EVarQuit: Extended Pre-quit Varenicline to Assist in Quitting Smoking (EVarQuit)

Varenicline is the most effective smoking cessation therapy available. Nevertheless, most smokers using varenicline relapse within the first few months after quitting. Varenicline is hypothesized to help smokers to quit in part by reducing the reinforcing effects of smoking during the standard 1-week pre-quitting treatment phase. Learning theory and previous human and animal research support the hypothesis that a longer period of varenicline treatment prior to the target quit date (TQD) will lead to greater reductions in smoking before quitting, and higher long-term cessation rates, compared to standard varenicline treatment. Building on promising preliminary clinical data, the study tests these hypotheses with a full-scale randomized clinical trial (RCT). 320 treatment-seeking smokers will be randomized to a standard run-in group (3 weeks of placebo, followed by the standard 1 week of pre-TQD varenicline) or an extended run-in group (4 weeks of pre-TQD varenicline). Both groups will receive brief individual cessation counseling and 11 weeks of post-TQD varenicline. The primary outcome measure will be bio-verified continuous abstinence at end-of-treatment (weeks 8-11 post-quit; cessation at 26-weeks post TQD will also be examined. Hypothesized mediating mechanisms (e.g., smoking reinforcement) will be evaluated by behavioral, physiological, and subjective measures assessed both in the lab and using real-world, real-time electronic momentary assessments (EMA). The investigators predict that long-term, bio-verified smoking cessation will be improved among the extended run-in group compared to the standard run-in group. The investigators further predict the improved clinical outcomes with extended run-in varenicline will be explained (or mediated) by greater pre-quit reductions in smoking reinforcement among the extended run-in group compared to the standard run-in group. The significance of this work is clear: The project aims to make best available treatment for smoking cessation even better, using a method that is ripe for dissemination and an approach that will elucidate critical mechanisms to target in the next generation of treatment enhancement.

Study Overview

• Status: Completed
• Conditions: Tobacco Smoking
• Intervention / Treatment: Drug: Varenicline; Behavioral: Brief smoking cessation counseling

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14260
      • State University of New York at Buffalo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Smoking at least 10 cigarettes per day (CPD) for the past 6 months and expired-air carbon monoxide (CO) >7 at intake. NOTE: To reduce exclusion of Black participants, the CPD criterion was reduced to 5 and the carbon monoxide criterion was eliminated in November, 2019.
• At least moderately motivated to quit smoking and intention to make a quit attempt with varenicline 1 month after treatment begins.
• Planning to remain in western New York (NY) during the study period
• Willing to use varenicline and to refrain from other cessation treatments and tobacco products during the study period.
• English speaker
• To be intent-to-treat (ITT), the participant must complete Lab Visit 1 and meet minimal completion rate for real-world (EMA) assessments.

Exclusion Criteria:

• Use of other tobacco products, including e-cigarettes, in past 7 days
• Use of smoking cessation medication, including nicotine replacement therapy, in the past 14 days
• Prior allergy/hypersensitivity to varenicline
• Pregnant or breast-feeding

• Substance use:

  • Alcohol: AUDIT score > 15 at intake, suggestive of alcohol dependence and warranting treatment; for those with scores between 8 and 15, the investigators will advise reducing drinking).
  • Medical treatment for substance use (SU) in past 3 months, including Suboxone (buprenorphine) and methadone (at phone screen)

  • Using a combination of the National Institute on Drug Abuse (NIDA) modified ASSIST (4-26 = moderate risk; 27+ = high risk) and urine toxicology screen (both at intake):

    • Cannabis: ASSIST=27+ (tox screen not used)
    • Cocaine: ASSIST=7+ OR positive tox screen
    • Methamphetamine: ASSIST=7+ OR positive tox screen
    • Inhalants, hallucinogens, sedatives, or sleeping pills: ASSIST score = 7+
    • Prescription stimulants: With prescription, ASSIST 27+; Without prescription, ASSIST 7+
    • Opioids: With prescription, ASSIST 27+ (note ineligible if prescription is for buprenorphine or methadone); Without prescription, ASSIST 7+ OR positive tox screen

(Note: ASSIST 4+ modified to 7+ in 2018 to avoid excluding people with past SU problems. clinicaltrials.gov edited 12/18/18)

• Psychiatric:

