Cessation Screening Project

NCT04188873 | Completed Phase 4 DMC FDA Drug

• 5 other identifiers: 2019-00542P01CA180945A534253SMPH/MEDICINE/MEDICINE*GProtocol Version 10/9/2023
• Study Type: interventional
• Target: 529
• Locations: 1 country
• Sites: 2

Brief Summary

This project will use the Multiphase Optimization Strategy (MOST) to guide the development of optimized treatment strategies for the two most effective smoking cessation medications (Combination Nicotine Replacement \[C-NRT\] and varenicline). The investigators will recruit daily smokers from primary care to participate in a fully crossed, 2x2x2x2 factorial experiment (N=608) that evaluates 4 different factors: 1) Medication Type (Varenicline vs. C-NRT), 2) Preparation Medication (4 Weeks vs. Standard), 3) Medication Duration (Extended \[24 weeks\] vs. Standard \[12 weeks\]); and 4) Counseling (Intensive vs. Minimal). Participants will complete assessments one week pre-quit and then assessments of smoking status, treatment use, side effects, potential treatment mechanisms (e.g., withdrawal, self-efficacy) during the first week post-target quit date (TQD) and at Weeks 2, 4, 12, 20, 26, and 52 post-target quit date. These data will be used to examine the main and interactive effects of these four factors on various outcomes, with biochemically confirmed 12-month abstinence serving as the primary outcome. These data will also be used to determine which factors and combinations of factors are most effective with regard to 12-month biochemically confirmed abstinence and cost, thereby identifying optimized varenicline and C-NRT treatments, with each developed to yield especially great benefit. These optimized treatments will then be tested in the Optimized Care Project. The investigators will also examine the relative effects of each medication on particular outcomes (e.g., 12-month abstinence).

Conditions

Nicotine Dependence

Outcome Measures

Primary Outcomes (1)

• Intent-to-treat biochemically verified 7-day point prevalence abstinence

  Participants will be asked to report on any smoking in the last seven days at a follow-up phone interview scheduled to occur 12-months post-target quit day (post-TQD). Those claiming complete abstinence (not even a puff from a cigarette) in the last seven days at this follow-up interview will be asked to provide a saliva sample for biochemical verification of self-reported abstinence via cotinine testing. Participants who report abstinence in the last 7 days at this visit but have a cotinine level \>10ng/mL or who do not have provide a cotinine result will be considered to be smoking.

  12 months post-target quit day (TQD)

Secondary Outcomes (1)

• Cost-effectiveness

  12 months post-target quit day (TQD)

Study Arms (16)

12-week Varenicline with Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 11 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Standard Duration Varenicline; Behavioral: Minimal Counseling

12-week Varenicline with 4-Week Preparation Varenicline and Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 12 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Preparation Varenicline and Standard Duration Varenicline; Behavioral: Minimal Counseling

24-week Varenicline with Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 23 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Extended Duration Varenicline; Behavioral: Minimal Counseling

24-week Varenicline with 4-Week Preparation Varenicline and Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 weeks prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 24 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Preparation Varenicline and Extended Duration Varenicline; Behavioral: Minimal Counseling

12-week Varenicline with Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 11 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Standard Duration Varenicline; Behavioral: Intensive Counseling

12-week Varenicline with 4-Week Preparation Varenicline and Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 11 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Preparation Varenicline and Standard Duration Varenicline; Behavioral: Intensive Counseling

24-week Varenicline with Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 23 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Extended Duration Varenicline; Behavioral: Intensive Counseling

24-week Varenicline with 4-Week Preparation Varenicline and Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 weeks prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 24 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Preparation Varenicline and Extended Duration Varenicline; Behavioral: Intensive Counseling

12-week C-NRT with Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 12 weeks of nicotine patches and nicotine mini-lozenges to use starting on their quit day. Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Standard Duration Combination NRT; Behavioral: Minimal Counseling

12-week C-NRT with 4-Week Preparation C-NRT and Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Then, starting on the TQD, participants will receive 12 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke \>10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive a brief 15-30 minute phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Preparation Combination NRT and Standard Duration Combination NRT; Behavioral: Minimal Counseling

24-week C-NRT with Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 24 weeks of nicotine patches and nicotine mini-lozenges, starting on the target quit day (TQD). Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Extended Duration Combination NRT; Behavioral: Minimal Counseling

24-week C-NRT with 4-Week Preparation C-NRT and Minimal Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Then, starting on the TQD, participants will receive 24 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.

Drug: Preparation Combination NRT and Extended Duration Combination NRT; Behavioral: Minimal Counseling

12-week C-NRT with Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 12 weeks of nicotine patches and nicotine mini-lozenges to use starting on their quit day. Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Standard Duration Combination NRT; Behavioral: Intensive Counseling

12-week C-NRT with 4-Week Preparation C-NRT and Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Starting on the TQD, participants will receive 12 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke \>10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Preparation Combination NRT and Standard Duration Combination NRT; Behavioral: Intensive Counseling

24-week C-NRT with Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 24 weeks of nicotine patches and nicotine mini-lozenges, starting on the target quit day (TQD). Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Extended Duration Combination NRT; Behavioral: Intensive Counseling

24-week C-NRT with 4-Week Preparation C-NRT and Intensive Counseling

ACTIVE COMPARATOR

Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Starting on the TQD, participants will receive 24 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke \>10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.

