Aggressive Smoking Cessation Trial (ASAP)

Cardiovascular Diseases Clinical Trial

— ASAP  

Official title:

Aggressive Smoking Cessation Therapy Among People at Elevated Cardiovascular Risk (ASAP) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05257629
• Other study ID #: ASAP-001, Version 9
• Status: Recruiting
• Phase: Phase 3
• Start date: February 2, 2023
• Est. completion date: March 7, 2027

Study information

• Verified date: June 2024
• Source: Sir Mortimer B. Davis - Jewish General Hospital
• Contact: Tabitha Finch
• Phone: 514-340-8222
• Email: ASAP.Trial[@]ladydavis.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ASAP Trial is a 5-year, multi-centre, randomized controlled trial that will assess the efficacy, safety, and tolerability of aggressive smoking cessation therapy among people at elevated cardiovascular risk. It will recruit 798 adult patients smoking on average at least 10 conventional (tobacco) cigarettes per day who are motivated to quit smoking and have either been diagnosed with ACS requiring hospitalization or are outpatients at elevated cardiovascular risk. Patients will be randomized (1:1) to one of two treatment arms: (1) combination therapy of varenicline and nicotine e-cigarettes plus counseling or (2) varenicline plus counseling for 12 weeks, with 52-week follow-up.

Description:

Background and Importance:

People who smoke are at an elevated risk of developing cardiovascular disease (CVD). Those who have an acute coronary syndrome (ACS), including myocardial infarction and unstable angina, and continue to smoke have a 35% increased risk of reinfarction or death compared with those who quit. Our previous smoking cessation trials have established varenicline (Champix) as the "gold standard" for patients with CVD. However, more than 50% of patients motivated to quit who receive varenicline for 12 weeks immediately post-ACS will return to smoking within 6 months. Therefore, more effective smoking cessation strategies are needed. Based on newly available data from randomized controlled trials (RCTs), including our E3 Trial, which suggest that nicotine e-cigarettes are more efficacious for smoking cessation than other nicotine replacement therapies and counseling alone, we propose to combine varenicline and nicotine e-cigarettes (aggressive smoking cessation therapy). The proposed aggressive therapy is a novel approach needed now to increase abstinence in people at elevated cardiovascular risk.

Goal(s)/Research Aims:

The Aggressive Smoking Cessation Therapy Among People at Elevated Cardiovascular Risk (ASAP) Trial is a 5-year, multi-centre RCT that will assess the efficacy, safety, and tolerability of aggressive smoking cessation therapy among people at elevated cardiovascular risk. The specific aims are:

1. To assess the efficacy of combination therapy (varenicline and nicotine e-cigarettes) versus varenicline alone for 12 weeks, in terms of biochemically-validated 7-day point prevalence and continuous smoking abstinence, and ≥50% reduction in daily cigarette consumption at 24 and 52 weeks among people at elevated cardiovascular risk.

2. To describe the safety and tolerability of varenicline combined with nicotine e-cigarettes, in terms of serious adverse events (SAEs), adverse events (AEs), treatment discontinuation due to side effects, and therapy adherence over the 12-week treatment period.

Methods/Approaches/Expertise:

