Tobacco Use Cessation
Conditions
Brief summary
Many people living with HIV (PLWH) smoke. Smoking in these individuals is often undertreated. This study plans to assess the ability of various clinical pathways involving tobacco treatment medications and contingency management (paying smokers for not smoking) to improve smoking cessation in a group of PLWH.
Detailed description
Using a Sequential Multiple Assignment Randomized Trial (SMART) design, this project is a two-arm, two-stage randomized trial of 320 adult PWH who smoke cigarettes and receive care in one of three health systems (targeted enrollment changed from 632 to 320 with NCI approval and IRB protocol amendment). At inception, participants will be randomized to either combination nicotine replacement therapy (NRT, patch + short-acting NRT) or combination NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed by exhaled carbon monoxide \[eCO\] or collateral verification) in both arms will receive 12 more weeks of the same treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with medication switch to oral medication, varenicline or bupropion, or intensified level of CM (start CM if no CM during first 12 weeks, or CM with higher reward schedule \[CM plus\] if NRT+CM group initially). The intervention will be delivered by trained clinical pharmacists. The primary outcomes will be self-reported reduction in average cigarettes smoked per day at 24 weeks and 12 weeks (primary outcome changed from eCO-confirmed abstinence to self-reported abstinence with NCI approval and IRB protocol amendment). The specific aims of the proposed study are to: (1) identify the optimal adaptive approach to promote reduced tobacco use (changed from eCO-confirmed smoking abstinence with NCI approval and protocol amendment) (2) study the effectiveness of various adaptive strategies on CD4 count, HIV viral suppression, and VACS index (validated measure of morbidity and mortality risk); and (3) grounded in implementation science and using aHybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation.
Interventions
DRUGNicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler
Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.
DRUGVarenicline or bupropion
Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).
BEHAVIORALContingency Management
Participants will be financially rewarded for abstinence to tobacco.
Sponsors
National Cancer Institute (NCI)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential multiple assignment randomized trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV positive; * \>= 18 years old * Receiving HIV care at Yale-New Haven Hospital, Bridgeport Hospital, Mount Sinai Hospital, or SUNY Downstate STAR clinic; * Have smoked \>= 100 cigarettes in lifetime; * Currently smokes some days or every day; * Smokes, on average, \>= 5 cigarettes per day; * Able to provide written informed consent.
Exclusion criteria
* Using only non-cigarette nicotine products (i.e., e-cigs, Juul, etc.); * Currently using NRT, VAR, or bupropion (defined as use in the prior 7 days); * Self-report or urine testing confirming pregnancy, nursing, or trying to conceive; * Life-threatening or unstable medical, surgical, or psychiatric condition; * Inability to provide at least one collateral contact (family member or friend); * Living out of state; * Unable to read or understand English (except at Mount Sinai site).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self Reported Reduction in Average Cigarettes Smoked Per Day at 12 Weeks | Week 12 | Self reported reduction in average cigarettes smoked per day at 12 weeks |
| Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 24 weeks | Self reported reduction in cigarettes smoked per day at 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VACS Index 2.0 Score | 24 weeks from baseline | The Veterans Aging Cohort Study (VACS) 2.0 Index is A validated measure of morbidity and mortality. It estimates risk of 5-year all-cause mortality in patients with HIV. Total score range of 0-129. A higher total score indicates a greater risk of adverse health outcomes. |
| Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 12 Weeks | 12 weeks from baseline | Number of participants with smoking abstinence confirmed by exhaled carbon monoxide or next closest informant verification |
| HIV Viral Load, Detectable | 24 weeks from baseline | HIV viral load greater than 200 copies per milliliter of blood and detectable on standard lab test |
| CD4 Count | 24 weeks from baseline | CD4 lymphocyte cell count. Normal range is 500-1200 cells per cubic millimeter. As HIV infection progresses, CD4 count drops. |
| Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 24 weeks from baseline | Number of participants with smoking abstinence confirmed by exhaled carbon monoxide or next closest informant verification |
Countries
United States
Participant flow
Recruitment details
Participants were consented, completed baseline and randomized to one of 2 arms in Stage 1: nicotine replacement therapy (NRT) or NRT+ CM (contingency management). At week 12, participants who were abstinent remained in their original arm. Participants who were not abstinent were re-randomized. If NRT in Stage 1, re-randomized to NRT+CM or varenicline (VAR). If NRT+CM Stage 1, re-randomized to NRT+CM intensified or VAR+CM.
