Use of Nicotine Replacement Therapy (NRT) Sample and Brief Smoking Cessation Advice for Recruiting Smokers

Study Overview
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Brief Summary
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Background More than 60% of the daily smokers in Hong Kong have never tried and have no intention to quit smoking. About 30.8% of daily smokers attempted to quit but failed. Nicotine replacement therapy (NRT) is a safe and effective pharmacotherapy to reduce withdrawal symptoms during early stage of tobacco abstinence and increase quit rate. However, the prevalence of using NRT in Hong Kong is lower than most of the developed countries. The proposed project aims to test if providing free NRT sampling to smokers can increase quit attempt, the use of smoking cessation (SC) services and abstinence. Methods University undergraduate students will be trained, and will invite smokers at outdoor smoking hotspots to quit smoking and enroll into SC services. Eligible smokers will be randomized to experimental or control group according to a cluster randomization, using recruitment session as the randomization unit. The experimental group will be provided with 1-week free NRT sampling and medication counselling, whereas the control group will be provided medication counselling. Both groups are advised to enroll in the SC services. The two primary outcomes include (1) the proportion of smokers who enroll in any SC service in Hong Kong within 1 month of the recruitment; and (2) the proportion of smokers who report quit attempts at 1 month follow-up Discussions The findings will inform the feasibility and effectiveness of delivering free NRT sampling to increase quit attempt, the use of smoking cessation services and abstinence. It will yield more information on smokers' adherence to the NRT sampling, side effect and safety issue of the usage.

Detailed Description
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Study design The proposed project has 4 phases: (1) Training of SC ambassadors (SCAs) for the SC promotion; (2) SC promotion sessions to deliver the medication counselling and NRT sampling (experimental group), or the advice to use NRT only (control group); (3) Follow-up of the recruited smokers; (4) Evaluation of the effectiveness of training, promotions, and use of NRT sampling. To examine the effectiveness of NRT sampling for recruitment and quitting, a multi-site cluster RCT (allocation ratio 2:1) will be used. All promotion sessions will be randomly allocated to either the experimental or the control group. The experimental group will receive medication counselling and NRT samples, while the control group only receive the advice to use NRT. Both groups are advised to enroll in any smoking cessation service in Hong Kong. Because smokers who receive NRT sampling will be more likely to participate in the study, the experimental sessions will then recruit more smokers than the control sessions. Hence, the allocation ratio of participants is arbitrarily set at 2:1. To increase comparability between the two groups, the promotion sessions of one hotspot will be randomly allocated to either group. All recruitment and quitting outcomes in the smokers between the experimental and control group will be compared. Subjects Smokers with the following inclusion criteria will be invited to participate in our RCT: (1) Hong Kong residents, (2) aged 18 to 65 years, (3) have used any tobacco products in the past month, (4) able to read and speak Chinese, (5) have not used NRT for the past month, (6) no severe angina, serious cardiac arrhythmias and hypertension, (7) have not suffered acute myocardial event in the past 4 weeks, (8) neither pregnant nor breastfeeding, (9) not under medication and treatment due to mental illness. To confirm the smoking status, in those who use conventional cigarettes, smokers' exhaled carbon monoxide will be measured on-site. Nurses will measure the blood pressure if smoker is aged over 50 years old, obese by observation, or upon patient requests. The inclusion criterion no. 3 was smoke 10 cigarettes or more per day in the past week and is amended to have used any tobacco products in the past month. The initial intention of setting the inclusion criteria of at least 10 cigarettes per day (CPD) is to recruit smokers who have moderate to strong level of craving and a greater need for NRT. However, we also recognize that one of the objectives of the research is to promote the use of NRT for quit attempts with NRT sampling. In fact, smokers who smoke less than 10 CPD can also benefit from using NRT gums. Therefore, the change in the inclusion criteria does not deviate from our research aim. In contrast, with the removal of the criterion for CPD, we will be able to reach out to a larger group of smoking population and encourage more smokers to use NRT to quit smoking. Procedures In the experimental sessions, the SCAs will approach and distribute souvenirs (e.g. a pen) or leaflets to the smokers at outdoor smoking hotspots for 3-4 hours. The souvenirs and leaflets will have SC messages, quitline number and other SC services. If a smoker is willing to accept them and talk to the SCAs, the SCAs will advise the smoker to quit using the AWARD protocol. The AWARD protocol includes (1) Ask the smoking history, (2) Warn about the high risk (i.e., half of the smokers will die of smoking-related diseases), (3) Advise to quit, (4) Refer to the SC