Clinical trial NCT02460900
Conditions: Smoking HIV
Sponsor: University of Maryland, Baltimore
Start date: 2016-07-01; Completion date: 2021-04-01
Enrollment: 184 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
The single greatest health behavior change that could improve cardiovascular morbidity and associated mortality is to assist people living with HIV/AIDS who smoke to quit. The investigators will use a factorial design to evaluate the most promising behavioral and pharmacologic treatments aimed at achieving maximal efficacy for smoking cessation among people living with HIV/AIDS who smoke. Results of this study will provide crucial, real world evidence of the best way for healthcare providers to help smokers living with HIV/AIDS quit smoking.

Detailed description:
The study used a factorial design to randomize participants into 4 conditions: (1) Varenicline (12 weeks) + Positively Smoke Free (PSF) (8 weeks); (2) Varenicline (12 weeks) + Standard of Care (brief advice to quit); (3) Placebo (12 weeks) + Positively Smoke Free (8 weeks); and (4) Placebo (12 weeks) + Standard of Care. The primary outcome was the 7-day point prevalence abstinence (PPA) (\<10mm) at 36 weeks.

The specific aims of our proposal are:

Primary Aim 1: Compare varenicline to placebo on rates of 7-day point prevalence abstinence (PPA) at 36 weeks in smokers with HIV/AIDS. We hypothesize that rates of smoking abstinence at week 36 will be higher in those treated with varenicline compared to placebo.

Primary Aim 2: Compare Positively Smoke Free to low intensity, brief counseling on rates of 7-day PPA at 36 weeks in smokers with HIV/AIDS. We hypothesize that rates of smoking abstinence at week 36 will be higher in those treated with Positively Smoke Free compared to brief counseling.

Primary Aim 3: Compare Positively Smoke Free + varenicline to the other two study conditions outlined above on rates of 7-day PPA in smokers with HIV/AIDS at 36 weeks. We hypothesize the effect of PSF with varenicline is greater than the effect of PSF or varenicline alone.

Exporatory Aim: Explore the effect of successful cessation/smoking abstinence on levels of cardiac specific biomarkers, nicotine biomarkers, generalized markers of inflammation, lipids, coagulation and monocyte/macrophage activation.

Arms: arm 1: Participants will receive varenicline and standard of care arm 2: Participants will receive placebo and standard of care arm 3: Participant will receive Positively Smoke Free (a tailored behavioral intervention) and Placebo arm 4: Participant will receive Positively Smoke Free (a tailored behavioral intervention) and Varenicline
Interventions: intervention 1: Varenicline intervention 2: Positively Smoke Free intervention 3: Placebo intervention 4: Standard of Care
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_SAP_000.pdf: 
Optimizing Smoking Cessation for People With HIV/AIDS Who Smoke; NCT02460900; June 1, 2016 
 
Methods (Study Design, Data Sources/Collection, Interventions, Measures, Limitations). 
Study Design  
The study used a factorial design to randomize participants into 4 conditions: (1) Varenicline (12 weeks) + 
Positively Smoke Free (8 weeks); (2) Varenicline (12 weeks) + Standard of Care (brief advice to quit); (3) 
Placebo (12 weeks) + Positively Smoke Free (8 weeks); and (4) Placebo (12 weeks) + Standard of Care. The 
factorial design is highly efficient method of assessing the efficacy of multiple treatments in a single trial as 
well as evaluating additive effects. The primary outcome was the 7-day point prevalence abstinence (PPA) 
(<10mm) at 36 weeks. The trial was IRB approved and registered with ClinicalTrials.gov (NCT02460900). The 
study was conducted from June 2016 to November 2020. 
Participants 
The study recruitment occurred at an urban HIV clinic. Eligibility screening occurred in person. Inclusion 
criteria were: (1) chart diagnosis of HIV; (2) current self-report of smoking >10 cigarettes per day or a score of 
> 5 of expired carbon monoxide (CO) as measured by Covita micro smokrlyzer;(3) motivation to quit smoking 
within the next 6 months (score 6-8 on the Abrams and Briener Readiness to Quit Ladder), (4) and not meeting 
criteria for moderate or severe DSM 5 substance use disorder as established by the  Mini International 
Neuropsychiatric Interview (MINI). Exclusion criteria were: (1) recent use of varenicline (past 3 months); (2) 
previous allergic reaction or hypersensitivity to varenicline; (3) current or planned pregnancy or nursing; (4) 
moderate to severe renal impairment; (5) unstable cardiovascular disease; (6) meeting criteria for possible 
dementia by scoring below 10 on the Hopkins HIV Dementia Scale; (7) current use of medication that would 
interfere with the protocol in the opinion of the Medically Accountable Physician including use of bupropion 
targeting nicotine dependence or (8) not medically stable enough to participate in the study based on the opinion 
of the Medically Accountable Physician. 
Randomization and Masking 
Study participants meeting eligibility criteria were randomized 1:1:1:1 to one of the four study conditions using 
permuted blocks, randomly varying in size.  Each randomization consisted of two components, the drug 
(placebo vs Varenicline) and the behavioral intervention (PSF vs SOC) allocation. Participants and study 
personnel were masked to allocation of medication (i.e., varenicline versus placebo); however, because of the 
nature of psychological interventions, the intervention team and participants were not masked to the treatment 
condition. Participants randomized to PSF were asked not to reveal their treatment condition to the study staff. 
Study personnel completing assessments were masked to all study conditions.  
Procedures 
During the eligibility visit, trained study personnel administered self-report questionnaires and documented 
laboratory results. The medically accountable study clinician completed a medical history, reviewed eligibility 
criteria including laboratory results, the results of a physical assessment (i.e., vital signs--blood pressure, heart 
and respiratory rates, height and weight) and confirmed study eligibility.  
Randomization 
Eligible participants were randomized (i.e., 1:1:1:1) to four study conditions: (1) Varenicline + PSF; (2) 
Varenicline + SOC; (3) Placebo + PSF; (4) Placebo + SOC using permuted blocks that randomly varied in size 
assuring both approximately equal sample sizes in each cell and minimizing the prediction of future allocations.  
Randomization consisted of two components, the drug (placebo vs Varenicline) allocation which is double blind 


