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The purpose of this pilot randomized trial is to determine the feasibility of e-cigarettes and telephone counselling (compared to transdermal nicotine replacement and telephone counselling) as a harm-reduction tool that may lead to increased smoking cessation in the perioperative setting in smokers presenting for elective surgery at the San Francisco Veterans Affairs Medical Center. Secondary outcomes include acceptability of e-cigarettes over transdermal nicotine replacement, length-of-stay in the post-anesthesia care unit, hospital length-of-stay, postoperative complications within the first 30-days, and smoking status 8-weeks after randomization. This pilot study is designed to provide the preliminary data necessary to plan and fund a larger-scale randomized clinical trial that will assess the utility of e-cigarettes in achieving smoking cessation perioperatively. Our ultimate goal is to add to the limited existing data on the safety and efficacy of e-cigarette use in smoking cessation, specifically in the perioperative setting where the risks of continued smoking are great and the motivation to stop is high.
It is well-known that smokers suffer more complications and higher risk of mortality after surgery than non-smokers. Despite this knowledge, it is unclear what clinicians can do to minimize this risk. Surgery represents a 'teachable moment' that might encourage smokers to engage in permanent cessation. Several small trials have shown that smoking cessation interventions can increase smoking cessation and reduce postoperative complications, particularly wound-healing complications, which can have an absolute risk reduction of up to 25%. Smoking cessation initiated in the perioperative period can also promote long-term smoking cessation. Despite the benefits of comprehensive smoking cessation interventions including nicotine replacement therapy, current standard of care at the SFVAMC does not routinely include specific preoperative smoking cessation pharmacotherapy or counselling. Although there is an urgent need for more data, e-cigarettes have been proposed as an alternative to nicotine replacement therapy that are at least as effective for smoking cessation, and may be more acceptable to some patients.
The main hypothesis of this pilot study is that the use of e-cigarettes and telephone counselling, compared to telephone counselling and transdermal nicotine replacement, in the perioperative period results in increased smoking cessation on the day of surgery and at 8-weeks after randomization in smokers presenting for elective surgery. As secondary hypotheses, the study will also assess the acceptability of e-cigarettes versus nicotine patches, postoperative complications within the first 30-days, length-of-stay in the PACU and hospital length-of-stay. The investigators will examine the above hypotheses through the following aims:
" Aim 1) To determine how e-cigarettes plus counselling compare to transdermal nicotine replacement plus counselling for the achievement of smoking cessation, when introduced prior to elective surgery in veterans.
The investigators plan to carry-out a pilot randomized controlled trial with parallel design comparing e-cigarettes and telephone counselling with transdermal nicotine replacement and telephone counselling. Our primary outcome is smoking cessation on the day of surgery, as confirmed biochemically by exhaled carbon monoxide. Smoking reduction (self-reported cigarettes per day) of 50% or more and bedside spirometry readings will be assessed as secondary outcomes.
" Aim 2) To determine the acceptability of e-cigarettes amongst veterans as an aid for smoking cessation and to determine the feasibility of recruitment, randomization, and follow-up procedures in preparation for large-scale trial.
Through implementation of this pilot trial, the investigators will determine the feasibility and acceptability of e-cigarettes for smoking cessation perioperatively in the veteran population and obtain the preliminary data necessary to run a larger trial on the effectiveness of e-cigarettes as a perioperative smoking cessation aid.
" Aim 3) To determine the safety of e-cigarettes as a harm reduction strategy to achieve short-term perioperative smoking cessation.
The investigators plan to improve the overall knowledge of the safety of short-term e-cigarettes use through careful surveillance for adverse events and side effects.
" Aim 4) To determine if e-cigarette use preoperatively is associated with a lower risk of complications postoperatively.
