A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers

NCT01553084 | Completed Phase 4 Results DMC

• 2 other identifiers: 1R01HL109031-012011-0756
• Study Type: interventional
• Target: 1,086
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Smoking Cessation; Smoking; Nicotine Dependence

Keywords

Smoking Cessation; Smoking; Nicotine

Outcome Measures

Primary Outcomes (1)

• Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks

  Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of \<10 ppm..

  Assessed 26 weeks after the target quit day.

Secondary Outcomes (3)

• Number of Days to Relapse

  Assessed from the target quit day through 26 weeks.

• Number of Participants With Initial Cessation in the First 7 Days Post-quit

  Assessed for the first seven days after the target quit date.

• The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT).

  Assessed at Baseline and Year 3

Study Arms (3)

Effectiveness of Nicotine patch only

EXPERIMENTAL

Drug: Nicotine Patch

Effectiveness of Combination NRT

EXPERIMENTAL

Drug: Nicotine lozenge; Drug: Nicotine Patch

Effectiveness of Varenicline [Chantix]

EXPERIMENTAL

Drug: Varenicline

Interventions

Varenicline 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.

Effectiveness of Varenicline [Chantix]

Nicotine lozenge 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.

Effectiveness of Combination NRT

Nicotine Patch 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; Effectiveness of Nicotine patch only

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

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

Madison, Wisconsin, 53711, United States

Location

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

Milwaukee, Wisconsin, 53233, United States

Location

Related Publications (7)

• 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.

  PMID: 26813210 RESULT

• 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.

  PMID: 39868569 DERIVED

• 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.

  PMID: 37142273 DERIVED

• 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.

  PMID: 35474254 DERIVED

• 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.

  PMID: 32800078 DERIVED

• 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.

  PMID: 31422759 DERIVED

• 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.

  PMID: 31056710 DERIVED

Related Links

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

MeSH Terms

Conditions

Smoking Cessation; Smoking; Tobacco Use Disorder

Interventions

Varenicline; Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Therapeutics

Results Point of Contact

• Title: Stevens S. Smith, Ph.D.
• Organization: Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health

sss@ctri.wisc.edu

6082627563

Study Officials

• Michael C Fiore, MD, MPH

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• James H Stein, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2011
• First Posted: March 13, 2012
• Study Start: May 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: August 1, 2017
• Last Updated: September 2, 2020
• Results First Posted: April 2, 2019

Record last verified: 2020-08

Locations

US (2)