VergeRx for Smokers Not Ready to Quit

Optimizing Pharmacist-Led Tobacco Treatment for Individuals Who Smoke and Are Not Ready to Make a Quit Attempt in Federally-Qualified Health Centers

This study uses a factorial optimization experiment to identify which treatment components help adults who smoke and are not ready to quit in the next 30 days (smokers not ready to quit, or SNRTQ) achieve smoking cessation. Participants are recruited through Federally Qualified Health Centers (FQHCs) in Virginia and West Virginia. All participants receive at least 8 weeks of nicotine replacement therapy (NRT) patch. Using a 2×2×2×2 factorial design, the study independently tests four components: a pharmacist-delivered behavioral program (VergeRx), a text-message support program (SmokefreeTXT), the addition of an NRT lozenge to the patch, and an extended 16-week course of the NRT patch versus the standard 8 weeks. The goal is to estimate the effect of each component on biochemically confirmed smoking abstinence so that an optimized treatment package can be assembled. The primary outcome is abstinence at 26 weeks; a secondary outcome is abstinence at 52 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Tobacco Use Cessation
• Intervention / Treatment: Behavioral: VergeRx; Behavioral: SmokefreeTXT; Drug: NRT Lozenge (Combination); Drug: Extended NRT Patch (16 weeks); Drug: Standard NRT Patch (8 weeks)

Detailed Description

Background and rationale. People who smoke but are not ready to quit in the next 30 days (SNRTQ) are underserved by conventional cessation treatments, which typically require a near-term commitment to quit. Substantial questions remain about how best to treat this population, including whether combination NRT outperforms monotherapy for these smokers and how long NRT patch treatment should be provided. This study applies the optimization phase of the Multiphase Optimization Strategy (MOST) to efficiently evaluate multiple candidate components within a single experiment, guided by a Phase-Based Framework for smoking cessation.

Design. The study is a fully-crossed 2×2×2×2 factorial experiment with 16 treatment conditions and a planned enrollment of 592 participants (~37 per condition). Four components are independently randomized:

VergeRx (yes vs. no): Participants receive up to three pre-quit modules with a local pharmacist or pharmacy technician to promote NRT adherence. Readiness to quit is assessed at weekly REDCap check-ins conducted by the research team; participants may also report readiness to their pharmacist during or between sessions. Upon reporting readiness, participants advance to six treatment sessions delivered over four weeks. If readiness is not reported after four weekly check-ins, the VergeRx component ends.

SmokefreeTXT (yes vs. no): Participants receive up to three 7-day pre-quit modules ("Daily Challenges") to prepare for a quit attempt. Upon reporting readiness at a weekly check-in, participants transition to the SmokefreeTXT program, which delivers 3-5 messages per day for seven weeks. If readiness is not reported after four weekly check-ins, the component ends.

Combination NRT Lozenge + NRT Patch (vs. patch alone): Participants assigned to this component receive nicotine lozenge in addition to the NRT patch, testing whether combining delivery mechanisms improves outcomes relative to patch monotherapy in this population.

16 weeks of NRT patch (vs. standard 8 weeks): This factor tests whether an extended patch duration improves cessation relative to the standard 8-week course.

All participants receive at least 8 weeks of NRT patch beginning in Week 1. Recruitment. Participants are referred by physicians and pharmacists at their local FQHC through an ask-advise-connect model, supplemented by advertisements placed around the FQHC. Eligible participants do not intend to quit in the next 30 days, a motivational cutoff based on prior literature.

Analysis. Consistent with the factorial/MOST approach, the 16 conditions are not compared individually. The main effect of each component is estimated by pooling data across all conditions-for example, the main effect of VergeRx compares abstinence among the ~296 participants who received it against the ~296 who did not. This design uses data from all participants to estimate each component's main effect, providing adequate statistical power with approximately 37 participants per condition. A conceptual model based on the Phase-Based Framework specifies the mediating constructs (proximal outcomes) through which the components are hypothesized to influence cessation, and these mediators are assessed alongside the cessation outcomes.

Outcomes. The primary outcome is biochemically confirmed point-prevalence cigarette abstinence at the 26-week follow-up. A secondary outcome is biochemically confirmed point-prevalence abstinence at the 52-week follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 592
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Melissa A Little; Phone Number: 4349241935; Email: mal7uj@virginia.edu

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22904
      • University of Virginia
      • Contact: Melissa Little; Phone Number: 434-924-1935; Email: mal7uj@virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Not ready to quit smoking in the next 30 days
• Age ≥ 18 years
• Able to read, speak, and understand English
• Report smoking ≥ 5 cigarettes per day for the past 6 months
• Own a cell phone
• Willing and able to use nicotine replacement therapy (NRT) in the form of patch and lozenge

Exclusion Criteria:

