Effectiveness of Combination Varenicline and Oral Nicotine Replacement Therapy (COMBO)

NCT03722966 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 10184
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Varenicline is considered to be a first-line tobacco cessation treatment. Previous studies have evaluated the impact of the combination of varenicline and nicotine patches (versus varenicline alone) on smoking cessation, though findings have been equivocal. No studies to date have evaluated the combination of varenicline and oral nicotine replacement therapy (NRT; i.e., nicotine lozenges or gum). Nicotine lozenges and gum can provide acute relief during cravings and high risk situations, which offers individuals the flexibility to deliver nicotine when they need it most (in contrast with the continuous and passive delivery of nicotine offered via the patch). Prospective clinical trials are needed in real-world settings to determine whether the combination of varenicline and oral nicotine replacement therapy (i.e., lozenges, gum) is superior to varenicline alone for smoking cessation. The proposed pilot randomized trial would enroll 100 participants over 1 year (≈8 participants per month) utilizing a 2x2 factorial design. Twelve weeks of a pharmacological intervention \[varenicline + oral NRT (VAR+N) vs. varenicline alone (VAR)\] will be crossed with automated medication reminders (reminder messages vs. no reminder messages). All participants will receive an adapted version of the standard counseling offered through the Tobacco Treatment Research Program (TTRP). The primary outcomes will be biochemically-verified smoking cessation at 12 and 26 weeks following a scheduled quit attempt (1 week after enrollment). Smartphone-based ecological momentary assessment (EMA) will be employed to measure withdrawal symptoms, medication adherence, side effects, and adverse events using the Insight™ platform developed by the Stephenson Cancer Center (SCC) mHealth Shared Resource. This pilot study will provide information regarding the feasibility, acceptability, and preliminary efficacy of combination varenicline and oral NRT for smoking cessation, which will support an NIH funding application for a larger, adequately powered study.

Conditions

Smoking Cessation

Keywords

smoking cessation; varenicline; nicotine gum; nicotine lozenges; nicotine replacement therapy; adherence; mHealth

Outcome Measures

Primary Outcomes (2)

• Biochemically-Verified Smoking Cessation

  Self-reported abstinence over the prior 7-days with a carbon monoxide value \<7 ppm (in exhaled breath) at 12 weeks post-quit date

  12 weeks post-quit date

• Biochemically-Verified Smoking Cessation

  Self-reported abstinence over the prior 7-days in conjunction with a carbon monoxide value \<7 ppm (in exhaled breath) at 26 weeks post-quit date

  26 weeks post-quit date

Secondary Outcomes (2)

• Varenicline Adherence

  1 week pre-quit though 12 weeks following a scheduled quit date (13 weeks)

• Oral NRT Adherence

  12 weeks post-quit date

Study Arms (4)

Varenicline/Counseling + Med Reminders (VAR+REM)

EXPERIMENTAL

Participants will receive behavioral tobacco cessation counseling, a 13-week course of varenicline, and automated medication reminders via their smartphones.

Drug: Varenicline; Behavioral: Medication Reminders; Behavioral: Tobacco Cessation Counseling

Varenicline/Counseling (VAR+NREM)

EXPERIMENTAL

Participants will receive behavioral tobacco cessation counseling, a 13-week course of varenicline, and no automated medication reminders.

Drug: Varenicline; Behavioral: Tobacco Cessation Counseling

Varenicline/Counseling + Oral NRT (VAR+NRT+NREM)

EXPERIMENTAL

Participants will receive behavioral tobacco cessation counseling, a 13-week course of varenicline, 12 weeks of oral nicotine replacement therapy (NRT; gum or lozenge), and no automated medication reminders.

Drug: Varenicline; Drug: Oral Nicotine Replacement Therapy (NRT); Behavioral: Tobacco Cessation Counseling

Varenicline/Counseling + Oral NRT + Med Reminders (VAR+NRT+REM)

EXPERIMENTAL

Participants will receive behavioral tobacco cessation counseling, a 13-week course of varenicline, 12 weeks of oral nicotine replacement therapy (NRT; gum or lozenge), and automated medication reminders via their smartphones.