Optimizing Smoking Cessation for People With HIV/AIDS Who Smoke; NCT02460900; June 1, 2016 
 
and the behavioral intervention (PSF vs SOC) allocation. For drug assignment, all raters, investigators, other 
staff and participants were blind to drug treatment assignment except for the dispensing pharmacist. Separate 
emergency unmasking envelopes for each participant were kept in a locked cabinet at the dispensing pharmacy 
in the case of a medical emergency. No medical emergencies occurred during the trial that required the 
dispensing pharmacist to be unmasked.  
Treatment allocation  
For those randomized to Varenicline, participants received 0.5 mg/day (days 1-3), then 0.5 mg twice per day 
(days 4-7). After the 7th day, participants received 1 mg twice per day for weeks 2-12 of the study. This is in 
accordance with package labeling. Placebo pills were identical in appearance and dosing regimen. Per 
recommendations by Varenicline package insert, the quit date was established as day 8. As a part of this 
investigator-initiated project, Pfizer provided Varenicline and matching placebo directly to the research 
pharmacy. 
For those randomized to Positively Smoke Free (PSF), participants received eight smoking cessation counseling 
sessions either in-person or by telephone by trained providers who received supervision by a study psychologist. 
PSF is an intensive, tailored, social cognitive theory-driven intervention that promotes cessation in PLWH 
smokers. The quit date was established as day 8 to be in accordance with the Varenicline quit date. Twenty-five 
percent of sessions were recorded and assessed by an independent reviewer completed a standardized checklist 
of topics covered. For those randomized to receive the standard of care condition, participants were given a quit 
smoking brochure and brief advice to quit (i.e. < five minutes) administered by a trained study staff.  
Outcome Assessment  
Trained research personnel assessed smoking behavior at baseline (week 0) and weeks 1, 2, 4, 8, 12, and 36. At 
baseline, current smoking and quitting history was assessed with questions drawn from the NHANES III. At all 
other time-points, trained research personnel assessed 7-day point-prevalence abstinence based on no self-
reported tobacco use (not even a puff) during the 7 days preceding the assessment and a CO ≤10ppm as 
measured by Covita micro smokrlyzer. 
Trained study personnel also collected participant’s response to a variety of questionnaires specifically chosen 
to evaluate mediators of Varenicline’s impact on smoking as well as PSF’s impact on smoking. These 
assessments occurred at baseline, 12 and 36 weeks. Mediators associated with Varenicline impact on smoking 
included Tobacco Craving, Smoking Temptation Scale Questionnaire (TCQ-SF) and Shiffman/Jarvik 
Withdrawal Questionnaire (SWQ). Mediators associated with PSF impact on smoking included the UCLA 
Loneliness Scale, Stages of Change Algorithm, the Abstinence Self-Efficacy Scale, Smoking Decisional 
Balance Questionnaire , Center for Epidemiologic Studies Depression Scale, and the Addictions Severity Index 
Lite. 
Pill and counseling adherence were assessed at Weeks 0, 1, 2, 4, 8, and 12. Pill adherence was tracked by the 
following question at each study visit: How many days in the last week did you take at least one of your study 
pills.  Pill adherence was defined by participant self-report of taking 6 or 7 pills at week 8 which coincided with 
their last receipt of varenicline or placebo. Counseling adherence was tracked by the percent of participant 
attendance at study completion. The total number of sessions a participant could attend was 8.  
Safety Monitoring 
Safety assessments occurred at Weeks 0, 1, 2, 4, 8 and 12. Adverse events were monitored at each study contact 
and classified and graded using the Common Terminology Criteria for Adverse Events and Common Toxicity 


Optimizing Smoking Cessation for People With HIV/AIDS Who Smoke; NCT02460900; June 1, 2016 
 
Criteria provided by the National Cancer Institute. The study physicians were consulted to determine if an event 
was an adverse event (AE) and a serious adverse event (SAE) and what, if any, treatment or follow-up was 
required. Separate emergency unblinding envelopes for each participant were kept in a locked cabinet at the 
dispensing pharmacy in the case of a medical emergency. A Data Safety Monitoring Board assessed all adverse 
events and serious adverse events.  
Power Calculation 
All power analyses were conducted with a two tailed alpha of .05 and power set to .80. With 184 participants, 
the study’s 2 main effects ((1) varenicline vs. placebo; (2) PSF versus Standard of Care were each powered to 
detect a Cohen’s h of .41 (medium effect) based on a quit rate of 6% for the control condition.  
Analysis  
Primary Aims: We used separate logistic regression models (SAS, 9.4: Proc Logistic) at each post baseline time 
point (12 weeks, 36 weeks) to assess the main effects of varenicline vs. placebo and PSF vs. SOC on smoking 
cessation. To assess if the combination of varenicline and PSF is significantly more effective than either of the 
treatments alone, we created an indicator variable for these 3 conditions with the combined treatment as the 
reference. Participants who completed baseline assessment and were randomized to treatment arm but were lost 
to follow-up were considered not abstinent.