tetano
Editor, Senior Moderator
Intensive Care Med
. 2022 Jun 9.
doi: 10.1007/s00134-022-06721-1. Online ahead of print.
Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial
Guylaine Labro[SUP] 1 [/SUP], Florence Tubach[SUP] #[/SUP][SUP] 2 [/SUP], Lisa Belin[SUP] 2 [/SUP], Jean-Louis Dubost[SUP] 3 [/SUP], David Osman[SUP] 4 [/SUP], Grégoire Muller[SUP] 5 [/SUP], Jean-Pierre Quenot[SUP] 6 7 8 [/SUP], Daniel Da Silva[SUP] 9 [/SUP], Jonathan Zarka[SUP] 10 [/SUP], Matthieu Turpin[SUP] 11 [/SUP], Julien Mayaux[SUP] 12 [/SUP], Christian Lamer[SUP] 13 [/SUP], Denis Doyen[SUP] 14 [/SUP], Guillaume Chevrel[SUP] 15 [/SUP], Gaétan Plantefeve[SUP] 16 [/SUP], Sophie Demeret[SUP] 17 [/SUP], Gaël Piton[SUP] 18 [/SUP], Cyril Manzon[SUP] 19 [/SUP], Evelina Ochin[SUP] 20 [/SUP], Raphael Gaillard[SUP] 21 22 [/SUP], Bertrand Dautzenberg[SUP] 23 24 [/SUP], Mathieu Baldacini[SUP] 1 [/SUP], Said Lebbah[SUP] 2 [/SUP], Makoto Miyara[SUP] 25 [/SUP], Marc Pineton de Chambrun[SUP] 26 27 [/SUP], Zahir Amoura[SUP] #[/SUP][SUP] 21 [/SUP], Alain Combes[SUP] #[/SUP][SUP] 28 29 [/SUP], NICOVID-REA Trial Group
Collaborators, Affiliations
Abstract
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.
Keywords: Acute respiratory failure; Artificial; COVID-19; Intensive care units; Nicotine; Nicotinic receptor; Randomized trial; Ventilation.
. 2022 Jun 9.
doi: 10.1007/s00134-022-06721-1. Online ahead of print.
Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial
Guylaine Labro[SUP] 1 [/SUP], Florence Tubach[SUP] #[/SUP][SUP] 2 [/SUP], Lisa Belin[SUP] 2 [/SUP], Jean-Louis Dubost[SUP] 3 [/SUP], David Osman[SUP] 4 [/SUP], Grégoire Muller[SUP] 5 [/SUP], Jean-Pierre Quenot[SUP] 6 7 8 [/SUP], Daniel Da Silva[SUP] 9 [/SUP], Jonathan Zarka[SUP] 10 [/SUP], Matthieu Turpin[SUP] 11 [/SUP], Julien Mayaux[SUP] 12 [/SUP], Christian Lamer[SUP] 13 [/SUP], Denis Doyen[SUP] 14 [/SUP], Guillaume Chevrel[SUP] 15 [/SUP], Gaétan Plantefeve[SUP] 16 [/SUP], Sophie Demeret[SUP] 17 [/SUP], Gaël Piton[SUP] 18 [/SUP], Cyril Manzon[SUP] 19 [/SUP], Evelina Ochin[SUP] 20 [/SUP], Raphael Gaillard[SUP] 21 22 [/SUP], Bertrand Dautzenberg[SUP] 23 24 [/SUP], Mathieu Baldacini[SUP] 1 [/SUP], Said Lebbah[SUP] 2 [/SUP], Makoto Miyara[SUP] 25 [/SUP], Marc Pineton de Chambrun[SUP] 26 27 [/SUP], Zahir Amoura[SUP] #[/SUP][SUP] 21 [/SUP], Alain Combes[SUP] #[/SUP][SUP] 28 29 [/SUP], NICOVID-REA Trial Group
Collaborators, Affiliations
- PMID: 35676335
- DOI: 10.1007/s00134-022-06721-1
Abstract
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.
Keywords: Acute respiratory failure; Artificial; COVID-19; Intensive care units; Nicotine; Nicotinic receptor; Randomized trial; Ventilation.