolled in the SCarm of the study:
8.Patient had completely quitted smoking and stopped the use of any other tobacco or nicotine-containing products within 2months after AAA diagnosis,and is still abstinent at Screening and at Baseline. Smoking status will be verified based on a urinary cotinine test

Key exclusion criteria

1. Patient is legally incompetent, physically or mentally incapable of giving consent.
2. Patient with acute severe cardiovascular events or respiratory diseases, within the last 3 months.
3. Patient with currently active cancer or history of cancer within the last 5 years.
4. Patient is ineligible as judged by the Investigator to participate in the study for any reason.
5. Patient with dissecting aneurysm(s) of the aorta.
6. Patient with infrarenal pseudo-AAA (false AAA).
7. Patient with a diagnosis of COPD Stage 3 and 4 in the medical history.
8. Patient with a recent (within 1 year) or current history of alcohol or other substance abuse based on self-reporting.
9. Female patient who is pregnant or breast-feeding.
10. 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.
11. Patient is a current or former employee of the tobacco industry or their first-degree relatives (parent and child).
12. Patient is an employee of the investigational site or any other parties involved in the study or their first-degree relatives (parent and child).
13. Patient has been previously screened or enrolled in this study).
14. Patient was enrolled in any clinical study within 3 months prior to V1.

Target sample size

114

Name of lead principal investigator

1st name
Middle name
Last name	Takeshi Baba

Organization

Jikei University Hospital

Division name

Division of vascular surgery

Zip code

Address

3-19-18, Nishishinbashi, Minato-ku, Tokyo, 105-8471, JAPAN

TEL

+81-3-3433-1111

Email

takeshi-baba@live.jp

Name of contact person

1st name
Middle name
Last name	Ryoko Ohara

Organization

CMIC Co., Ltd.

Division name

Project Management Division

Zip code

Address

Hamamatsucho Building 1-1-1 Shibaura,Minato-ku,Tokyo 105-0023 Japan

TEL

+81-70-6486-2991

Homepage URL

Email

ryoko-ohara.yp@cmic.co.jp

Institute

Philip Morris Products S.A.

Institute

Department

Personal name

Organization

Philip Morris Products S.A.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Switzerland

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

新百合ヶ丘総合病院 （神奈川県）/ ＡＯＩ国際病院（神奈川県）/ 埼玉県立循環器・呼吸器病センター（埼玉県）/ 厚木市立病院（神奈川県）/ 湘南鎌倉総合病院 （神奈川県）/ Shin Yurigaoka Hospital (Kanagawa Prefecture)/ AOI University Hospital (Kanagawa Prefecture) / Saitama Cardiovascular and Respiratory Center (Saitama Prefecture)/ Atsugi City Hospital (Kanagawa Prefecture)/ Shonan Kamakura General Hospital (Kanagawa Prefecture)

Date of disclosure of the study information

2019

Year

01

Month

11

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2018

Year

06

Month

25

Day

Date of IRB

Anticipated trial start date

2018

Year

10

Month

03

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2019

Year

01

Month

11

Day

Last modified on

2019

Year

01

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040452