Participants by arm
| Arm | Count |
|---|---|
| Stage 1: Nicotine Replacement Only (NRT) Participants met with a clinical pharmacist 6 times (baseline visit plus 5 follow-up visits) for nicotine replacement therapy prescriptions and tobacco cessation counseling | 163 |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) Participants met with a clinical pharmacist 6 times (baseline visit plus 5 follow-up visits) for nicotine replacement (NRT) prescriptions and tobacco cessation counseling. Participants in the NRT+CM arm also had the opportunity to earn prizes (gift cards) for tobacco abstinence, verified by exhaled carbon monoxide or next closest informant verification. | 160 |
| Total | 323 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Stage 1 | Death | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 2 | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Stage 2 | Lost to Follow-up | 0 | 0 | 0 | 11 | 17 | 4 | 21 | 14 |
Baseline characteristics
| Characteristic | Stage 1: Nicotine Replacement Only (NRT) | Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | Total |
|---|---|---|---|
| Age, Continuous | 55.71 years STANDARD_DEVIATION 10.8 | 54.42 years STANDARD_DEVIATION 10.6 | 55.08 years STANDARD_DEVIATION 10.71 |
| CD4 cell count | 600.0 cells per cubic millimeter | 596.5 cells per cubic millimeter | 596.5 cells per cubic millimeter |
| Cigarettes per day | 10.0 cigarettes per day | 10.0 cigarettes per day | 10.0 cigarettes per day |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 42 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 130 Participants | 118 Participants | 248 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Exhaled carbon monoxide at baseline | 10.0 parts per million (ppm) | 10.0 parts per million (ppm) | 10.0 parts per million (ppm) |
| HIV viral load, detectable Viral load detectable | 19 Participants | 17 Participants | 36 Participants |
| HIV viral load, detectable Viral load not detectable | 143 Participants | 141 Participants | 284 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 116 Participants | 114 Participants | 230 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 29 Participants | 33 Participants | 62 Participants |
| Region of Enrollment United States | 163 Participants | 160 Participants | 323 Participants |
| Sex: Female, Male Female | 71 Participants | 71 Participants | 142 Participants |
| Sex: Female, Male Male | 92 Participants | 89 Participants | 181 Participants |
| VACS 2.0 score | 45.0 score on a scale | 42.0 score on a scale | 43.0 score on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 163 | 2 / 160 | 0 / 16 | 0 / 70 | 1 / 74 | 0 / 36 | 0 / 60 | 0 / 62 |
| other Total, other adverse events | 6 / 163 | 14 / 160 | 0 / 16 | 2 / 70 | 0 / 74 | 1 / 36 | 3 / 60 | 2 / 62 |
| serious Total, serious adverse events | 13 / 163 | 9 / 160 | 1 / 16 | 5 / 70 | 4 / 74 | 1 / 36 | 3 / 60 | 3 / 62 |
Outcome results
Primary
Self Reported Reduction in Average Cigarettes Smoked Per Day at 12 Weeks
Self reported reduction in average cigarettes smoked per day at 12 weeks
Time frame: Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | Self Reported Reduction in Average Cigarettes Smoked Per Day at 12 Weeks | 5.2 cigarettes per day |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | Self Reported Reduction in Average Cigarettes Smoked Per Day at 12 Weeks | 4.9 cigarettes per day |
Primary
Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks
Self reported reduction in cigarettes smoked per day at 24 weeks
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 7.90 cigarettes per day |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 6.23 cigarettes per day |
| Stage 2: NRT+CM | Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 2.97 cigarettes per day |
| Stage 2: NRT+CM responders | Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 10.92 cigarettes per day |
| Stage 2: varenicline or bupropion + CM | Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 4.00 cigarettes per day |
| Stage 2: NRT+CM plus | Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks | 4.20 cigarettes per day |
Secondary
CD4 Count
CD4 lymphocyte cell count. Normal range is 500-1200 cells per cubic millimeter. As HIV infection progresses, CD4 count drops.
