A Trial of Directly Observed and Long-term Varenicline

• ClinicalTrials.gov Identifier: NCT03365362
• Recruitment Status: Recruiting
• First Posted: December 7, 2017
• Last Update Posted: October 22, 2020
• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institutes of Health (NIH); Pfizer; National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Shadi Nahvi, Albert Einstein College of Medicine

Tracking Information

• First Submitted Date: November 28, 2017
• First Posted Date: December 7, 2017
• Last Update Posted Date: October 22, 2020
• Actual Study Start Date: October 25, 2018
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2017)

• Initial abstinence [ Time Frame: 24 weeks ]
  Period of ≥ 24 hour self-reported abstinence during the intervention period
• Time to lapse [ Time Frame: 24 weeks ]
  First day on which subjects smoke, even a puff, after a period of initial abstinence
• Time to relapse [ Time Frame: 24 weeks ]
  First day of seven consecutive days of self-reported smoking after a period of initial abstinence

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 6, 2017)

• Durability of tobacco abstinence [ Time Frame: week 28 ]
  CO-verified, 7-day point prevalence abstinence at week 28
• Durability of tobacco abstinence [ Time Frame: week 52 ]
  CO-verified, 7-day point prevalence abstinence at week 52
• Cigarettes smoked per day [ Time Frame: 24 weeks ]
  self reported number of cigarettes smoked per day
• Nicotine dependence [ Time Frame: 24 weeks ]
  Fagerstrom test of nicotine dependence
• Quality of life [ Time Frame: 24 weeks ]
  Medical Outcomes Study Short Form 12

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of Directly Observed and Long-term Varenicline
• Official Title: Achieving Smoking Cessation Milestones in Opioid Treatment Patients: a Randomized 2 x 2 Factorial Trial of Directly Observed and Long-term Varenicline
• Brief Summary: This 2 x 2 factorial, randomized, double-blind, placebo-controlled trial will test two interventions: directly observed medication therapy, and long-term therapy with varenicline among 450 smokers with opioid use disorder recruited from community-based, outpatient opioid treatment programs. The analytic strategy will evaluate the milestones in smoking cessation-achieving initial abstinence, preventing lapse and preventing relapse--necessary for long-term cessation, and evaluate theoretically-guided psychological and social factors and pharmacogenetic factors that influence these cessation processes.
• Detailed Description: Tobacco use and tobacco-related disease are highly prevalent among persons with opioid use disorders (OUD). Unfortunately, traditional evidence-based smoking cessation interventions have yielded low rates of tobacco abstinence in this group. The majority of trials evaluating smoking cessation treatment interventions among persons with OUD have relied on short-term interventions that do not account for the unique challenges faced by these smokers, specifically, establishing initial abstinence, adhering to evidence-based cessation treatments, and maintaining abstinence once active treatments cease. Long-term smoking cessation medication treatment approaches have shown promise in promoting cessation and decreasing relapse among individuals without OUD, however the applicability of extended medication approaches to smokers with OUD may be limited by poor adherence to smoking cessation medications. Though adherence to cessation medication is strongly associated with cessation success, adherence is especially challenging for persons with OUD. Opioid treatment program-based directly observed therapy (DOT) interventions improve clinical outcomes in HIV and TB, and pilot data suggest that DOT varenicline is associated with increased smoking cessation medication adherence and may increase smoking cessation rates. In this 2 x 2 factorial, randomized, double-blind, placebo-controlled trial, the investigators will test two interventions: directly observed medication therapy, and long-term therapy with varenicline. The analytic strategy will evaluate the milestones in smoking cessation-achieving initial abstinence, preventing lapse and preventing relapse--necessary for long-term cessation, and evaluate theoretically-guided psychological and social factors and pharmacogenetic factors that influence these cessation processes. The investigators will recruit 450 smokers with OUD from community-based, outpatient opioid treatment programs and test the following specific aims: (1) to test the efficacy of directly observed varenicline therapy compared to self-administered varenicline therapy on smoking cessation milestones, (2) to test the efficacy of long-term varenicline compared to short-term varenicline on smoking cessation milestones, and (3) to understand the mechanism of smoking cessation by examining the impact of theory-guided psychological and social factors and of pharmacogenetic factors on cessation milestones.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Tobacco Use Disorder
• Opioid-use Disorder