A total of 798 participants will be randomized 1:1 to: (1) varenicline and nicotine e-cigarettes (aggressive smoking cessation therapy), or (2) varenicline alone for 12 weeks, with follow-up of 52 weeks. Both arms will receive individual smoking cessation counseling. Participants randomized to aggressive therapy (varenicline and nicotine e-cigarette) will be given funds to cover the purchase of e-cigarettes and nicotine cartridges. Funds will be provided at baseline for the first 4 weeks of e-cigarette use. Participants who follow the e-cigarette purchasing instructions and provide receipts at subsequent clinic visits will be provided additional funds at week 4 (for weeks 4 to 8) and reimbursed at week 12 (for weeks 8 to 12). Participants will begin varenicline (titrated to 1.0 mg twice daily) and counseling at baseline, and e-cigarette use (if applicable) after the baseline visit. Eligible people will have or be at elevated risk of developing CVD, self-identify as regular smokers (≥10 cigarettes/day for ≥1 year), and be motivated to quit. They will complete telephone follow-ups at weeks 1, 2, 8, and 18, and clinic visits at weeks 4, 12, 24, and 52. We will collect information about self-reported smoking, treatment adherence, and adverse events. Self-reported smoking abstinence will be biochemically-validated at clinic visits using exhaled carbon monoxide (≤10 ppm). The primary endpoint will be biochemically-validated 7-day point prevalence smoking abstinence at 24 weeks. With 399 participants per arm and an alpha of .05, we will have 80% power to detect a ≥10% difference in abstinence at 24 weeks. The ASAP Trial will be conducted by a highly experienced team of researchers and enrolling centres, who have previously completed three smoking cessation RCTs, including two in cardiac patients.

Expected Outcomes:

Smoking cessation is essential to reduce morbidity and mortality in this high-risk patient population. ASAP will provide regulators, health care professionals, and smokers with important information about the efficacy of aggressive varenicline and nicotine e-cigarettes therapy for smoking cessation in people at an elevated cardiovascular risk.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 798
• Est. completion date: March 7, 2027
• Est. primary completion date: September 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients currently hospitalized or being discharged from hospital who have suffered an ACS, defined as follows:

i. MI, defined by positive troponin T, troponin I, or CK-MB levels (as defined by institution-specific cut-offs) and = 1 of the following:

1. Ischemic symptoms for = 20 min;

2. Electrocardiogram (ECG) changes indicative of ischemia (ST-segment elevation or depression);

3. Development of pathological Q waves on the ECG

ii. Unstable angina with significant coronary artery disease, defined by all of the following:

1. Ischemic symptoms for = 20 min;

2. ECG changes indicative of ischemia (ST-segment changes);

3. At least one lesion = 50% on angiogram performed during the current hospitalization.

[Note: patients who undergo cardiac catheterization or percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery will be eligible provided they are able to start varenicline in-hospital and nicotine e-cigarette at discharge.]

OR

Outpatients with the following diagnoses/conditions:

i. Cardiovascular:

1. Coronary artery disease documented with angiography or coronary CT;

2. Previous ACS, MI, stable or UA;

3. Previous coronary revascularization (e.g. PCI or CABG). ii. Renovascular:

a. Chronic kidney disease. iii. Cerebrovascular:

a. Previous cerebral infarction or transient cerebral ischemic attack. iv. Peripheral vascular:

1. Abdominal aortic aneurysm > 3.0 cm or previous aortic aneurysm surgery;

2. Ankle-brachial pressure index of < 0.9 or intermittent claudication;

3. Documented carotid artery disease;

4. Lower-limb amputation;

5. Previous lower-limb bypass surgery or angioplasty.

v. =1 risk factors:

1. BMI = 27 kg/m2;

2. Dyslipidemia;

3. Family history (first degree relative: parents or siblings only) of coronary heart disease or stroke before the age of 60 years;

4. Hypertension;

5. Males aged = 55 years/females aged = 60 years;

6. Diabetes mellitus. vi. Heart-related conditions:

1. Atrial fibrillation or flutter;

2. Cardiomyopathy;

3. Heart failure;

4. Left ventricular hypertrophy (evidenced by echocardiography or ECG);

5. Valvular disease (evidenced by echocardiography).

2. Smoked on average = conventional cigarettes/day for the past year;

3. Age =18 years;

4. Motivated to quit smoking according to the Motivation To Stop Scale (MTSS) (= level 5);

5. Able to understand and provide informed consent in English or French;

6. If randomized to the combination arm (varenicline and e-cigarette plus counseling), willing and able to purchase e-cigarettes with the following properties: rechargeable, closed system that uses sealed cartridges or pods, tobacco or no flavor only, and nicotine strength of 20 mg/ml (2%) or less;