Drug: Preparation Combination NRT and Extended Duration Combination NRT; Behavioral: Intensive Counseling

Interventions

Preparation Varenicline and Standard Duration Varenicline DRUG

16 weeks of varenicline starting 4 weeks pre-quit

12-week Varenicline with 4-Week Preparation Varenicline and Intensive Counseling; 12-week Varenicline with 4-Week Preparation Varenicline and Minimal Counseling

Preparation Varenicline and Extended Duration Varenicline DRUG

28 weeks of varenicline starting 4 weeks pre-quit

24-week Varenicline with 4-Week Preparation Varenicline and Intensive Counseling; 24-week Varenicline with 4-Week Preparation Varenicline and Minimal Counseling

Standard Duration Varenicline DRUG

12 weeks of varenicline

12-week Varenicline with Intensive Counseling; 12-week Varenicline with Minimal Counseling

Extended Duration Varenicline DRUG

24 weeks of varenicline

24-week Varenicline with Intensive Counseling; 24-week Varenicline with Minimal Counseling

Preparation Combination NRT and Standard Duration Combination NRT DRUG

16 weeks of nicotine patch + nicotine mini-lozenge starting 4 weeks pre-quit

12-week C-NRT with 4-Week Preparation C-NRT and Intensive Counseling; 12-week C-NRT with 4-Week Preparation C-NRT and Minimal Counseling

Preparation Combination NRT and Extended Duration Combination NRT DRUG

28 weeks of nicotine patch + nicotine mini-lozenge starting 4 weeks pre-quit

24-week C-NRT with 4-Week Preparation C-NRT and Intensive Counseling; 24-week C-NRT with 4-Week Preparation C-NRT and Minimal Counseling

Standard Duration Combination NRT DRUG

12 weeks of nicotine patch + nicotine mini-lozenge

12-week C-NRT with Intensive Counseling; 12-week C-NRT with Minimal Counseling

Extended Duration Combination NRT DRUG

24 weeks of nicotine patch + nicotine mini-lozenge

24-week C-NRT with Intensive Counseling; 24-week C-NRT with Minimal Counseling

Intensive Counseling BEHAVIORAL

4 phone or video counseling sessions

12-week C-NRT with 4-Week Preparation C-NRT and Intensive Counseling; 12-week C-NRT with Intensive Counseling; 12-week Varenicline with 4-Week Preparation Varenicline and Intensive Counseling; 12-week Varenicline with Intensive Counseling; 24-week C-NRT with 4-Week Preparation C-NRT and Intensive Counseling; 24-week C-NRT with Intensive Counseling; 24-week Varenicline with 4-Week Preparation Varenicline and Intensive Counseling; 24-week Varenicline with Intensive Counseling

Minimal Counseling BEHAVIORAL

2 brief phone or video counseling sessions

12-week C-NRT with 4-Week Preparation C-NRT and Minimal Counseling; 12-week C-NRT with Minimal Counseling; 12-week Varenicline with 4-Week Preparation Varenicline and Minimal Counseling; 12-week Varenicline with Minimal Counseling; 24-week C-NRT with 4-Week Preparation C-NRT and Minimal Counseling; 24-week C-NRT with Minimal Counseling; 24-week Varenicline with 4-Week Preparation Varenicline and Minimal Counseling; 24-week Varenicline with Minimal Counseling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Smoking \>4 cigarettes/day for the previous 6 months
• Able to read, write, and speak English
• If currently using nicotine replacement therapy (NRT), agreeing to use only study medication for the duration of the study
• Medically eligible to use study medications
• If the participant is a woman of childbearing potential, using an approved method of birth control during treatment

You may not qualify if:

• Currently taking bupropion or varenicline
• Suicidal ideation in the last 12 months or any suicide attempts in the past 10 years

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Wisconsin Center for Tobacco Research and Intervention

Madison, Wisconsin, 53711, United States

Location

UW Center for Tobacco Research and Intervention

Milwaukee, Wisconsin, 53233, United States

Location

Related Publications (1)

• Theodoulou A, Chepkin SC, Ye W, Fanshawe TR, Bullen C, Hartmann-Boyce J, Livingstone-Banks J, Hajizadeh A, Lindson N. Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2023 Jun 19;6(6):CD013308. doi: 10.1002/14651858.CD013308.pub2.

  PMID: 37335995 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

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

Study Officials

• Megan E Piper, PhD

  University of Wisconsin, Madison

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Daily smokers will be recruited from primary care to participate in a fully crossed, 2x2x2x2 factorial experiment (N=608) that evaluates 4 different factors: 1) Medication Type (Varenicline vs. Combination NRT \[C-NRT\]), 2) Preparation Medication (4 Weeks vs. Standard), 3) Medication Duration (Extended \[24 weeks\] vs. Standard \[12 weeks\]); and 4) Counseling (Intensive vs. Minimal).

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: December 6, 2019
• Study Start: December 10, 2020
• Primary Completion: May 8, 2025
• Study Completion: May 8, 2025
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication of the main findings
• Access Criteria: Approval of a data request by the investigators

Locations

US (2)