Intervention

• Drug: Long-Term Varenicline
  Varenicline tablet x 24 weeks
  Other Names:

  • varenicline
  • chantix
• Drug: Short-Term Varenicline
  varenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet
  Other Names:

  • varenicline
  • chantix
  • placebo
• Behavioral: Directly Observed Therapy
  Varenicline doses are administered by opioid treatment program nurses
• Behavioral: Self Administered Therapy
  Varenicline doses are self-administered

Study Arms

• Experimental: Long-Term Varenicline
  Participants will receive 24 weeks of varenicline at standard doses (0.5 mg/day for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1 mg twice daily)
  Intervention: Drug: Long-Term Varenicline
• Active Comparator: Short-Term Varenicline
  Participants will receive 12 weeks of varenicline at standard doses (0.5 mg/day for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1 mg twice daily), followed by matching placebo twice daily through week 24.
  Intervention: Drug: Short-Term Varenicline
• Experimental: Directly Observed Therapy
  Participants receiving directly observed therapy (DOT) will receive varenicline from opioid treatment program nurses at the same time as they receive methadone, as well as individually packaged take-home doses for self administration on evenings/weekends.
  Intervention: Behavioral: Directly Observed Therapy
• Active Comparator: Self Administered Therapy
  Patients receiving varenicline self administered therapy (SAT) will self-administer all varenicline doses.
  Intervention: Behavioral: Self Administered Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 6, 2017): 450
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2023
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1) age ≥18 years old; 2) English or Spanish speaking (i.e., be able to participate in study interviews in English or Spanish); 3) current cigarette smoking (smoked at least 100 cigarettes/lifetime, smoking ≥ 5 cigarettes/day); 4) interest in quitting tobacco smoking; 5) receiving methadone or buprenorphine in the DoSA clinic one to six times weekly; 6) enrollment in a DoSA opioid treatment program ≥ 3 months; 7) stable methadone or buprenorphine dose for two weeks; 8) agreement to use contraception for the duration of the trial (among women with reproductive potential); 9) willingness to participate in all study components; and 10) ability to provide informed consent.

Exclusion Criteria:

1) serious or unstable disease, specifically: decompensated cirrhosis (INR≥ 1.7, albumin <2.7 g/dl or physical exam evidence of decompensated cirrhosis); severe cardiovascular disease (MI, PTCA, unstable angina, CABG, and/or serious arrhythmia in the previous 6 months); severe asthma or chronic obstructive pulmonary disease (requiring supplemental oxygen or hospitalization in past 6 months); HIV/AIDS (AIDS-defining illness or hospitalization in past 6 months); 2) creatinine clearance <30 mL/min; 3) history of seizure disorder; 4) women who are pregnant, breastfeeding, or contemplating pregnancy; 5) current suicidal ideation; 6) history of suicide attempt in the past year; 7) psychiatric hospitalization in the past year; 8) current DSM V criteria for major depressive episode, current bipolar disorder, or current psychotic disorder; 9) current DSM V criteria for alcohol use disorder; or 10) use of varenicline in the past 30 days.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Shadi Nahvi, MD, MS; 718 920 5379; snahvi@montefiore.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03365362
• Other Study ID Numbers: 2016-6688; R01DA042813 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Our final dataset will include: survey and laboratory data, including demographic, medical, tobacco, and other substance use-related information about all clinical trial subjects. The final dataset will be stripped of all personal identifiers.
• Supporting Materials: Study Protocol
• Supporting Materials: Analytic Code
• Time Frame: After data collection and cleaning is complete.
• Access Criteria: We will share data with qualified investigators whose research protocols have been approved by their institutions' Institutional Review Boards. Data will be made available to potential users under a NIDA-approved data-sharing agreement that ensures that: (1) data is used only for research purposes and does not identify individual participants; (2) data is handled in a secure and confidential way; and (3) data is destroyed or returned after analyses are completed.

• Responsible Party: Shadi Nahvi, Albert Einstein College of Medicine
• Study Sponsor: Albert Einstein College of Medicine

Collaborators

• National Institutes of Health (NIH)
• Pfizer
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Shadi Nahvi, MD, MS; Albert Einstein College of Medicine

• PRS Account: Albert Einstein College of Medicine
• Verification Date: October 2020