Purpose
Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia.
Methods
In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28.
Results
Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57–1.87];
p
= 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0–14) in the nicotine group and 0 (0–13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3–7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups.
Conclusion
In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00134-022-06721-1.
This study aimed to assess patient investigational medication knowledge and to identify factors associated with medication understanding by adult outpatients included in clinical trials. A cross-sectional prospectively designed survey was conducted on consecutive volunteers at 21 university teaching hospitals (in France) from February to December 2014. Investigational medication understanding was assessed at the time of the first dispensing using a structured interviewer-administered questionnaire based on information obtained from the literature that provided an 8-point score. Demographic and other baseline data were collected using structured interviews. Of the 236 participants, 139 (58.9%) of the respondents were male, and the median age was 54.9 years (range: 18–83 years). The mean understanding score was 6.24 and 72.5% of the patients had a score of 6 or higher. In univariate analysis, the medication understanding score was negatively correlated with age (r = -0.15, p = 0.0247) and positively correlated with the level of education (r = 0.25, p = 0.0002). In multivariate analysis, prognostic factors of a higher medication understanding score were: graduation from high school or a higher level of education; HIV infection; phase II/III/IV studies; mention of the drug on the prescription form, and the dispensing of a single investigational medication. Only a quarter of the adult outpatients included in clinical trials had a maximum possible investigational medication understanding score. Being old and having a low level of education were found to be important risk factors for inadequate medication understanding. This and other data suggest that sponsors should encourage initiatives aimed at improving investigational medication understanding in adults enrolled in clinical trials.
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