• Currently pregnant, or planning to become pregnant in the next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VergeRx + SmokefreeTXT + 16-wk Patch + Lozenge; VergeRx; SmokefreeTXT; Extended NRT Patch (16 wk); NRT Lozenge	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: NRT Lozenge (Combination); Nicotine lozenge provided in addition to the NRT patch (combination NRT vs. patch monotherapy).; Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: VergeRx + SmokefreeTXT + 16-wk Patch; VergeRx; SmokefreeTXT; Extended NRT Patch (16 wk)	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: VergeRx + SmokefreeTXT + 8-wk Patch + Lozenge; VergeRx; SmokefreeTXT; Standard NRT Patch (8 wk); NRT Lozenge	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: NRT Lozenge (Combination); Nicotine lozenge provided in addition to the NRT patch (combination NRT vs. patch monotherapy).; Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: VergeRx + SmokefreeTXT + 8-wk Patch; VergeRx; SmokefreeTXT; Standard NRT Patch (8 wk)	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: VergeRx + 16-wk Patch + Lozenge; VergeRx; Extended NRT Patch (16 wk); NRT Lozenge	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: NRT Lozenge (Combination); Nicotine lozenge provided in addition to the NRT patch (combination NRT vs. patch monotherapy).; Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: VergeRx + 16-wk Patch	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: VergeRx + 8-wk Patch + Lozenge; VergeRx; Standard NRT Patch (8 wk); NRT Lozenge	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: NRT Lozenge (Combination); Nicotine lozenge provided in addition to the NRT patch (combination NRT vs. patch monotherapy).; Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: VergeRx + 8-wk Patch; VergeRx; Standard NRT Patch (8 wk)	Behavioral: VergeRx; Up to three pre-quit modules delivered by a local pharmacist/technician to promote NRT adherence; upon reported readiness to quit (assessed at weekly REDCap check-ins), participants advance to six treatment sessions over four weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: SmokefreeTXT + 16-wk Patch + Lozenge; SmokefreeTXT; Extended NRT Patch (16 wk); NRT Lozenge	Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: NRT Lozenge (Combination); Nicotine lozenge provided in addition to the NRT patch (combination NRT vs. patch monotherapy).; Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: SmokefreeTXT + 16-wk Patch; SmokefreeTXT; Extended NRT Patch (16 wk)	Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: SmokefreeTXT + 8-wk Patch + Lozenge; SmokefreeTXT; Standard NRT Patch (8 wk); NRT Lozenge	Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: NRT Lozenge (Combination); Nicotine lozenge provided in addition to the NRT patch (combination NRT vs. patch monotherapy).; Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: SmokefreeTXT + 8-wk Patch; SmokefreeTXT; Standard NRT Patch (8 wk)	Behavioral: SmokefreeTXT; Up to three 7-day pre-quit "Daily Challenges" text modules; upon reported readiness to quit, the SmokefreeTXT program delivers 3-5 messages/day for seven weeks. Component ends if readiness is not reported after four weekly check-ins.; Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: 16-wk Patch + Lozenge; Extended NRT Patch (16 wk); NRT Lozenge	Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: 16-wk Patch; Extended NRT Patch (16 wk)	Drug: Extended NRT Patch (16 weeks); Nicotine patch provided for 16 weeks.
Experimental: 8-wk Patch + Lozenge; Standard NRT Patch (8 wk); NRT Lozenge	Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).
Experimental: 8-wk Patch (reference); Standard NRT Patch (8 wk)	Drug: Standard NRT Patch (8 weeks); Nicotine patch provided for 8 weeks (all participants receive at least 8 weeks of patch beginning Week 1).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemically confirmed 7-day point prevalence cigarette abstinence at 26 weeks	Point prevalence abstinence, defined as no cigarette smoking (not even a puff) within the past 7 days, biochemically confirmed using a CoVita Smokerlyzer carbon monoxide (CO) monitor at the FQHC. Participants unable to travel who report no combustible tobacco use are mailed a cotinine test completed via Zoom. Participants who do not provide outcome data are classified as smoking.	26 weeks after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemically confirmed 7-day point prevalence cigarette abstinence at 52 weeks	Same definition and biochemical confirmation procedure as the primary outcome (no smoking within the past 7 days; CO-verified, with mailed cotinine confirmation via Zoom when travel is not possible; missing data classified as smoking), assessed at the 52-week follow-up to evaluate cessation maintenance.	52 weeks after enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motivation to quit	Self-reported motivation/readiness to quit smoking, assessed by questionnaire at each assessment point.	Baseline through 52 weeks
Cigarettes smoked per day	Self-reported number of cigarettes smoked per day.	Baseline through 52 weeks
Adherence to NRT	Adherence measured as the percentage of dispensed NRT patch and/or lozenge that was used.	Weeks 1 through 52
Frequency of urges to smoke	Self-reported frequency of urges to smoke (Strength of Urges to Smoke measure).	Baseline through 52 weeks
Strength of urges to smoke	Self-reported strength/intensity of urges to smoke.	Baseline through 52 weeks
Quit attempts	Number of quit attempts, where a quit attempt is defined as cigarette abstinence for ≥ 24 hours not due to involuntary cessation.	Baseline through 52 weeks
Time to first NRT use (NRT uptake)	Time from enrollment (when the prescription is pushed to the pharmacy via REDCap) to first use of NRT, capturing timely initiation of medication, distinct from ongoing adherence.	Week 1 check-in
Program satisfaction	Participant-reported barriers to treatment utilization, satisfaction with treatment components, and suggestions for improvement, using open- and closed-ended items focused on perceived capacity and opportunity to engage with the interventions.	11 weeks

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Melissa Little, PhD, MPH, University of Virginia

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2027
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): November 1, 2032

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: smoking cessation; urban; rural; pharmacists; low income; federally qualified health center; smokers not ready to quit; medicaid; appalachia; readiness to quit
• Additional Relevant MeSH Terms: Behavior; Health Behavior; Smoking Cessation; Tobacco Use Cessation
• Other Study ID Numbers: HSR303823

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plans to share data at the individual level

Drug and device information, study documents

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