The investigators plan to measure the following secondary outcomes: postoperative complications and mortality within the first 30 days, post-anesthesia care unit (PACU) length-of-stay, and hospital length-of-stay. This will help us understand if e-cigarettes have the potential to be used for harm-reduction perioperatively.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ENDD | Experimental | 6-week supply of disposable "NJOY" ENDDs (e-cigarettes)
Both groups will receive: i) referral to the California Smokers' Helpline, ii) brief advice lasting less than 2 minutes, iii) a brochure from the ASA about quitting smoking before surgery |
|
| NRT (NicoDerm CQ) | Active Comparator | A prescription for 6 weeks of transdermal nicotine replacement (on-formulary at the VA) in the following doses: For smokers of 10 cigarettes per day or more, a 3-week supply of 21 mg/d, 1-week supply of 14 mg/d, 1-week supply of 7 mg/d, and 1-week of 0mg/d. Smokers of <10 cigarettes per day, 3 weeks of 14 mg/d patches 2 weeks of 7 mg/d patches, and 1-week of 0mg/d. Both groups will receive: i) referral to the California Smokers' Helpline, ii) brief advice lasting less than 2 minutes, iii) a brochure from the ASA about quitting smoking before surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ENDD (NJOY) | Behavioral | As described above. |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Smoking Status on the Day of Surgery (48-hour Point-prevalence Abstinence), by Self-report and Confirmed With Exhaled Carbon Monoxide (CO) | Confirmed abstinent. Abstinence confirmed with exhaled carbon monoxoide <10ppm. Time Frame depends on date of preadmission clinic visit | day of surgery (expected average around 1-2 weeks after enrollment/randomization) |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Use of Product - Number Reporting Use Daily or Most Days | how often product (e-cigarette or patch) was used (everyday except while hospitalized, most days, a few times a week, once a week, less than once a week, not at all) Result reported is those that used the product daily or most days | 8-weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susan M Lee, MD, MAS | UCSF / SFVAMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco VA Medical Center | San Francisco | California | 94121 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30280019 | Result | Lee SM, Tenney R, Wallace AW, Arjomandi M. E-cigarettes versus nicotine patches for perioperative smoking cessation: a pilot randomized trial. PeerJ. 2018 Sep 28;6:e5609. doi: 10.7717/peerj.5609. eCollection 2018. |
| Label | URL |
|---|---|
| Full peer-reviewed results | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nicotine Replacement Patch Group (Control) | Patients randomized to the NRT group received a 6-week supply of NicodermCQ patches (5 weeks) and placebo patches (1 week) appropriate to baseline nicotine consumption. |
| FG001 | Electronic Cigarette (END) Group | Those allocated to the END group received a 6-week supply of NJOY e-cigarettes (Scottsdale, AZ, USA) and were instructed to use the Bold (4.5%) e-cigarettes ad libitum for 3 weeks, the Gold (2.4%) e-cigarettes ad libitum for 2 weeks and the Study (0%) ecigarettes ad libitum for the final week. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Nicotine Replacement Therapy (NRT) | As described above |
| BG001 | Electronic Cigarette (END) | As described above |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Smoking Status on the Day of Surgery (48-hour Point-prevalence Abstinence), by Self-report and Confirmed With Exhaled Carbon Monoxide (CO) | Confirmed abstinent. Abstinence confirmed with exhaled carbon monoxoide <10ppm. Time Frame depends on date of preadmission clinic visit | Posted | Count of Participants | Participants | day of surgery (expected average around 1-2 weeks after enrollment/randomization) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nicotine Replacement Therapy (NRT) | As above | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Susan Ming Lee | Royal Columbian Hospital / University of British Columbia | 604-520-4253 | susanlee.anesthesia@gmail.com |
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| ID | Term |
|---|---|
| D012907 | Smoking |
| D014029 | Tobacco Use Disorder |
| D000072137 | Vaping |
| D016540 | Smoking Cessation |
| ID | Term |
|---|---|
| D001519 | Behavior |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000095488 | Nicotine Replacement Therapy |
| D009538 | Nicotine |
| D061485 | Tobacco Use Cessation Devices |
| D003419 | Crisis Intervention |
| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
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| NRT (NicoDerm CQ) | Drug | As described above. |
|
|
