A Randomized Factorial Trial of Varenicline, Nicotine Lozenges, and Smartphone Medication Adherence Reminders for Smoking Cessation: Protocol for the COMBO II Study.
8 affiliations
- 1TSET Health Promotion Research Center, Stephenson Cancer Center, University of Oklahoma Health Campus, 655 Research Parkway, Oklahoma City, OK, 73104, United States, 1 (405) 271-6872.
- 2Department of Internal Medicine, University of Oklahoma Health Campus, Tulsa, OK, United States.
- 3Department of Behavioral and Social Sciences and Center for Alcohol and Addiction Studies, Brown University School of Public Health, Providence, RI, United States.
- 4Department of Medicine, Alpert Medical School, Brown University, Providence, RI, United States.
- 5Department of Family and Preventive Medicine, University of Oklahoma Health Campus, Oklahoma City, OK, United States.
- 6Department of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Campus, Oklahoma City, OK, United States.
- 7Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Campus, Oklahoma City, OK, United States.
- 8College of Pharmacy, University of Oklahoma Health Campus, Oklahoma City, OK, United States.
Abstract
Background
Smoking remains the leading preventable cause of cancer mortality in the United States. Varenicline is the most effective monotherapy for smoking cessation, and combining it with nicotine replacement therapy (NRT) may further improve cessation rates. Smartphone-based medication adherence interventions could enhance pharmacotherapy adherence and cessation outcomes.Objective
This trial will evaluate the efficacy of varenicline plus nicotine lozenges and a smartphone adherence intervention for promoting smoking cessation.Methods
This fully remote, 2 × 2 factorial randomized controlled trial will enroll 496 adults from Oklahoma who smoke cigarettes daily. Participants will be randomized to 1 of 4 conditions: (1) varenicline (VAR) + nicotine lozenges (NRT) versus VAR alone and (2) a smartphone-based smoking cessation app with adherence components (COMBO-A [adherence]) or without adherence components (COMBO-B [basic]). The primary outcomes are biochemically verified 7-day point prevalence abstinence at 26 weeks post quit date and medication adherence during the treatment period. Secondary outcomes include withdrawal symptoms and medication side effects over the 12-week treatment period.Results
Study recruitment began in July 2026. As of the date of this paper's submission, 8 participants have been enrolled. Enrollment is expected to be completed by December 2028, with primary data collection and follow-up completed by June 2029. Primary study results are anticipated later in 2029.Conclusions
If effective, VAR+NRT would offer a new evidence-based cessation treatment option. If the smartphone adherence intervention improves medication adherence and cessation, it could be adapted for other pharmacotherapies and widely implemented. Ultimately, this research aims to enhance cessation efforts and reduce cancer risk among adults who smoke.
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BibTeX
@article{machado2026randomized,
title = {{A Randomized Factorial Trial of Varenicline, Nicotine Lozenges, and Smartphone Medication Adherence Reminders for Smoking Cessation: Protocol for the COMBO II Study.}},
author = {Nathalia M Machado and Jasjit S Ahluwalia and Michael S Businelle and Summer G Frank-Pearce and Irina Baranskaya and Emily T Hébert and Munjireen S Sifat and Shannon H Gwin and Roma Thakur and Sharon Glassman and Henry W Kinnard and Gaurav Kumar and Deeksha Gupta and Darla E Kendzor},
journal = {JMIR research protocols},
year = {2026},
month = nov,
doi = {10.2196/108379},
url = {https://europepmc.org/article/MED/42970756},
note = {CC BY},
}
RIS
TY - JOUR
TI - A Randomized Factorial Trial of Varenicline, Nicotine Lozenges, and Smartphone Medication Adherence Reminders for Smoking Cessation: Protocol for the COMBO II Study.
AU - Nathalia M Machado
AU - Jasjit S Ahluwalia
AU - Michael S Businelle
AU - Summer G Frank-Pearce
AU - Irina Baranskaya
AU - Emily T Hébert
AU - Munjireen S Sifat
AU - Shannon H Gwin
AU - Roma Thakur
AU - Sharon Glassman
AU - Henry W Kinnard
AU - Gaurav Kumar
AU - Deeksha Gupta
AU - Darla E Kendzor
PY - 2026
DA - 2026/11/02
JO - JMIR research protocols
DO - 10.2196/108379
UR - https://europepmc.org/article/MED/42970756
AB - Background Smoking remains the leading preventable cause of cancer mortality in the United States. Varenicline is the most effective monotherapy for smoking cessation, and combining it with nicotine replacement therapy (NRT) may further improve cessation rates. Smartphone-based medication adherence interventions could enhance pharmacotherapy adherence and cessation outcomes.Objective This trial will evaluate the efficacy of varenicline plus nicotine lozenges and a smartphone adherence intervention for promoting smoking cessation.Methods This fully remote, 2 × 2 factorial randomized controlled trial will enroll 496 adults from Oklahoma who smoke cigarettes daily. Participants will be randomized to 1 of 4 conditions: (1) varenicline (VAR) + nicotine lozenges (NRT) versus VAR alone and (2) a smartphone-based smoking cessation app with adherence components (COMBO-A [adherence]) or without adherence components (COMBO-B [basic]). The primary outcomes are biochemically verified 7-day point prevalence abstinence at 26 weeks post quit date and medication adherence during the treatment period. Secondary outcomes include withdrawal symptoms and medication side effects over the 12-week treatment period.Results Study recruitment began in July 2026. As of the date of this paper's submission, 8 participants have been enrolled. Enrollment is expected to be completed by December 2028, with primary data collection and follow-up completed by June 2029. Primary study results are anticipated later in 2029.Conclusions If effective, VAR+NRT would offer a new evidence-based cessation treatment option. If the smartphone adherence intervention improves medication adherence and cessation, it could be adapted for other pharmacotherapies and widely implemented. Ultimately, this research aims to enhance cessation efforts and reduce cancer risk among adults who smoke.
SN - 1929-0748
ER -