Evaluating Smoking Cessation Interventions for PWH in South Africa

Study Overview
=================
Brief Summary
-----------------
The overall objective of the study is to optimize a smoking cessation treatment package for people with HIV (PWH) that can be integrated into existing HIV care in South Africa.

Detailed Description
-----------------
This project will evaluate the main and interaction effects of four evidence-based smoking cessation components integrated within HIV care in South Africa: (1) intensive behavioural counselling, (2) peer support, (3) combination nicotine replacement therapy (c-NRT), and (4) varenicline. The investigators will also evaluate the implementation and cost-effectiveness of these interventions. This study is a balanced full factorial randomised trial of 660 adults with HIV and will be implemented in two diverse sites in Gauteng, South Africa representing both peri-urban and urban settings. Participants will be recruited via health care worker-referral or self-referral. Interested patients will be further screened for eligibility. Eligible participants will be administered written informed consent (see Informed Consent and Assent section below), and participants will be randomized into one of 16 study conditions for a 12-week intervention period. This will be an open-label trial; neither the participants nor study personnel will be blinded to treatment assignment post randomization, but randomization block assignment will be concealed from the study personnel who will be enrolling participants.

Official Title
-----------------
Evaluating Smoking Cessation Interventions for PWH in South Africa: Efficacy, Implementation, and Cost-effectiveness

Conditions
-----------------
HIV, Smoking Cessation, Comorbidities and Coexisting Conditions

Intervention / Treatment
-----------------
* Drug: Varenicline
* Drug: Nicotine patch
* Drug: Nicotine gum
* Behavioral: Intensive Behavioral Counselling
* Behavioral: Peer Counselling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years of age, and attend one of the selected study clinics, and have a confirmed diagnosis of HIV (evidenced by one of: clinic or hospital prescription for combination antiretroviral therapy (ART), or a current ART medication pack that has the patient's name documented thereon) and have been taking ART for at least three consecutive months (to ensure engagement in care at the recruitment clinic), and are current tobacco smokers (smoked at least 100 cigarettes in the subject's lifetime, have smoked daily for the past 30 days, have exhaled breath carbon monoxide (CO) ≥ 7 parts per million (ppm), and have a positive urine cotinine test), and either own or have household access to a mobile phone, and provide written informed consent. Exclusion Criteria: Currently (within the previous 14 days) receiving or using smoking cessation counselling or pharmacotherapy, or are unable to participate due to severity of medical illness, guided by a Karnofsky score of ≤ 40, or have a history of seizures, cancer, heart disease, stroke, myocardial infarction, stomach ulcers, kidney failure, or liver failure, or have generalized eczema or psoriasis, or have cognitive dysfunction or psychosis as defined by the Mini-International Neuropsychiatric Interview (M.I.N.I.), or have suicide risk as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS), or are pregnant, planning to become pregnant in the next four months, lactating, or are unwilling to use effective birth control, or have a history of adverse reactions to varenicline or nicotine patch, or are not planning to continue to receive care at the clinic for the next 52 weeks. In the opinion of the attending investigator are not a candidate for the clinical trail.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The investigators will conduct a 4-factor, balanced full factorial randomized controlled trial to evaluate the main and interaction effects of these 2-level interventions in one peri-urban and one urban setting in South Africa. The investigators will randomize adults with HIV who are current smokers into 1 of 16 possible combinations of the four intervention components.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive Behavioral Counselling<br>Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice. ]. | Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>|
| Experimental: Peer Support<br>Participants randomized to receive Peer Support will be engaged by participants' own peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request. | Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: c-NRT<br>A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package. Participants will be provided with education on its use, including where and how to place a patch, strength of patches to use and how to taper, not smoking while using the patch, and using gum ad hoc; the investigators will also discuss possible side effects. Participants will be given a number to call should the participants require assistance, and weekly calls will be made to participants to screen for adverse events and monitor adherence; calls will taper to every other week after four weeks. | Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;|
| Experimental: Varenicline<br>At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician according to randomization into the varenicline condition and participants will be provided with education on its use. Participants will be instructed to begin taking varenicline one week prior to participants' quit date and for 11 weeks following quit date. Participants will be given a number to call should the participants require assistance, and weekly calls will be made to participants to screen for adverse events and to monitor adherence; calls will taper to every other week after four weeks. | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>|
| No Intervention: Control<br>No intervention | |
| Experimental: Varenicline & c-NRT<br>Varenicline & c-NRT | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;|
| Experimental: Peer Support & Varenicline<br>Peer Support & Varenicline | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: c-NRT & Peer Support<br>c-NRT & Peer Support | Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: c-NRT & Peer Support & Varenicline<br>c-NRT & Peer Support & Varenicline | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: Intensive Behavioral Counseling & Varenicline<br>Intensive Behavioral Counseling & Varenicline | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>|
| Experimental: Intensive Behavioral Counseling & c-NRT<br>Intensive Behavioral Counseling & c-NRT | Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>|
| Experimental: Intensive Behavioral Counseling & Varenicline & c-NRT<br>Intensive Behavioral Counseling & Varenicline & c-NRT | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>|
| Experimental: Intensive Behavioral Counseling & Peer Support<br>Intensive Behavioral Counseling & Peer Support | Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: Intensive Behavioral Counseling & Peer Support & Varenicline<br>Intensive Behavioral Counseling & Peer Support & Varenicline | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: Intensive Behavioral Counseling & Peer Support & c-NRT<br>Intensive Behavioral Counseling & Peer Support & c-NRT | Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|
| Experimental: Intensive Behavioral Counseling & Peer Support & c-NRT & Varenicline<br>Intensive Behavioral Counseling & Peer Support & c-NRT & Varenicline | Drug: Varenicline<br>* At enrolment, a 12-week course of varenicline in the commercially available package will be dispensed by a study clinician.<br>Drug: Nicotine patch<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: combination nicotine replacement therapy;Drug: Nicotine gum<br>* A 12-week course of nicotine patches and nicotine gum will be dispensed to the participant by the counsellor according to randomization into the c-NRT condition. c-NRT will be provided per label instructions given number of cigarettes the participant smokes per day and will be provided in the commercially available package.<br>* Other names: nicotine replacement;Behavioral: Intensive Behavioral Counselling<br>* Participants randomized to the Intensive Behavioural Counselling condition will receive in-person intensive ( 45 minutes) behavioural counselling in the clinic at screening and at weeks 2, 4, 8, and 12. Additionally, on non-clinic visit weeks participants will receive (1) one phone call each week from the clinic counsellor, and (2) two text messages each week providing encouragement and advice.<br>Behavioral: Peer Counselling<br>* Participants randomized to the Peer Support condition will be engaged by a peer counsellor over weeks -2 to 12. Peer counselling will follow a flexible framework for contact with participants, which will include in-person and phone-based check-ins, depending upon individual participant preference. Peer counsellors will visit the counsellors' assigned participant in-person at participants' home, workplace, or other setting based on participant preference at least during weeks -2, 2, 4, 8 and 12; additional in-person contact will be provided upon participant request.<br>* Other names: Peer Support;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day point prevalence tobacco abstinence at 52 weeks | Verified by exhaled breath CO < 7ppm and a negative urine cotinine test. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day point prevalence tobacco abstinence at 26 weeks | Verified by exhaled breath CO < 7ppm and a negative urine cotinine test. Urine cotinine will be excluded as an indicator of abstinence for those self-reporting c-NRT use in the preceding week. | 26 weeks | 
| 7-day point prevalence tobacco abstinence at 12 weeks | Verified by exhaled breath CO < 7ppm and a negative urine cotinine test. Urine cotinine will be excluded as an indicator of abstinence for those self-reporting c-NRT use in the preceding week. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Smoking Cessation, Combination NRT, Varenicline, Behavioral Counselling, Peer Counseling