clinics of TWGHs and (5) Repeat the above advice (Do-it-again) [4]. Our previous studies have shown that the AWARD protocol is a feasible and appropriate tool used by non-healthcare professionals to promote smoking cessation [4-6]. If the smoker is interested in smoking cessation, the SCAs will introduce NRT to the smoker and conduct a preliminary assessment of his/her eligibility for enrolling in the NRT sampling programme. The SCAs will invite him/her to go to the smoking cessation truck nearby to receive counselling by an onsite nurse. If the smoker is not eligible, he/she can still enroll in the cessation service provided by the SC clinics. The intervention and assessment will mostly be taken place in a smoking cessation truck when the recruitment venues allow us to park the truck nearby, or at outdoor areas when a parking space for a truck is not available. Intervention: NRT sampling and medication counselling In the experimental sessions, an onsite nurse will assess whether each participant is fit for using NRT with further assessment on his/her current physical status, medication and blood pressure. If the participant is willing to use NRT to quit smoking and pass the nurse's assessment, he/she will be prescribed the NRT sample, regardless of whether they use NRT for smoking reduction and when the quit day is. The nurse will help the participant decide which type of NRT product (gum: 2mg, patch: 14mg or 21mg) that he/she can use and advise him/her on how to use the NRT based on his/her smoking habit and daily cigarette consumption. In addition, the nurse will deliver medication counselling which addresses five main components: (1) the benefits for using NRT in quitting, (2) withdrawal symptoms due to smoking cessation, (3) side effects of NRT, (4) instructions for using NRT, and (5) making appointments for TWGHs SC clinics. An instruction card for using NRT will be given. Afterwards, the participant will receive 1-week free NRT. Our research staff will send the NRT sample via mail within 2 days. In the control sessions, all the above procedures for the experimental group will be applied, except that they will not receive an NRT sample and an instruction card about the use of NRT. Instead, they will be advised to obtain free NRT by enrolling in the SC clinics. Both groups will receive a one-page leaflet provided by the SC clinics, and encouraged to make service appointments with the SC clinics. The leaflet briefly introduced this RCT, the use of NRT and the service provided by the smoking cessation clinics. When the participant has finished the above procedures, the research assistant or trained ambassadors (under supervision of the research staff) or the nurse will introduce the trial of evaluating the effect of NRT sample and the outreach service and screen the eligibility of participating in the trial. If the participant is eligible, the research assistant will seek his/her consent to participate in the trial, and complete a baseline questionnaire. Some smokers are willing to participate in the RCT, but they have no time to receive all intervention or complete all recruitment procedures at the hotspots. In these cases, the SCAs will only briefly introduce the RCT, ask the participants to give written consent. A nurse will contact these participants to complete the baseline questionnaire and deliver the intervention (medication advice and NRT prescription) within the same day. If the participants are in the experimental group, after the telephone counselling by the nurse, our research staff will send the NRT sample via mail within 2 days. Randomization We will use cluster randomization based on promotion session as the cluster unit because the procedures of individual randomization are difficult in outdoor areas as found in our pilot RCT. The PI will randomly allocate the promotion sessions within a hotspot to the 2 groups by a list of group allocation which is based on a list of random numbers from Excel programme. Each hotspot will have 2 or more promotion sessions, and each session will last for about 3-4 hours. If a hotspot has 2 promotion sessions on 1 single day, the 2 sessions will be allocated into the same RCT group, and we will organize 2 more promotion sessions in this hotspot on another day. Allocation concealment All recruitment staff will know the group allocation before each promotion session, so no group concealment can be done. Blinding Participants, recruitment staff and nurses cannot and will not be blinded to the intervention. Assessors of the follow-up outcomes and the research analysts will not be involved in the recruitment and intervention delivery, and will be blinded to the group allocation (single blindness). Baseline assessments Baseline information includes socio-demographics, current use of conventional and new tobacco products, such as heat-not-burn tobacco products and electronic cigarettes, history of quit attempts, and intention to quit. Nicotine dependence will be assessed by the Fagerström Test for Nicotine Dependence.24 Participants will also be asked about their self-efficacy in quitting, based on the perceived importance, difficulty and confidence to quit smoking on a Likert scale from 0 to 10. Follow-up All the smokers who consent to the follow-up will be contacted via telephone or WhatsApp around one week by a nurse or a trained research staff after recruitment. The aim of this follow-up is (1) to enquire if there is any progress towards