A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers

NCT ID: NCT01553084

Last Updated: 2020-09-02

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

1086 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2017-08-31

Brief Summary

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The overall purpose of this research is two-fold. First, the two smoking cessation medication treatments with the strongest evidence of effectiveness have never been directly compared. This research will determine how these two treatments compare in effectiveness in a head-to-head trial, and which types of smokers benefit most from each. Second, much of the data on smoking and health come from studies from many years ago. Today's smokers differ from earlier smokers in many ways that could influence the impact of smoking on health (e.g., weight, sex, diet, socio-economic status); the proposed work will determine how smoking cessation affects cardiovascular and pulmonary health in today's smokers.

Detailed Description

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The proposed study will recruit and treat a large sample of contemporary smokers and former smokers at an age of increasing health risk, to achieve the following over-arching aims that are important to the NHLBI mission:

* Specific Aim 1: Produce important new data on how to treat smoking optimally by conducting an open label comparative effectiveness trial (CET) that for the first time directly contrasts the two smoking cessation pharmacotherapies with the strongest extant evidence of efficacy: combination NRT and varenicline.
* Specific Aim 2: Determine the impact of smoking cessation on biomarkers and health risk factors, especially those relevant to CVD, in today's smokers, which will elucidate the mechanisms via which cessation benefits health.
* Specific Aim 3: Identify which individuals are at greatest risk for exacerbation of biomarkers or risk factor status due to continued smoking, and who will benefit most from cessation. This will help identify individuals who are most in need of cessation intervention. While all smokers need to quit, this evidence could ultimately be used to help focus treatment and motivate smokers and clinicians to intervene more intensively with patients at greatest risk.

Two secondary aims are to use the results of Primary Aim 1 to develop a treatment assignment algorithm for the optimal treatment of today's smokers and to use the results from Primary Aim 2 to determine the relation of health biomarkers to clinically meaningful disease outcomes such as CVD events.

We will re-recruit as many smoking and non smoking participants from our past longitudinal cohort study("Wisconsin Smokers' Health study"; NCT01122238) in 2004. We will then recruit additional smokers to participate in the comparative effectiveness trial and join the longitudinal cohort..

All participants who enroll will complete questionnaires about their demographics, smoking history, withdrawal symptoms, affect, alcohol use, stressors, medication usage and diet. They will also complete a structured clinical interview to assess mental health. They will provide blood samples for testing of various markers of cardiovascular disease and risk as well as for genetics testing. They will all have carotid ultrasounds, pulmonary function tests, arterial tonometry assessments, and 12-lead ECGs. Participants in Madison will also have a treadmill stress test. Participants will wear a pedometer for 1 week and record the daily number of steps. Participants will provide permission for staff to review their medical charts to assess smoking-relevant diagnoses and treatment. These assessments will occur at baseline and again 3 years later. A smaller subset of these assessments will also be conducted 1 year after enrollment. Participants will also complete brief phone assessments at 6-month intervals up to the 3-year visit.

Interested and eligible smoking participants from the original cohort study and all newly recruited participants will enroll in a new smoking cessation intervention study. Participants in the cessation treatment study will be randomly assigned to receive the nicotine patch, nicotine patch + nicotine lozenge or varenicline. If the participant from the original cohort study is not eligible to use all study medications but is otherwise eligible for cessation treatment, s/he will be assigned to a non-randomized treatment arm and will receive nicotine patch (if appropriate). All cessation participants will receive 6 individual counseling sessions.

Conditions

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Smoking Cessation Smoking Nicotine Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Effectiveness of Nicotine patch only

Group Type EXPERIMENTAL

Nicotine Patch

Intervention Type DRUG

Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.

Effectiveness of Combination NRT

Group Type EXPERIMENTAL

Nicotine lozenge

Intervention Type DRUG

Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects.

Nicotine Patch

Intervention Type DRUG

Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.

Effectiveness of Varenicline [Chantix]

Group Type EXPERIMENTAL

Varenicline

Intervention Type DRUG

Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.

Interventions

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Varenicline

Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.

Intervention Type DRUG

Nicotine lozenge

Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects.

Intervention Type DRUG

Nicotine Patch

Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

a. To be eligible for the Comparative effectiveness trial, participants must:

* smoke 5 or more cigarettes per day,
* desire to quit smoking but not be currently engaged in cessation treatment,
* be medically eligible to use either combination NRT or varenicline,
* have reliable phone access,
* if female, must not be pregnant and must be willing to use an acceptable birth control method.

Exclusion Criteria

2. All smoking participants from new and original cohorts will be excluded from the cessation trial for the following reasons:

* end-stage renal disease with hemodialysis;
* prior suicide attempts within the last 5 years or current suicidal ideation;
* diagnosis of and/or treatment for schizophrenia;
* other psychotic disorders or bipolar disorder within the last 10 years;
* current PHQ-9 score indicative of moderately severe depression;
* severe untreated hypertension \>200/100 mmHg;
* currently taking Wellbutrin, Zyban or bupropion;
* hospitalized for a stroke, heart attack, congestive heart failure or diabetes within the last year;
* used pipe tobacco, cigars, snuff or chew more than twice in the past week.

It should be noted that if any incidental findings appear in any of the cardiology tests (e.g., ultrasound, tonometry, ECG, or exercise stress test; see forms in Supplemental Information section of application), the study cardiologist (Dr. Stein or his designee) will be assign the participant to the non-randomized treatment arm and they will be given the nicotine patch and the same counseling intervention as CET participants. They will not be included in the CET analyses. This will be done to properly address the cardiovascular risk warning from the FDA regarding varenicline (Chantix).
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael C Fiore, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

James H Stein, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health

Madison, Wisconsin, United States

Site Status

University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Baker TB, Piper ME, Stein JH, Smith SS, Bolt DM, Fraser DL, Fiore MC. Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial. JAMA. 2016 Jan 26;315(4):371-9. doi: 10.1001/jama.2015.19284.

Reference Type RESULT
PMID: 26813210 (View on PubMed)

Theodoulou A, Fanshawe TR, Leavens E, Theodoulou E, Wu AD, Heath L, Stewart C, Nollen N, Ahluwalia JS, Butler AR, Hajizadeh A, Thomas J, Lindson N, Hartmann-Boyce J. Differences in the effectiveness of individual-level smoking cessation interventions by socioeconomic status. Cochrane Database Syst Rev. 2025 Jan 27;1(1):CD015120. doi: 10.1002/14651858.CD015120.pub2.

Reference Type DERIVED
PMID: 39868569 (View on PubMed)

Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Reference Type DERIVED
PMID: 37142273 (View on PubMed)

Karim R, Xu W, Kono N, Sriprasert I, Li Y, Yan M, Stanczyk FZ, Shoupe D, Mack WJ, Hodis HN. Effect of menopausal hormone therapy on arterial wall echomorphology: Results from the Early versus Late Intervention Trial with Estradiol (ELITE). Maturitas. 2022 Aug;162:15-22. doi: 10.1016/j.maturitas.2022.02.007. Epub 2022 Mar 17.

Reference Type DERIVED
PMID: 35474254 (View on PubMed)

Kaye JT, Johnson AL, Baker TB, Piper ME, Cook JW. Searching for Personalized Medicine for Binge Drinking Smokers: Smoking Cessation Using Varenicline, Nicotine Patch, or Combination Nicotine Replacement Therapy. J Stud Alcohol Drugs. 2020 Jul;81(4):426-435. doi: 10.15288/jsad.2020.81.426.

Reference Type DERIVED
PMID: 32800078 (View on PubMed)

Mitchell C, Piper ME, Smith SS, Korcarz CE, Fiore MC, Baker TB, Stein JH. Changes in carotid artery structure with smoking cessation. Vasc Med. 2019 Dec;24(6):493-500. doi: 10.1177/1358863X19867762. Epub 2019 Aug 17.

Reference Type DERIVED
PMID: 31422759 (View on PubMed)

Schlam TR, Baker TB, Smith SS, Cook JW, Piper ME. Anxiety Sensitivity and Distress Tolerance in Smokers: Relations With Tobacco Dependence, Withdrawal, and Quitting Successdagger. Nicotine Tob Res. 2020 Jan 27;22(1):58-65. doi: 10.1093/ntr/ntz070.

Reference Type DERIVED
PMID: 31056710 (View on PubMed)

Related Links

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http://www.ctri.wisc.edu/

University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health

Other Identifiers

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1R01HL109031-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2011-0756

Identifier Type: OTHER

Identifier Source: secondary_id

1R01HL109031-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link

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