| telephone counseling | Behavioral | Referral to the California Smokers' Helpline. California Smokers' Helpline will call the patient 4 times, or as agreed upon by the patient. |
|
| brief advice | Behavioral | Brief advice lasting less than 2 minutes will be delivered by the research assistant, investigator, or healthcare provider. The advice will be similar to the following statement (customized as needed to the patient): "The most important advice I can give you is that quitting smoking is the number one thing you can do for your health and to prepare yourself for surgery. Quitting smoking before surgery may improve your chances of healing quickly. There's evidence that the longer you quit before your surgery, the fewer complications you'll have. I encourage you to make use of the resources that have been provided to you to help you quit and set your quit date for as soon as possible." |
|
| brochure | Behavioral | A brochure from the ASA (American Society of Anesthesiologists) about quitting smoking before surgery. Available free from the ASA: http://ecommerce.asahq.org/publicationsAndServices/PatientBrochure\_%20For%20Posting.pdf |
|
| Report of How Helpful the Product Was for Quitting |
7-point likert scale (strongly disagree to strongly agree)
|
| 8-weeks |
| How Satisfied the Patient Was With the Product (E-cigarette or Patch) | 7-point likert scale (strongly disagree to strongly agree)
| 8-weeks |
| How Likely the Patient Would be to Recommend the Product (E-cigarette or Patch) to Others | 7-point likert scale (strongly disagree to strongly agree)
| 8-weeks |
| Smoking Status 8-weeks After Randomization (Confirmed by Exhaled CO) | by self-report and confirmed by exhaled CO<10ppm - confirmed abstinent | 8-weeks |
| Smoking Reduction | 50% or less regular cigarette use compared to baseline as determined by asking participants to self-report daily cigarette use in cigarettes per day at each time point. | on day of surgery and 8-weeks after randomization |
| Number of Participants With Dual Use | use of both regular and e-cigarettes concurrently | on day of surgery and 8-weeks after randomization |
| Spirometry - FEV1/FVC Change | Change in FEV1/FVC from baseline to day of surgery / 8-weeks. FEV1/FVC is expressed in percent. For example, if FEV1/FVC was 75%, 80%, and 85% at baseline, day of surgery and 8-weeks, result is reported as change in FEV1/FVC being +5% and +10% for day of surgery and 8-weeks respectively. | day of surgery and 8-weeks |
| Spirometry - FEV1 | change in FEV1 (mL) compared to baseline | day of surgery and 8-weeks |
| Cotinine Level (Change in) | salivary | day of surgery and 8-weeks |
| Number of Participants With Postoperative Complications (Composite) | by chart review - research assistant or investigator examined notes and investigations postoperatively for complications by telephone self-report - patients were asked open-ended question about whether they experienced any postoperative complications | 30-days postop |
| Long-term Smoking Status - Use of Conventional Cigarettes | by self-report (7-day point prevalence) | 6 months |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | all patients will be asked about adverse events each time they are contacted (day of surgery, 30-days postoperatively, and 8-weeks after randomization), and they will also be able to call to report adverse events to the study team any time during the study. | 8 weeks |
| Number of Participants Postoperative Complications (Composite) | by telephone self-report | 30-days postop |
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Day seen prior to surgery | Mean | Standard Deviation | days |
|
| Diabetes | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Heart disease | Count of Participants | Participants |
|
| COPD | Count of Participants | Participants |
|
| Cigarettes smoked per day | Mean | Standard Deviation | cigarettes |
|
| Number of years smoking | Mean | Standard Deviation | years |
|
| Fagerstrom score | Fagerstrom is a validated scale for nicotine dependence. Higher score indicates more dependence. (min 1 max 10) 1-2 = low, 3-4 = low/mod, 5-7 = moderate, 8+ = high dependence | Mean | Standard Deviation | units on a scale out of 10 min 1 max 10 |
|
| Salivary cotinine (ng/ml) | Mean | Standard Deviation | ng/ml |
|
| Exhaled CO (ppm) | Mean | Standard Deviation | ppm |
|
| FEV1 (L) | Mean | Standard Deviation | L |
|
| FVC (L) | Mean | Standard Deviation | L |
|
| FEV1/FVC (%) | Mean | Standard Deviation | percent |
|
| Units | Counts |
|---|
| Participants |
|
|