smoking cessation and (2) encourage the use of NRT for a quit attempt and/or enrollment in SC services as soon as possible. If participants show no interest to quit, the nurse/research staff will use the 5R approach to re-motivate the quitting intention. The 5R approach is being adopted by the local and international smoking cessation guideline including the discussion on why quitting is important (relevance), hazards of smoking (risk), benefits of quitting (rewards), difficulties (roadblocks) and repeated quit attempts (repetition). If participants report any contra-indication(s) to NRT, the nurse/research staff will discuss the reasons with them, and, if necessary, refer the participants to the physician in the smoking cessation clinic. At 1-, 3- and 6-month follow-up, the quitting outcomes will be assessed by a trained interviewer through telephone who is blinded to the subject's group status. A small amount (HK$50=US$6.4) of cash voucher will be offered to those who completed a follow-up survey. At 6-month follow-up, participants who reported no smoking in past 7 days will be invited for a biochemical validation of the abstinence. Participants with exhaled carbon monoxide 4ppm or below and saliva cotinine level below 10ng/ml will be considered as validated abstinence. Participants of the biochemical validation, no matter the abstinence status is confirmed, will be offered a HK$50 (US$6.4) cash voucher for the travel compensation. Sample size determination As we predicted that the recruitment sessions of providing free NRT samples will recruit more smokers, participant ratio of the 2 trial groups is arbitrarily set at 2:1. At the time we designed this trial, our preliminary analysis of the aforementioned pilot RCT showed that the rate of quit attempt in the intervention and control group was 26% and 12% at 3-month follow-up, respectively. We arbitrarily reduced these rates to 20% and 8% for 1-month follow-up. To detect a significant difference with normal test and a power of 95% and 5% significance level, we need 485 subjects in the RCT (allocation ratio 2:1; 323 vs 162). Based on the method of Eldridge et al. (2006),29 conservatively assuming that we could recruit 8 participants per session on average and the intra-cluster correlation coefficient was 0.1, the design effect is estimated to be 1.7. Thus, the minimum sample size required for the trial is 825 (=1.7 X 485) participants and 60 sessions in total. With the similar calculation, the required sample size for detecting a significant difference in the proportion of using any smoking cessation service is 421. Statistical analysis An independent data analyst will perform the data check of missing, duplication and validity on the completed dataset before analysis is done. All data will be de-identified in the data analysis. To assess the effect of NRT sampling to the process outcomes, the number of smokers who accept the brief advice or consent the RCT in each recruitment session will be the outcome variables of Poisson regression model, with group allocation as the predictor, and total number of approached smokers in that promotion session as the offset variable. Considering the possibility of correlated outcomes of participants within the recruitment session, an analysis by generalized estimating equations model, assigning session as a random effect, will be used to summarize the intervention effect on the primary outcome. The analysis adopted a longitudinal approach with an exchangeable structure for the correlation matrix of the outcome. Other secondary outcomes will be analyzed with either generalized estimating equations models (binary outcomes; e.g. tobacco abstinence) or linear mixed model (continuous outcomes; e.g. perceived importance to quit smoking). Both intention-to-treat (treating participants as smokers without quit attempts and no use of cessation services if they are lost to follow-up) and per protocol analysis will be done. Subgroup analysis of comparing the primary and secondary outcomes between participants receiving the nurse-led intervention onsite and those receiving the intervention via telephone will be done.

Official Title
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Use of Nicotine Replacement Therapy (NRT) Sample and Brief Smoking Cessation Advice for Recruiting Smokers to Smoking Cessation Services and Motivating Quit Attempts

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Nicotine replacement therapy (NRT) sampling
* Behavioral: Medication counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hong Kong residents aged 18 to 65 years have used any tobacco products in the past month able to read and speak Chinese have not used NRT for the past month Exclusion Criteria: Have severe angina, serious cardiac arrhythmias and hypertension Have suffered from acute myocardial event in the past 4 weeks Pregnant nor breastfeeding Under medication and treatment due to mental illness One of the inclusion criteria was smoke 10 cigarettes or more per day in the past week and is amended to have used any tobacco products in the past month. The initial intention of setting the inclusion criteria of at least 10 cigarettes per day (CPD) is to recruit smokers who have moderate to strong level of craving and a greater need for NRT. However, we also recognize that one of the objectives of the research is to promote the use of NRT for quit attempts with NRT sampling. In fact, smokers who smoke less than 10 CPD can also benefit from using NRT gums. Therefore, the change in the inclusion criteria does not deviate from our research aim. In contrast, with the removal of the criterion for CPD, we will be able to reach out to a larger group of smoking population and encourage more smokers to use NRT to quit smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The intervention group will receive nicotine replacement therapy (NRT) sampling and medication counseling. The nurse will help the subject to decide which NRT product (patch or gum) he/she can use and advise how to use the NRT based on his/her smoking habit and amount of cigarette consumption. In addition, the nurse will deliver medication counselling which addresses five main components: (1) the benefits for using NRT in quitting, (2) withdrawal symptoms due to smoking cessation, (3) side effects of NRT, (4) instructions for using NRT, and (5) making appointments for TWGHs SC clinics. Afterwards, the participant will receive 1-week free NRT, an education card about NRT and a one-page leaflet provided by the SC clinics. | Drug: Nicotine replacement therapy (NRT) sampling<br>* 1-week free NRT samples (patch or gum)<br>Behavioral: Medication counseling<br>* Medication counseling<br>|
| Active Comparator: Control<br>The control group subjects will receive medication counseling. They will be advised to obtain free NRT by enrolling in the smoking cessation services, but will not be given the sampling. The same one-page leaflet will be provided by the SC clinics. | Behavioral: Medication counseling<br>* Medication counseling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Enroll in Any Smoking Cessation Service in Hong Kong | Number of participants who enroll in any smoking cessation service in Hong Kong | 1 month | 
| Number of Participants With Self-reported Quit Attempt | No smoking for at least 24 hours in the past month | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Enroll in Any Smoking Cessation Service in Hong Kong | Number of participants who enroll in any smoking cessation service in Hong Kong | 3 months | 
| Number of Participants With Self-reported Quit Attempt | No smoking for at least 24 hours in the past month | 3 months | 
| Number of Participants With Self-reported Use of NRT in Past Week/Month | self-reported use of NRT in past week/month | 1 month | 
| Number of Participants With Self-reported Use of NRT in Past Week/Month | self-reported use of NRT in past week/month | 3 months | 
| Number of Participants With Self-reported Tobacco Abstinence in Past 7 Days | self-reported tobacco abstinence in past 7 days | 3 months | 
| Number of Participants With Self-reported Tobacco Abstinence in Past 30 Days | self-reported tobacco abstinence in past 30 days | 3 months | 
| Number of Participants With Self-reported Tobacco Abstinence in Past 7 Days | self-reported tobacco abstinence in past 7 days | 6 months | 
| Number of Participants With Self-reported Tobacco Abstinence in Past 30 Days | self-reported tobacco abstinence in past 30 days | 6 months | 
| Biochemically Validated Abstinence at 6-month Follow-up | measurement of exhaled carbon monoxide using a Smokerlyzer, and a saliva cotinine test | 6 months | 
| Perceived Importance, Difficulty and Confidence to Quit Smoking | Self-efficacy will be evaluated according to the importance of quitting on a scale of 0 to 10 (0, least important; 10, most important), the difficulty of quitting on a scale of 0 to 10 (0, least difficult; 10, most difficult), and confidence in quitting on a scale of 0 to 10 (0, least confident; 10, most confident). For the scale of measuring quitting importance and confidence, higher scores mean a better outcome and for the scale of measuring difficulty, higher scores mean a worse outcome. | 1 month | 
| Perceived Importance, Difficulty and Confidence to Quit Smoking | Self-efficacy will be evaluated according to the importance of quitting on a scale of 0 to 10 (0, least important; 10, most important), difficulty of quitting on a scale of 0 to 10 (0, least difficult; 10, most difficult), and confidence in quitting on a scale of 0 to 10 (0, least confident; 10, most confident) | 3 months | 
| Perceived Importance, Difficulty and Confidence to Quit Smoking | Self-efficacy will be evaluated according to the importance of quitting on a scale of 0 to 10 (0, least important; 10, most important), difficulty of quitting on a scale of 0 to 10 (0, least difficult; 10, most difficult), and confidence in quitting on a scale of 0 to 10 (0, least confident; 10, most confident) | 6 months | 
| Progression Towards Smoking Cessation | progression towards smoking cessation as measured by Incremental Behavior Change toward Smoking cessation (IBC-S). The minimum value is 3 and the maximum value is 27. Higher scores mean a better outcome. | 1 month | 
| Progression Towards Smoking Cessation | progression towards smoking cessation as measured by Incremental Behavior Change toward Smoking cessation (IBC-S). The minimum value is 3 and the maximum value is 27. Higher scores mean a better outcome. | 3 months | 
| Progression Towards Smoking Cessation | progression towards smoking cessation as measured by Incremental Behavior Change toward Smoking cessation (IBC-S). The minimum value is 3 and the maximum value is 27. Higher scores mean a better outcome. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intervention, nicotine replacement sample, smoking cessation, smoking hotspots