Tuberculosis (TB) and tobacco

• Register: ISRCTN
• Last refreshed on: 12 September 2022
• Main ID: ISRCTN43811467
• Date of registration: 31/03/2016
• Prospective Registration: Yes
• Primary sponsor: University of York (UK)
• Public title: Tuberculosis (TB) and tobacco
• Scientific title: Tobacco cessation within TB programmes: a ‘real world’ solution for countries with dual burden of disease
• Date of first enrolment: 01/06/2017
• Target sample size: 2388
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN43811467
• Study type: Interventional
• Study design: Double-blind randomised parallel-group placebo-controlled interventional trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

Bangladesh, Pakistan

Contacts

• Name: Omara Dogar

Key inclusion & exclusion criteria

Inclusion criteria:
Current inclusion criteria as of 04/09/2017:
1. Age at least 15 years (counted as adult TB patients in Pakistan) and 18 years in Bangladesh
2. Able to provide consent
3. Diagnosed with pulmonary tuberculosis (PTB) (smear positive or negative) in the last four weeks
4. Currently smokes tobacco
5. Willing to quit tobacco use

Previous inclusion criteria:
1. Age at least 15 years (counted as adult TB patients in Pakistan and Bangladesh) and at least 18 years in Nepal
2. Able to provide consent
3. Diagnosed with pulmonary tuberculosis (PTB) (smear positive or negative) in the last four weeks
4. Currently smokes tobacco
5. Willing to quit tobacco use

Exclusion criteria:
Patients anticipated to have adverse effects either due to the study treatment or research burden, will be excluded. These will include those who are/have:
1. Retreatment TB, MDR TB, Miliary or Extra-pulmonary TB
2. Currently receiving Streptomycin (Category II anti-TB medication) and/or Para Amino Salicylic Acid (PASA)
3. Currently using any pharmacotherapy for tobacco dependence
4. Pregnant, lactating, or planning to become pregnant
5. Had myocardial infarction, stroke, or an attack of severe angina within the previous two weeks
6. Uncontrolled high blood pressure despite being on medication
7. Severe renal impairment (requiring dialysis)
8. Suffering from schizophrenia or known to be diagnosed with epilepsy


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Smoking cessation in pulmonary TB patients
Not Applicable

Intervention(s)

Arm 1: Cytisine + Behavioural Support
Arm 2: Placebo + Behavioural Support

Cytisine:
Participants allocated to Arm 1 will receive their first five days' cytisine supply on the day of trial enrolment (i.e. Day 0) and will be asked to quit tobacco use on the fifth day. Cytisine is a plant alkaloid and a partial agonist of nicotinic acetylcholine receptors (nAChRs). Cytisine has a short half-life of 4.8 hours, and is rapidly eliminated from the body. Its mechanism of action is similar to the effect of nicotine. It competes with nicotine on the nicotine receptors, which shortens the period of interaction of nicotine with the respective receptors and hence leads to a gradual reduction and elimination of existing psychological nicotine dependence in smokers. For this study hard capsules containing 1.5 mg of cytisine will be used. These capsules have a shelf life of 2 years.

Placebo:
Participants allocated to Arm 2 will receive placebo. By virtue of being a double-blind trial, patients allocated to Arm 2 will be dispensed the placebo in exactly the same manner as cytisine.

Behavioural support:
An adapted version of a pre-developed and proven effective Behavioural Support intervention to help people to quit smoking and smokeless tobacco use will be delivered to all enrolled patients by the clinical team (Health Worker/TB paramedic), irrespective of their treatment arm. This consists of two face-to-face sessions delivered at day 0 and day 5 (+2) and which last 10 and 5 minutes, respectively. The sessions will be structured using an educational flipbook; the session on day 0 will be aimed at encouraging tobacco users to see themselves as non-users,

Primary Outcome(s)

Continuous abstinence at six months (self-report of tobacco use not more than five cigarettes/bidis/water pipe sessions/chew after the quit date), which is biochemically verified by Carbon Monoxide (CO) level of <10ppm and cotinine dip-stick level of < 3 in urine (Level 3 =100-200ng/mL cotinine), if using smokeless tobacco as well.

Secondary Outcome(s)

Abstinence, Lapses and Relapses
Based on self-report alone or on the combination of self-report and CO/cotinine levels, these will include:
1. Point abstinence, defined as a self-report of not using tobacco in the previous 7 days at weeks 5 and 12, and verified by a CO level of <10ppm (or cotinine level < 3 for concomitant SLT users), at months 6 and 12.
2. Continuous abstinence at month 12 (only five instances of tobacco use allowed), biochemically verified as for the primary outcome at month 6.
3. Early-lapse, defined by a self-report of tobacco use (even once) after the quit date but having point abstinence at week 5.
4. Late-lapse, defined by a self-report of tobacco use (even once) between week 5 and week 12 but showing point abstinence at week 5 and week 12.
5. Early-relapse, defined by point abstinence at week 5 but a tobacco use status in later assessments.
6. Late-relapse, defined by point abstinence at week 5 and week 12 but a tobacco use status at month 6.

TB outcomes
1. Clinical outcome: an eight-point clinical score (TB score) will be used to assess clinical outcome at baseline, week 5, 9, 12 and months 6 and 12. The score consists of signs and symptoms of TB (cough, chest pain, dyspnoea, anaemic conjunctivae, body mass index (BMI) <18 kg/m2, BMI <16 kg/m2, mid-upper arm circumference (MUAC) <220 mm, and MUAC <200 mm), each contributing one point.
2. Laboratory-based outcome: sputum conversion results at weeks 5, 9 and months 6 and 12, of those that were sputum positive at the time of diagnosis.
3. X-ray-based outcome: patients' chest X-rays taken at baseline, week 9 and months 6 and 12 will be graded according to the National Tuberculosis Association of the USA as normal, minimal, moderately advanced and far advanced TB
4. Programme outcomes: the proportion of treatment success (including cured and completed treatment), treatment failure, defaulted and died will be recorded from TB register (TB03) at month 6, and relapse will be assessed at month 12 follow-up.

Nicotine Dependency scales
A translated version of the Mood and Physical Symptoms Scale (MPSS) in Bengali, Nepali and Urdu will be administered at baseline, weeks 5, 12, and at months 6 and 12. The frequency and strength of urge to smoke will also be assessed using a translated version of Strength of Urges to Smoke (SUTS) questions that will be administered at baseline, weeks 5, 12, and months 6 and 12. The translated scales will be assessed for their validity and reliability in the study population.

Adverse Events assessment
Adverse events will be classified using Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC), which will be monitored at each visit (as a part of the CRF), explicitly prompting for symptoms relating to possible Investigational Medicinal Product toxicities.

Secondary ID(s)

N/A

Source(s) of Monetary Support

European Commission

Ethics review

Status:
Approval date:
Contact:

1. Health Sciences Research Governance Committee (HSRGC) at the University of York, UK, 12/02/2016 2. National Bio-ethics Committee, Pakistan Medical Research Council, 06/06/2016, ref: No.4-87/16/NBC-200 Part-B/RDC/4197 3. National Research Ethics Committee, Bangladesh Medical Research Council, 31/08/2016, Ref: BMRC/NREC/2016-2019/1475)

Results

• Results available: Yes
• Date Completed: 31/10/2019