| Secondary | Frequency of Use of Product - Number Reporting Use Daily or Most Days | how often product (e-cigarette or patch) was used (everyday except while hospitalized, most days, a few times a week, once a week, less than once a week, not at all) Result reported is those that used the product daily or most days | in-person visit at 8-weeks, or make-up phone call if unavailable in-person | Posted | Count of Participants | Participants | 8-weeks |
|
|
|
| Secondary | Report of How Helpful the Product Was for Quitting | 7-point likert scale (strongly disagree to strongly agree)
| Posted | Median | Inter-Quartile Range | units on a scale out of 7 | 8-weeks |
|
|
|
| Secondary | How Satisfied the Patient Was With the Product (E-cigarette or Patch) | 7-point likert scale (strongly disagree to strongly agree)
| Posted | Median | Inter-Quartile Range | units on a scale out of 7 | 8-weeks |
|
|
|
| Secondary | How Likely the Patient Would be to Recommend the Product (E-cigarette or Patch) to Others | 7-point likert scale (strongly disagree to strongly agree)
| Posted | Median | Inter-Quartile Range | units on a scale out of 7 | 8-weeks |
|
|
|
| Secondary | Smoking Status 8-weeks After Randomization (Confirmed by Exhaled CO) | by self-report and confirmed by exhaled CO<10ppm - confirmed abstinent | Those lost to follow-up assumed to still be smoking (1 in NRT group). Those who had telephone interview were unable to have exhaled CO verification (n=1 in NRT group, n=2 in END group). Since they were not verified by exhaled CO, they were not considered abstinent. | Posted | Count of Participants | Participants | 8-weeks |
|
|
|
| Secondary | Smoking Reduction | 50% or less regular cigarette use compared to baseline as determined by asking participants to self-report daily cigarette use in cigarettes per day at each time point. | Posted | Count of Participants | Participants | on day of surgery and 8-weeks after randomization |
|
|
|
| Secondary | Number of Participants With Dual Use | use of both regular and e-cigarettes concurrently | Posted | Count of Participants | Participants | on day of surgery and 8-weeks after randomization |
|
|
|
| Secondary | Spirometry - FEV1/FVC Change | Change in FEV1/FVC from baseline to day of surgery / 8-weeks. FEV1/FVC is expressed in percent. For example, if FEV1/FVC was 75%, 80%, and 85% at baseline, day of surgery and 8-weeks, result is reported as change in FEV1/FVC being +5% and +10% for day of surgery and 8-weeks respectively. | Posted | Mean | Standard Deviation | percent (change from baseline) | day of surgery and 8-weeks |
|
|
|
| Secondary | Spirometry - FEV1 | change in FEV1 (mL) compared to baseline | Posted | Mean | Standard Deviation | mL | day of surgery and 8-weeks |
|
|
|
| Secondary | Cotinine Level (Change in) | salivary | Posted | Mean | Standard Deviation | ng/ml | day of surgery and 8-weeks |
|
|
|
| Secondary | Number of Participants With Postoperative Complications (Composite) | by chart review - research assistant or investigator examined notes and investigations postoperatively for complications by telephone self-report - patients were asked open-ended question about whether they experienced any postoperative complications | Posted | Count of Participants | Participants | 30-days postop |
|
|
|
| Secondary | Long-term Smoking Status - Use of Conventional Cigarettes | by self-report (7-day point prevalence) | those lost assumed to still be smoking | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | all patients will be asked about adverse events each time they are contacted (day of surgery, 30-days postoperatively, and 8-weeks after randomization), and they will also be able to call to report adverse events to the study team any time during the study. | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
| Secondary | Number of Participants Postoperative Complications (Composite) | by telephone self-report | Posted | Count of Participants | Participants | 30-days postop |
|
|
|
| 10 |
| 0 |
| 10 |
| 6 |
| 10 |
| EG001 | Electronic Cigarette (END) | As above | 0 | 20 | 0 | 20 | 10 | 20 |
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Dry cough (persistent) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dry cough (intermittent) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| palpitations | Cardiac disorders | Systematic Assessment |
|
| throat irritation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| skin irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| other | General disorders | Systematic Assessment | includes (for NRT group) irritable mood, patch not sticking properly, increased cravings, jitteriness, diarrhea, dry mouth, anxiety, sleepiness and (for END group) wheezing, productive cough, choking sense, poor appetite, burning sensation, lip burn |
|
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| D015438 |
| Health Behavior |
| D006571 |
| Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |