Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Primary Care Clinical Sciences, University of Birmingham, Birmingham, UK.
Health Technol Assess. 2018 Aug;22(41):1-84. doi: 10.3310/hta22410.
Nicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data.
To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading.
Open-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis.
NHS smoking cessation clinics.
People seeking help to stop smoking.
Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators.
The primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model.
In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) -0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI -£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving.
The open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified.
Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication.
Current Controlled Trials ISRCTN33031001.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in ; Vol. 22, No. 41. See the NIHR Journals Library website for further project information.
尼古丁预加载是指在戒烟日期前使用尼古丁替代疗法（NRT）同时正常吸烟。其目的是降低吸烟的欲望，从而减少戒烟后对吸烟的渴望，这是早期复吸的主要原因。一项先前的系统评价显示，尼古丁预加载的有效性和作用机制证据不一致，且缺乏成本效益数据。
评估（1）在常规 NHS 环境中，与常规护理相比，尼古丁预加载在有效性、安全性和耐受性方面的情况，（2）预加载的作用机制，以及（3）预加载的成本效益。
开放标签随机对照试验，同时检查中介效应和成本效益分析。
NHS 戒烟诊所。
寻求帮助戒烟的人。
尼古丁预加载包括在戒烟日期前的 4 周内佩戴 21mg/24 小时尼古丁贴片。此外，还提供了最低限度的行为支持，以解释干预的基本原理并支持依从性。在对照组中，参与者接受了等效的行为支持。随机分组按中心分层，并对研究人员进行了隐藏。
主要结局是使用 Russell 标准评估的 6 个月长期戒烟。次要结局是 4 周和 12 个月的戒烟。从基线到戒烟后 1 周评估不良事件（AE）。在计划分析中，我们调整了使用伐尼克兰（Champix；辉瑞公司，纽约，NY，美国）作为戒烟后的药物。成本效益分析从卫生服务的角度出发。试验内分析比较了试验臂在 13 个月的试验入组期间与之前 6 个月的卫生服务成本。基础案例基于缺失成本数据的多重插补。我们使用欧洲烟草保护投资效用量化研究（EQUIPT）模型来模拟与吸烟相关的疾病的长期健康结果。
共有 1792 人符合条件并被纳入研究，其中 893 人被随机分配到对照组，899 人被随机分配到干预组。在干预组中，49 人（5.5%）提前停止预加载，大多数人每天都在使用。主要结局，即经生物化学验证的 6 个月戒烟率，在干预组中为 157 人（17.5%），对照组中为 129 人（14.4%），差异为 3.02 个百分点[95%置信区间（CI）-0.37 至 6.41 个百分点；优势比（OR）1.25，95%CI 0.97 至 1.62； = 0.081]。调整戒烟后使用伐尼克兰的情况后，OR 为 1.34（95%CI 1.03 至 1.73； = 0.028）。次要戒烟结局相似。严重不良事件（AE）发生率的 OR 为 1.12（95%CI 0.42 至 3.03）。与对照组相比，预加载组中出现中度至重度恶心的比例额外增加了 4%。有证据表明，减少吸烟的欲望和减少吸烟吸入可以介导预加载对戒烟的影响。与对照组相比，预加载组在 6 个月随访时的增量成本效益比为 710 英镑（95%CI-13674 至 23205 英镑），但在 12 个月和长期来看，预加载更具成本效益，80%的概率是节省成本。
开放性设计可能部分解释了中介结果。结局评估无法进行盲法，但进行了生物化学验证。
在试图戒烟前使用尼古丁贴片预加载 4 周可以增加成功戒烟的人数，但由于预加载后减少了伐尼克兰的使用，其益处受到了损害。如果能够克服这一影响，那么尼古丁预加载在长期来看可能会改善健康状况并降低卫生服务成本。未来的工作应确定如何确保使用尼古丁预加载的人选择使用伐尼克兰作为戒烟药物。
当前对照试验 ISRCTN33031001。
该项目由英国国家卫生与临床优化研究所（NIHR）健康技术评估计划资助，全文将在 ; Vol. 22, No. 41 中发布。有关该项目的更多信息，请访问 NIHR 期刊库网站。
