Randomized Factorial Trial of Varenicline With Nicotine Lozenges and a Smartphone Medication Adherence Intervention to Promote Smoking Cessation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 496
- 试验地点
- 2
- 主要终点
- Smoking Abstinence (26 weeks post-quit)
研究概览
简要总结
No published studies to date have evaluated the combined impact of varenicline and oral nicotine replacement therapy (NRT) on smoking cessation in a randomized trial. Oral NRT, such as nicotine lozenges, can provide acute relief from cravings/withdrawal, and offers individuals the flexibility to deliver nicotine quickly, in contrast with the continuous, passive, and slow-acting delivery of the nicotine patch. Nevertheless, in clinical trials of other combination pharmacotherapies, participants' adherence to of oral NRT has been suboptimal, making it difficult to determine whether there is an added benefit. Given the near-ubiquity of smartphone ownership (85% of U.S. adults), it is plausible that smartphone-based medication adherence interventions could have a positive influence on pharmacotherapy adherence and smoking cessation. This investigative team has demonstrated the feasibility and potential efficacy of using combination varenicline plus oral NRT treatment to promote smoking cessation in a pilot factorial randomized trial. Likewise, pilot findings showed that medication adherence and smoking cessation rates were higher among those who received smartphone-based medication reminders than those who did not. The proposed study will enroll 496 adults who smoke cigarettes daily. The study will employ a 2x2 factorial design in which participants will be randomized to one of four combinations of two treatment factors: 1) pharmacological treatment (varenicline + nicotine lozenges vs. varenicline alone) and 2) smartphone medication adherence intervention (smartphone-based smoking cessation app with vs. without adherence components). The primary study outcomes will be biochemically-confirmed 7-day point prevalence abstinence at 26 weeks after a scheduled quit date, and medication adherence over the 13-week treatment period. Smartphone-based daily diaries will be employed to assess daily smoking and medication adherence. Notably, the proposed study will employ entirely remote assessment and treatment delivery strategies. Exploratory analyses will evaluate the potential interaction between medication type and the smartphone adherence intervention, and compare the influences of pharmacological treatment type and the medication adherence intervention on weekly physical symptoms (e.g., withdrawal, medication side effects). The overarching goal of the proposed research is to improve smoking cessation treatment and decrease cancer risk.
详细描述
Study Overview. The study will employ an efficient 2x2 factorial design in which participants are randomized to one of four combinations of two treatment factors: 1) pharmacological treatment (VAR+NRT or VAR) and 2) smartphone-based smoking cessation intervention with or without medication adherence intervention (COMBO-A [adherence] or COMBO-B [basic]). All participants will receive 13 weeks of varenicline including the standard 1-week pre-quit titration period, with half of participants additionally receiving 12 weeks of nicotine lozenges. Those assigned to the COMBO-A group will receive a smartphone intervention app that includes medication adherence components: education, medication reminders, medication tracking, and messages following a missed medication dose. Participants assigned to COMBO-B will receive a smartphone smoking cessation intervention app that does not include medication adherence components. All participants, regardless of treatment group assignment will receive telephone counseling with a Tobacco Treatment Specialist from the TTRP. The primary study outcomes will be carbon monoxide (CO)-confirmed 7-day point prevalence abstinence at 26 weeks after the scheduled quit date, and medication adherence during the 12-week treatment period (self-reported weekly). Daily smoking and medication adherence will also be assessed via smartphone.
Randomization Plan. Stratified block randomization, with a small block size, will be used to ensure balance between study arms over time. Randomization will be stratified by sex (male vs. female), race/ethnicity (White vs. minoritized race/ethnicity), and cigarettes smoked per day (<10 vs. ≥10). Participants will be randomized following full study enrollment.
Blinding. Participant blinding is not feasible since participants will be aware of whether or not they are provided with nicotine lozenges (in addition to the varenicline provided to all participants), and they will know whether their smartphone app has medication adherence components.
Intervention Components. Counseling. All participants will be scheduled to receive 6 weekly telephone counseling sessions lasting 15-30 minutes each with an experienced tobacco treatment specialist (TTS) though the TTRP. Counseling sessions will begin one week prior to the scheduled quit date and continue weekly through 4 weeks after the quit date. Consistent with Guideline recommendations, counseling will focus on education, skill-building, and support; and will employ cognitive-behavioral and motivational strategies. Topics include benefits of quitting, mood/stress management strategies, making positive lifestyle changes, coping skills, and planning for future challenges. Several recommended strategies will be employed to maintain and evaluate treatment fidelity (e.g., counseling checklists, session duration, and total sessions completed). Participant perceptions of nonspecific counselor characteristics will be assessed. Differences between groups on counseling factors may be included in analyses as covariates.
