Combination Nicotine Metered Dose Inhaler and Nicotine Patch for Smoking Cessation: A Randomized Controlled Trial.

INTRODUCTION: In order to replicate the rewarding effects of smoking, nicotine replacement therapies must deliver nicotine via the pulmonary route. We aimed to measure the efficacy of a simple pressurized metered dose inhaler containing nicotine combined with a nicotine patch for smoking cessation. METHODS: Double-blind randomized placebo-controlled, parallel group trial conducted at the University of Otago, Wellington, New Zealand. Five-hundred two adults (≥18 years) who smoked at least nine cigarettes per day, with a Fagerström Test for Nicotine Dependence ≥3 who wanted to quit, were randomized (1:1). INTERVENTIONS: active nicotine pressurized metered dose inhaler (pMDI) plus active nicotine patch, versus placebo pMDI plus active nicotine patch. Subjects were instructed to use the aerosols for 6 months when they felt an urge to smoke and the patches daily for 5 months, reduce their smoking and quit by the end of the fourth week. Subjects were followed for 7 months. The primary outcome was prolonged 6 month not smoked on 7 consecutive days, analyzed by intention-to-treat. RESULTS: For the primary outcome, 78/246 (31.71%) in the active group versus 46/256 (17.97%) in the control group were abstinent (odds ratio 2.12, 95% confidence interval 1.40 to 3.23). Adverse events were reported by 245/246 (99.6%) and 247/256 (96.5%) subjects in the active and control groups, respectively. Mild coughing which decreased with regular use was common with the nicotine aerosols. CONCLUSION: Inhaled nicotine from a metered dose inhaler combined with a nicotine patch substantially improves abstinence for 6 months amongst adult nicotine dependant smokers wanting to quit. IMPLICATIONS: In 2012, we published a systematic review of the use nicotine by inhalation in this journal. At that time we were unable to find any studies that had measured the effects of nicotine delivery by pMDI on smoking cessation, and we are not aware of any since 2012. Our study is the first to look at nicotine by pMDI in smoking cessation. The present trial demonstrates that a simple nonproprietary nicotine inhaler, using relatively inexpensive standard technology, increases smoking cessation rates over and above nicotine patch therapy, and could usefully enhance nicotine replacement in smoking cessation treatment.

Combination rapid-acting nicotine mouth spray and nicotine patch therapy in smoking cessation.

INTRODUCTION: Improved smoking cessation rates are urgently required if New Zealand is to reach its target of a smokefree nation by 2025, during which some 600,000 smokers will need to quit. Nicotine replacement therapy remains a core part of the pharmacological approach to smoking cessation. Oral nicotine solutions with rapid onset have recently become available. We have examined the effect of a nicotine spray and a nicotine patch on smoking cessation for 12 months. METHODS: We enrolled potential participants-smokers wanting to quit aged 18-70 years, who smoked ≥9 cigarettes per day-with Fagerström Test of Nicotine Dependence score ≥3 in a double-blind trial in 3 trial sites. Smokers were randomized to a nicotine or placebo spray for 6 months, and all received nicotine patches daily for 5 months. They were followed at regular intervals for 12 months. RESULTS: A total of 1,423 subjects were randomized to nicotine oral spray (1mg of nicotine free base per spray) plus nicotine patch or a placebo spray and nicotine patch. The nicotine mouth spray plus nicotine patch showed significant improvements in prolonged abstinence for all measures to 6 months (7 consecutive days at each visit for 6 months: 15.5% vs. 10.6%; p = .006) for the combination versus placebo and nicotine patch. Thereafter, the differences were not significant. CONCLUSIONS: The addition of a nicotine mouth spray to a nicotine replacement patch in a population of smokers receiving a low level of behavioral support improved early quitting, but the effects were not sustained.