7. Likely to be available for 52 weeks of follow-up.

Exclusion Criteria:

1. Pregnant or lactating females;

2. Use of any of the following in the 30 days prior to eligibility assessment:

i. Varenicline or bupropion for smoking cessation; ii. Nicotine or non-nicotine e-cigarettes; iii. Other anti-craving medication (e.g., naltrexone, acamprosate) with the potential to alter substance-seeking behaviors;

3. Use of nicotine replacement therapy (NRT) in the 7 days prior to eligibility assessment [Note: If participant is prescribed non-study NRT while hospitalized, they can continue using the non-study NRT until being discharged, even while taking the investigational products. Upon discharge, use of the non-study NRT should be stopped.];

4. Use of varenicline or e-cigarettes (nicotine or non-nicotine) for =14 days consecutively in the past year;

5. Previous serious adverse reaction to varenicline and/or e-cigarettes (nicotine or non-nicotine);

6. NYHA or Killip Class III or IV at the time of randomization;

7. Any unstable psychiatric disorder (as per enrolling physician);

8. Renal impairment with creatinine levels =2 times upper limit of normal or eGFR =15;

9. Use of any illegal drugs in the past year;

10. Planned use of cannabis (smoked) or other tobacco products (smoked or other) during the study period. [Note: use of cannabis which is not smoked is permitted (e.g., edibles, ingested or vaped oils). However, methods which involve combustion could invalidate biochemical validation via exhaled carbon monoxide.]

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Cardiovascular Diseases

Intervention

Combination Product:
• Combination Therapy Arm (Varenicline and Nicotine E-Cigarettes Plus Counseling)
Varenicline and nicotine e-cigarettes plus counseling

