TY - JOUR
T1 - Cytisine for smoking cessation in patients with tuberculosis
T2 - a multicentre, randomised, double-blind, placebo-controlled phase 3 trial
AU - Dogar, Omara
AU - Keding, Ada
AU - Gabe, Rhian
AU - Marshall, Anna-Marie
AU - Huque, Rumana
AU - Barua, Deepa
AU - Fatima, Razia
AU - Khan, Amina
AU - Zahid, Raana
AU - Mansoor, Sonia
AU - Kotz, Daniel
AU - Boeckmann, Melanie
AU - Elsey, Helen
AU - Kralikova, Eva
AU - Parrott, Steve
AU - Li, Jinshuo
AU - Readshaw, Anne
AU - Sheikh, Aziz
AU - Siddiqi, Kamran
AU - TB & Tobacco Consortium
N1 - Funding Information:
The study was funded by the European Union Horizon 2020 research and innovation programme (680995). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the European Commission. We thank Aflofarm for providing the study drug at no cost. AS is supported by BREATHE-The Health Data Research Hub for Respiratory Health [MC_PC_19004] funded through the UK Research and Innovation Industrial Strategy Challenge Fund via the Medical Research Council and delivered through Health Data Research UK.
Funding Information:
The study was funded by the European Union Horizon 2020 research and innovation programme (680995). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the European Commission. We thank Aflofarm for providing the study drug at no cost. AS is supported by BREATHE-The Health Data Research Hub for Respiratory Health [MC_PC_19004] funded through the UK Research and Innovation Industrial Strategy Challenge Fund via the Medical Research Council and delivered through Health Data Research UK.
Publisher Copyright:
© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2020/11
Y1 - 2020/11
N2 - Background Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan.Methods We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1.5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete.Findings Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32.4%) participants in the cytisine group and 366 (29.7%) participants in the placebo group had achieved continuous abstinence (risk difference 2.68%, 95% CI -0.96 to 6.33; relative risk 1.09, 95% CI 0.97 to 1.23, p=0.114). 53 (4.3%) of 1239 participants in the cytisine group and 46 (3.7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which induded 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication.Interpretation Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
AB - Background Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan.Methods We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1.5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete.Findings Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32.4%) participants in the cytisine group and 366 (29.7%) participants in the placebo group had achieved continuous abstinence (risk difference 2.68%, 95% CI -0.96 to 6.33; relative risk 1.09, 95% CI 0.97 to 1.23, p=0.114). 53 (4.3%) of 1239 participants in the cytisine group and 46 (3.7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which induded 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication.Interpretation Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
KW - TOBACCO
KW - ADHERENCE
KW - SMOKERS
U2 - 10.1016/S2214-109X(20)30312-0
DO - 10.1016/S2214-109X(20)30312-0
M3 - Article
SN - 2214-109X
VL - 8
SP - E1408-E1417
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 11
ER -