Grant Number:	1R01CA278938-01A1 Interpret this number
Primary Investigator:	Cinciripini, Paul
Organization:	University Of Tx Md Anderson Can Ctr
Project Title:	Comparative Effectiveness of Sequential Pharmacotherapeutic Strategies and Virtually Delivered Treatment to Optimize Smoking Cessation
Fiscal Year:	2024

PROJECT SUMMARY There is a critical need for treatment approaches that conveniently deliver evidence-based interventions of counseling and pharmacotherapy to a wide range of smokers, and address the complex timeline of cessation attempt, failure, and re-attempt. The objective of this proposal is to identify the best individualized pharmacological treatment strategies used for both initial smoking cessation and for rescue therapy among those who fail to quit or relapse. The trial will use a SMART design (Sequential Multiple Assignment Randomized Trial) to estimate the comparative effectiveness of (1) an initial 6-week course of either standard dose varenicline or dual nicotine replacement (our two best performing pharmacotherapies), and (2) among those smokers who initially fail to quit after the first 6 weeks, to estimate the effects of either continuing on same medication for another 6 weeks, switching to the medication they did not receive initially, or augmenting current pharmacotherapy by increasing the dose or adding additional FDA-approved cessation medications. All treatments will occur via a virtual delivery method ensuring the widest possible application with the fewest barriers and will include both dynamic pharmacotherapy and counseling delivered in a unified environment to enhance uptake, effectiveness, and patient experience. The proposed trial will include 2000 adult participants from throughout Texas who are seeking to quit smoking. Participants will be initially randomly assigned to one of our two best-performing smoking cessation treatments, either dual nicotine replacement therapy (NRT; nicotine patch plus lozenge) or varenicline (2 mg/twice daily). After 6 weeks, smoking abstainers will remain on their current treatment and non-abstainers will be re-randomized to either (a) switch therapies (i.e., receive the treatment not given in the first 6 weeks), (b) augment their current therapy (change dosage and/or add other medications, e.g., bupropion), or (c) continue the same medication for 6 more weeks. The treatments will function as comparators with each other at the selected timepoints specific to each treatment phase. Our primary outcomes will be biochemically verified (carbon monoxide <6 ppm) continuous smoking abstinence at Week 6 and at end-of-treatment (EOT) + 30 days. Our secondary outcomes include 6-month abstinence, and withdrawal, craving, positive and negative affect, and depressive symptoms (anhedonia) Week 6 and at end- of-treatment (EOT) + 30 days. Our results will inform the patient-provider discussion on the optimal treatment approach of the future dissemination of our findings. This addresses a critical gap in treating nicotine dependence because while the majority of smokers relapse within two weeks of an initial cessation attempt there is little empirical evidence to guide clinicians or patients on the best subsequent treatment to enhance the likelihood of cessation. Our study sample will be representative of the general population of smokers, drawing volunteers from diverse community sources as well from disadvantaged populations (Medicaid eligible, rural, and uninsured).





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