Other:
• Varenicline Plus Counseling
Varenicline plus counseling

Locations

Country	Name	City	State
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	Dr. Georges-L.-Dumont University Hospital Center	Moncton	New Brunswick
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Centre Hospitalier de L'Universite de Montreal	Montréal	Quebec
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec	Quebec City	Quebec
Canada	NL Health Sciences	Saint John's	Newfoundland and Labrador
Canada	Royal University Hospital	Saskatoon	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
Sir Mortimer B. Davis - Jewish General Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with 7-day point prevalence smoking abstinence at 4, 12, and 52 weeks	Biochemically-validated 7-day point prevalence smoking abstinence at 4, 12, and 52 weeks, defined as self-reported abstinence in the past 7 days with exhaled carbon monoxide = 10 ppm.	4, 12, and 52 weeks
Other	Number of patients with continuous abstinence at 4, 12, 24, and 52 weeks	Biochemically-validated continuous abstinence at 4, 12, 24, and 52 weeks, defined as self-reported abstinence since baseline with exhaled carbon monoxide = 10 ppm at all follow-up visits.	4, 12, 24, and 52 weeks
Other	Number of prolonged smoking abstinence at all follow-up visits	Prolonged abstinence, defined as self-reported abstinence at all follow-up visits after an initial 2 weeks grace period with exhaled carbon monoxide = 10 ppm at 4, 12, 24, and 52 weeks.	4, 12, 24, and 52 weeks
Other	Change in daily cigarette consumption at all other weeks	Change in self-reported daily conventional cigarette consumption from baseline at weeks 1, 2, 4, 8, 12, 18, and 52.	1, 2, 4, 8, 12, 18, and 52 weeks
Other	Number of patients with =50% reduction in daily cigarette consumption at all other weeks	Proportion of participants with =50% reduction in self-reported daily cigarette consumption from baseline at weeks 1, 2, 4, 8, 12, 18, and 52.	1, 2, 4, 8, 12, 18, and 52 weeks
Other	Number of participants with point prevalent abstinence or =50% reduction in daily cigarette consumption at all other weeks	Composite endpoint of point prevalent abstinence or =50% reduction daily cigarette consumption at weeks 1, 2, 4, 8, 12, 18, and 52.	1, 2, 4, 8, 12, 18, and 52 weeks
Other	Spirometry measurements (subset) at all other clinic visits	For the sub-set of 100 patients undergoing spirometry measurements, differences in FVC, FEV1, and FEV1/FVC ratio as well as measures of small airways disease between pre- and post-bronchodilator at week 4, week 12, and week 52.	4, 12, and 52 weeks
Other	O2 Cost Diagram and COPD Assessment Test (subset) at all other clinic visits	For the sub-set of 100 patients undergoing spirometry measurements, the difference in the O2 Cost Diagram and the CAT at weeks 4, 12, and 52 compared to baseline.	4, 12, and 52 weeks
Other	Number of patients averaging =1 pill of varenicline/day	To describe the proportion of participants averaging =1 pill/day for varenicline over the treatment period	12 weeks
Other	To describe e-cigarette pattern of use	To describe the nicotine e-cigarette pattern of use during the treatment period in terms of self-reported average sessions per week, and puffs per session (7-day recall).	12 weeks
Primary	Number of participants with 7-day point prevalence smoking abstinence	Biochemically-validated 7-day point prevalence smoking abstinence at 24 weeks, defined as self-reported abstinence in the past 7 days with exhaled carbon monoxide = 10 ppm.	24 weeks
Secondary	Number of participants with continuous smoking abstinence	Biochemically-validated continuous abstinence at 4, 12, and 24 weeks, defined as self-reported abstinence since baseline with exhaled carbon monoxide = 10 ppm at all clinic follow-ups, and self-reported 0 cigarette smoked in the past 7 days at telephone follow-ups (1, 2, 8, and 18 weeks).	1, 2, 8, and 18 weeks
Secondary	Number of participants with prolonged smoking abstinence	Prolonged abstinence, defined as self-reported abstinence at all clinical and telephone follow-ups after an initial 2-week grace period with exhaled carbon monoxide = 10 ppm at 4, 12, and 24 weeks, and self-reported 0 cigarette smoked in the past 7 days at the 8, and 18 weeks telephone follow-ups	4, 8, 12, 18, and 24 weeks
Secondary	Change in daily cigarette consumption	Change in self-reported daily conventional cigarette consumption from baseline compared to 24 weeks.	24 weeks
Secondary	Number of participants with =50% reduction in daily cigarette consumption	Proportion of participants with =50% reduction in self-reported daily cigarette consumption from baseline compared to 24-weeks.	24 weeks
Secondary	Number of participants with point prevalent abstinence or =50% reduction in daily cigarette consumption at 24 weeks	Composite endpoint of point prevalent abstinence or =50% reduction in daily cigarette consumption at 24 weeks	24 weeks
Secondary	Frequency of Serious Adverse Events (SAEs)	The number of serious adverse events (SAE) reported over the 12 week treatment period.; A SAE is defined as an adverse event which requires in-patient hospitalization or prolongation of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability or incapacity, that is life-threatening, or that results in death.	12 weeks
Secondary	Frequency of Adverse Events (AEs)	The number of adverse events reported over the 12 week treatment period. An adverse event is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the trial drug, whether or not considered related to the e-cigarettes or varenicline.	12 weeks
Secondary	Frequency of drop-outs	The number of drop-outs due to side effects of the e-cigarettes or varenicline over the 12 week treatment period.	12 weeks
Secondary	Spirometry measurements (subset)	For a sub-set of 100 patients, 50 from each arm, randomized at 4-5 recruiting sites, undergoing spirometry measurements, differences in FVC, FEV1, and FEV1/FVC ratio as well as measures of small airways disease between pre- and post-bronchodilator at week 24 from baseline.	24 weeks
Secondary	O2 Cost Diagram and COPD Assessment Test (subset)	For the same sub-set of 100 patients undergoing spirometry measurements randomized at 4-5 recruiting sites, the difference in the O2 Cost Diagram and the CAT at week 24 from baseline.	24 weeks