Time frame: 24 weeks from baseline
Population: Lab results were collected for all participants at Week 24 including those who did not complete the Week 24 assessment battery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | CD4 Count | 668.00 Cells per cubic millimeter | Standard Deviation 384.08 |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | CD4 Count | 576.53 Cells per cubic millimeter | Standard Deviation 347.76 |
| Stage 2: NRT+CM | CD4 Count | 648.38 Cells per cubic millimeter | Standard Deviation 423.08 |
| Stage 2: NRT+CM responders | CD4 Count | 640.57 Cells per cubic millimeter | Standard Deviation 370.12 |
| Stage 2: varenicline or bupropion + CM | CD4 Count | 724.92 Cells per cubic millimeter | Standard Deviation 521.86 |
| Stage 2: NRT+CM plus | CD4 Count | 696.97 Cells per cubic millimeter | Standard Deviation 421.36 |
Secondary
Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 12 Weeks
Number of participants with smoking abstinence confirmed by exhaled carbon monoxide or next closest informant verification
Time frame: 12 weeks from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 12 Weeks | 16 Participants |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 12 Weeks | 36 Participants |
Secondary
Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks
Number of participants with smoking abstinence confirmed by exhaled carbon monoxide or next closest informant verification
Time frame: 24 weeks from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 4 Participants |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 6 Participants |
| Stage 2: NRT+CM | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 7 Participants |
| Stage 2: NRT+CM responders | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 23 Participants |
| Stage 2: varenicline or bupropion + CM | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 3 Participants |
| Stage 2: NRT+CM plus | Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks | 8 Participants |
Secondary
HIV Viral Load, Detectable
HIV viral load greater than 200 copies per milliliter of blood and detectable on standard lab test
Time frame: 24 weeks from baseline
Population: Lab results were collected for all participants at Week 24 including those who did not complete the Week 24 assessment battery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | HIV Viral Load, Detectable | 0 Participants |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | HIV Viral Load, Detectable | 10 Participants |
| Stage 2: NRT+CM | HIV Viral Load, Detectable | 14 Participants |
| Stage 2: NRT+CM responders | HIV Viral Load, Detectable | 3 Participants |
| Stage 2: varenicline or bupropion + CM | HIV Viral Load, Detectable | 5 Participants |
| Stage 2: NRT+CM plus | HIV Viral Load, Detectable | 7 Participants |
Secondary
VACS Index 2.0 Score
The Veterans Aging Cohort Study (VACS) 2.0 Index is A validated measure of morbidity and mortality. It estimates risk of 5-year all-cause mortality in patients with HIV. Total score range of 0-129. A higher total score indicates a greater risk of adverse health outcomes.
Time frame: 24 weeks from baseline
Population: Lab results were collected for all participants at Week 24 including those who did not complete the Week 24 assessment battery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1: Nicotine Replacement only (NRT) | VACS Index 2.0 Score | 42.88 score on a scale | Standard Deviation 15.09 |
| Stage 1: Nicotine Replacement (NRT) + Contingency Management (CM) | VACS Index 2.0 Score | 47.26 score on a scale | Standard Deviation 17.61 |
| Stage 2: NRT+CM | VACS Index 2.0 Score | 49.42 score on a scale | Standard Deviation 19.61 |
| Stage 2: NRT+CM responders | VACS Index 2.0 Score | 42.65 score on a scale | Standard Deviation 15.38 |
| Stage 2: varenicline or bupropion + CM | VACS Index 2.0 Score | 42.66 score on a scale | Standard Deviation 15.66 |
| Stage 2: NRT+CM plus | VACS Index 2.0 Score | 43.63 score on a scale | Standard Deviation 15.7 |