Drug: Varenicline; Drug: Oral Nicotine Replacement Therapy (NRT); Behavioral: Medication Reminders; Behavioral: Tobacco Cessation Counseling

Interventions

Varenicline DRUG

All participants will be offered a 13-week course of varenicline (including a 1 week titration period). Dosage and administration per manufacturer: 0.5mg once daily for days 1-3 and 0.5mg twice daily for days 4-7 encompass the titration period, then 1mg twice daily for 12 weeks. An additional 12 weeks of treatment is recommended for long-term abstinence.

Also known as: Chantix

Varenicline/Counseling (VAR+NREM); Varenicline/Counseling + Med Reminders (VAR+REM); Varenicline/Counseling + Oral NRT (VAR+NRT+NREM); Varenicline/Counseling + Oral NRT + Med Reminders (VAR+NRT+REM)

Oral Nicotine Replacement Therapy (NRT) DRUG

Half of study participants will be randomly assigned to receive oral nicotine replacement therapy (4mg gum or 4mg lozenge, depending on preference; to be used every 1-2 hours as urges occur) in addition to varenicline.

Also known as: Nicotine Gum (4mg), Nicotine Lozenge (4mg)

Varenicline/Counseling + Oral NRT (VAR+NRT+NREM); Varenicline/Counseling + Oral NRT + Med Reminders (VAR+NRT+REM)

Medication Reminders BEHAVIORAL

Half of study participants will be randomly assigned to receive automated medication reminders via their smartphones.

Varenicline/Counseling + Med Reminders (VAR+REM); Varenicline/Counseling + Oral NRT + Med Reminders (VAR+NRT+REM)

Tobacco Cessation Counseling BEHAVIORAL

All participants will be offered 6 weekly tobacco cessation counseling sessions with a Tobacco Treatment Specialist.

Varenicline/Counseling (VAR+NREM); Varenicline/Counseling + Med Reminders (VAR+REM); Varenicline/Counseling + Oral NRT (VAR+NRT+NREM); Varenicline/Counseling + Oral NRT + Med Reminders (VAR+NRT+REM)

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age
• ≥ 6th grade English literacy
• agree to use personal or study-provided smartphone/applications
• agree to complete phone-based or in-person surveys throughout 26 week study
• expired CO \> 6 ppm at baseline visit (suggesting current smoker)
• currently smoke ≥ 5 cigarettes per day
• willing to make quit attempt 7 days after baseline visit

You may not qualify if:

• \< 18 years of age
• history of seizures or allergic reaction to varenicline
• report current suicidality
• taking anti-depressants or anti-psychotic medications
• pregnant or planning to become pregnant
• currently breastfeeding

Sponsors & Collaborators

• University of Oklahoma: lead
• Pfizer: collaborator

Study Sites (1)

TSET Health Promotion Research Center

Oklahoma City, Oklahoma, 73104, United States

Location

Related Publications (2)

• Sifat M, Hebert ET, Ahluwalia JS, Businelle MS, Waring JJC, Frank-Pearce SG, Bryer C, Benson L, Madison S, Planas LG, Baranskaya I, Kendzor DE. Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial. JMIR Form Res. 2023 Oct 27;7:e48857. doi: 10.2196/48857.

  PMID: 37889541 RESULT

• Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.

  PMID: 34611902 DERIVED

MeSH Terms

Conditions

Smoking Cessation

Interventions

Varenicline; Nicotine Replacement Therapy; Nicotine Chewing Gum; Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Drug Therapy; Therapeutics; Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Limitations and Caveats

The study was discontinued early due to the recall of varenicline.

Results Point of Contact

• Title: Dr. Darla Kendzor
• Organization: The University of Oklahoma Health Sciences Center

Darla-Kendzor@ouhsc.edu

(405) 271-8001

Study Officials

• Darla Kendzor, PhD

  The University of Oklahoma Health Sciences Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 29, 2018
• Study Start: January 7, 2020
• Primary Completion: February 7, 2022
• Study Completion: February 7, 2022
• Last Updated: February 6, 2024
• Results First Posted: February 6, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)