  • Antipsychotic medications
  • Lifetime history of schizophrenia or bipolar disorder
  • Evidence of current major depression (per Patient Health Questionnaire (PHQ-9) at intake
  • Past 10 years suicidal ideation (SI) / behavior. At intake, all of the following are exclusionary on the baseline Columbia-Suicide Severity Rating Scale (Posner et al., 2008): SI without intent (C-SSRS #1, #2, or #3), if any intensity rating (Frequency, Duration, Controllability, Deterrents, or Reasons for Ideation) is > 2; SI with intent (C-SSRS #4, or #5), regardless of intensity ratings; Suicidal Behavior (any suicide attempt, interrupted attempt, aborted attempt, or suicide preparatory acts or behavior on the C-SSRS).
• Any medical condition, illness, disorder or concomitant medication that compromises participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
• Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extended Run-In; ** 4 weeks of varenicline prior to the target quit date (TQD) ** + 11 weeks of post-TQD varenicline Standard varenicline dosing titration in initial week of therapy (one 0.5 mg tablet orally daily x 3 days, then one 0.5 mg tablet twice daily x 4 days); then 1 mg twice daily thereafter. Brief individual counseling at clinic visits	Drug: Varenicline; oral varenicline tablets; Other Names: Chantix; Behavioral: Brief smoking cessation counseling; ~10-minute individual counseling at each of 6 clinic visits
Active Comparator: Standard Run-In; ** 3 weeks of placebo followed by 1 week of varenicline prior to the target quit date (TQD) ** + 11 weeks of post-TQD varenicline Standard varenicline dosing titration in initial week of therapy (one 0.5 mg tablet orally daily x 3 days, then one 0.5 mg tablet twice daily x 4 days); then 1 mg twice daily thereafter. Brief individual counseling at clinic visits	Drug: Varenicline; oral varenicline tablets; Other Names: Chantix; Behavioral: Brief smoking cessation counseling; ~10-minute individual counseling at each of 6 clinic visits

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Continuous Abstinence at End-of-Treatment (EOT) as Assessed by Self-Report and Bio-verification	Number of participants with bio-verified (cotinine level of 15 ng/mL or less) self-reported continuous abstinence from smoking (not even a puff) during the final four weeks of treatment	Self-report Treatment Weeks 12-15; bio-verification ~Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-quit Change in Cigarettes Smoked Per Day	Percent change in smoking behavior (self-reported cigarettes per day; CPD) from timeline follow-back (TLFB) interviews during the pre-quit phase of the study.	Treatment Week 1 vs. Treatment Week 4 (final week before TQD)
Number of Participants With Continuous Abstinence at 6-Month Follow-Up as Assessed by Self-Report and Bio-verification	Number of participants with continuous abstinence at the 6-month follow-up (no self-reported smoking during weeks 12-28 AND cotinine level 15 ng/mL or less at EOT and 6 month follow-up)	Self-report Treatment Weeks 12-28; bio-verification ~Week 16 and ~Week 29

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: National Cancer Institute (NCI); Pfizer

Publications and helpful links

General Publications

• Hawk LW Jr, Tiffany ST, Colder CR, Ashare RL, Wray JM, Tyndale RF, Brandon TH, Mahoney MC. Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241731. doi: 10.1001/jamanetworkopen.2022.41731.
• Ferkin AC, Tonkin SS, Maguin E, Mahoney MC, Colder CR, Tiffany ST, Hawk LW. A Psychometric Evaluation of the Stanford Expectations of Treatment Scale (SETS) in the Context of a Smoking Cessation Trial. Nicotine Tob Res. 2022 Nov 12;24(12):1914-1920. doi: 10.1093/ntr/ntac187.
• Mahoney MC, Park E, Schlienz NJ, Duerr C, Hawk LW. Transitioning to Remote Clinic Visits in a Smoking Cessation Trial During the COVID-19 Pandemic: Mixed Methods Evaluation. JMIR Form Res. 2021 Apr 30;5(4):e25541. doi: 10.2196/25541.
• Lawson SC, Gass JC, Cooper RK Jr, Tonkin SS, Colder CR, Mahoney MC, Tiffany ST, Hawk LW Jr. The impact of three weeks of pre-quit varenicline on reinforcing value and craving for cigarettes in a laboratory choice procedure. Psychopharmacology (Berl). 2021 Feb;238(2):599-609. doi: 10.1007/s00213-020-05713-7. Epub 2020 Nov 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): April 5, 2021
• Study Completion (Actual): July 8, 2021

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 25, 2017

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: STUDY00000911; R01CA206193 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share study data through the NIDA-supported NAHDAP repository. IPD to be shared include baseline participant characteristics, intervention group, smoking abstinence, and adverse events.
• IPD Sharing Time Frame: 2023. We are currently awaiting confirmation from NAHDAP that our archival plan fits their expectations. Data will be available indefinitely (as long as NAHDAP is supported).
• IPD Sharing Access Criteria: Public release; anyone who registers on the website.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No