Varenicline. All participants will be evaluated by a study physician via telephone or video conferencing for eligibility to use varenicline. If appropriate, varenicline will be prescribed and filled through a campus Pharmacy and mailed to participants. During the week prior to the scheduled quit date, participants will begin taking varenicline. Doses will be titrated during the first week of medication use (days 1-3: 0.5 mg once daily; days 4-7: 0.5 mg twice daily) and will continue at 1 mg twice daily for 12 additional weeks. Participants will be advised to continue taking varenicline, even if they return to smoking.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able to provide documentation of identity (to prevent fraudulent enrollment) and Oklahoma residence (due to limitations on prescribing to out-of-state residents)
- •Reports daily smoking ≥5 cigarettes per day
- •Provides a breath CO sample ≥6ppm to verify current smoking
- •Willing to schedule a smoking cessation attempt within the next 1-2 weeks
- •Willing to abstain from smoking cannabis or other combustible products during the study
- •Willing to use varenicline and nicotine lozenges
- •Willing to participate in the study for ≈6 months
- •Able to demonstrate >6th grade literacy which is necessary to read intervention materials and complete study assessments
排除标准
- •Does not own a smartphone that is compatible with the study app
- •Using an FDA-approved smoking cessation medication within the past 30 days
- •Using oral nicotine products (e.g., pouches, chewing tobacco, snus) more than once per week (5+ times) during the past 30 days
- •History of seizures (varenicline contraindication)
- •History of allergic reaction to varenicline
- •Pregnant, planning to become pregnant, or currently breastfeeding
- •Unwilling or unable to use varenicline or nicotine lozenges for other reasons (e.g., severe dry mouth, past history of severe medication side effects)
- •Other medical reasons at the discretion of the prescribing physician (e.g., uncontrolled hypertension, recent myocardial infarction)
- •Weekly or more frequent use of combustible cannabis during the past 30 days with a score ≥2 on the Cannabis Use Disorder Identification Test-Short Form
研究组 & 干预措施
Varenicline + Smartphone Intervention with adherence components (VAR + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Varenicline (VAR) (Drug)
Varenicline + Smartphone Intervention with adherence components (VAR + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Smartphone intervention with adherence components (COMBO-A) (Behavioral)
Varenicline + Smartphone Intervention with adherence components (VAR + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Telephone Counseling (Behavioral)
Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Varenicline (VAR) (Drug)
Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Nicotine lozenge (NRT) (Drug)
Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Smartphone intervention with adherence components (COMBO-A) (Behavioral)
Varenicline + Lozenges + Smartphone Intervention with adherence components (VAR + NRT + COMBO-A)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention with medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Telephone Counseling (Behavioral)
Varenicline + Smartphone Intervention without adherence (VAR + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Varenicline (VAR) (Drug)
Varenicline + Smartphone Intervention without adherence (VAR + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Smartphone intervention without adherence components (COMBO-B) (Behavioral)
Varenicline + Smartphone Intervention without adherence (VAR + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing) and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Telephone Counseling (Behavioral)
Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Varenicline (VAR) (Drug)
Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Nicotine lozenge (NRT) (Drug)
Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Smartphone intervention without adherence components (COMBO-B) (Behavioral)
Varenicline + Lozenges + Smartphone Intervention without adherence (VAR + NRT + COMBO-B)
Participants will receive 13 weeks of varenicline (1 titration week + 12 weeks at full twice daily 1 mg dosing), 12 weeks of nicotine lozenges (2 mg or 4 mg), and a smartphone-based smoking cessation intervention without medication adherence components. All participants will receive up to 6 telephone counseling calls.
干预措施: Telephone Counseling (Behavioral)
结局指标
主要结局
Smoking Abstinence (26 weeks post-quit)
时间窗: 26 weeks after the scheduled quit day
Self-reported smoking abstinence over the past 7 days with breath CO≤6 ppm
Medication Adherence (weekly)
时间窗: Weekly starting on the quit day (for varenicline) or 1-week post-quit (for lozenges) through 12 weeks post-quit.
Adapted 7-item version of the Adherence to Refills and Medications Scale (ARMS). Separate scales will be administered to assess past-week varenicline and nicotine lozenge adherence. Scores may range from 7-28, with lower scores indicating better adherence.
次要结局
- Medication Adherence (weekly)(Weekly starting on the quit day (for varenicline) or 1-week post-quit (for lozenges) through 12 weeks post-quit.)
- Medication Adherence (daily)(Assessments begin 1 week before the quit day (varenicline) or on the quit day (lozenges) through 12 weeks post-quit.)
- Medication Adherence (weekly)(Weekly starting on the quit day (for varenicline) or 1-week post-quit (for lozenges) through 12 weeks post-quit.)
- Medication Adherence (daily)(Assessments begin 1 week before the quit day (varenicline) or on the quit day (lozenges) through 12 weeks post-quit.)
- Smoking Abstinence (12 weeks post-quit)(12 weeks after the scheduled quit day)