Aggressive Smoking Cessation for Acute Coronary Syndrome

(ASAP Trial)

Recruiting in Palo Alto (17 mi)

+12 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Sir Mortimer B. Davis - Jewish General Hospital

Must be taking: Varenicline

Must not be taking: Bupropion, NRT, Anti-craving meds

Disqualifiers: Pregnancy, Unstable psychiatric disorder, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use certain smoking cessation aids like varenicline, bupropion, or nicotine replacement therapy shortly before or during the trial.

What data supports the effectiveness of this drug for smoking cessation in patients with acute coronary syndrome?

Research shows that varenicline, a drug used to help people stop smoking, was successful in achieving smoking abstinence in patients with acute coronary syndrome (ACS). Additionally, combining pharmacological treatments like varenicline with behavioral interventions, such as counseling, has shown the best results for helping people quit smoking after ACS. ^{1 2 3 4 5}

Is varenicline safe for use in humans?

Varenicline, used for smoking cessation, has been linked to some safety concerns, including potential cardiovascular issues like heart attacks and blood clots, as well as neuropsychiatric side effects and interactions with alcohol. While some studies suggest these risks may not be significantly higher than with a placebo, the FDA advises caution and close monitoring when prescribing varenicline. ^{6 7 8 9 10}

How does the drug combination of varenicline and nicotine e-cigarettes with counseling differ from other treatments for smoking cessation after acute coronary syndrome?

This treatment is unique because it combines varenicline, a medication proven to help people quit smoking, with nicotine e-cigarettes and counseling, aiming to enhance smoking cessation success after acute coronary syndrome. While varenicline alone has shown some success, the addition of e-cigarettes and counseling may provide a more comprehensive approach to help patients quit smoking effectively. ^{1 2 3 5 11}

Research Team

Eligibility Criteria

The ASAP trial is for adults over 18 who smoke at least 10 cigarettes a day, are hospitalized with Acute Coronary Syndrome (ACS), and want to quit smoking. They must understand English or French, be able to buy e-cigarettes if in the combination therapy group, and commit to a year-long follow-up. Excluded are those with recent use of varenicline or e-cigarettes, serious reactions to these products, severe heart failure, pregnancy, certain medications for quitting smoking or psychiatric disorders.

Inclusion Criteria

I can start varenicline in the hospital and use a nicotine e-cigarette after my heart procedure.

I have severe heart disease with symptoms and changes seen in tests during this hospital stay.

I am willing and able to buy specific e-cigarettes if needed for the study.

Exclusion Criteria

You have a mental health condition that is not currently well-managed.

Pregnant or lactating females

You have used nicotine or non-nicotine e-cigarettes in the 30 days before being admitted to the hospital for acute coronary syndrome.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either varenicline and nicotine e-cigarettes or varenicline alone, along with counseling for 12 weeks

12 weeks

Clinic visits at weeks 4 and 12; telephone follow-ups at weeks 1, 2, 8, and 18

Follow-up

Participants are monitored for smoking abstinence and adverse events after treatment

52 weeks

Clinic visits at weeks 24 and 52

Long-term Follow-up

Participants continue to be monitored for smoking abstinence and cardiovascular health outcomes

Additional 1 year

Treatment Details

Interventions

• Combination Therapy Arm (Varenicline and Nicotine E-Cigarettes Plus Counseling) (Behavioural Intervention)
• Varenicline Plus Counseling (Behavioural Intervention)

Trial Overview This study tests two methods to help people stop smoking after being hospitalized for ACS: one combines a drug called varenicline with nicotine e-cigarettes and counseling; the other uses just varenicline plus counseling. Participants will be randomly assigned to either method for 12 weeks and then checked on for up to a year.

Participant Groups

Group I: Varenicline Plus Counseling Experimental Treatment 1 Intervention

All patients will begin varenicline in-hospital upon randomization. For the first 3 days, patients will take a 0.5 mg tablet once a day. They will then take a 0.5 mg tablet twice a day for the following 4 days, and one 1 mg tablet twice a day from day 8 onward for the remainder of the 12-week treatment. Use will be monitored via self-report for telephone follow-ups and return of all unused tablets at the end of the treatment period. Should a patient experience severe side effects (such as headache, nausea, vomiting, dizziness, dyspepsia, fatigue, insomnia, abnormal dreams, constipation, or flatulence) on day 8 onward, the varenicline dose should be reduced from 1 mg twice daily to 0.5 mg twice daily prior to study medication discontinuation.

Group II: Combination Therapy Arm (Varenicline and Nicotine E-Cigarettes Plus Counseling) Active Control 1 Intervention

Patients in the combination therapy arm will be supplied funds and instructions for the purchase of e-cigarettes and cartridges/pods upon hospital discharge and at the week 4 and 12 clinic visits. As with standard NRTs such as the gum, inhaler, and lozenge, the investigators expect smokers will self-regulate administration according to their withdrawal symptoms. Use will be monitored via self-report for telephone follow-ups. At clinic visits, patients will be asked to bring their e-cigarettes, used and unused cartridges/pods, and purchasing receipts. Patients will be advised regarding the signs and symptoms of nicotine toxicity and of an allergic reaction.

Combination Therapy Arm (Varenicline and Nicotine E-Cigarettes Plus Counseling) is already approved in Canada for the following indications:

Approved in Canada as Tyrvaya for:

• Smoking cessation

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

61

Recruited

25,800+

Dr. Lucie Opatrny

Sir Mortimer B. Davis - Jewish General Hospital

President and Executive Director since 2023

MDCM and Master's in Epidemiology and Biostatistics from McGill University

Dr. Guy Rouleau

Sir Mortimer B. Davis - Jewish General Hospital

Chief Medical Officer since 2023

MD from McGill University

Findings from Research

The EVITA trial is investigating the efficacy of varenicline, a smoking cessation medication, in patients who have experienced an acute coronary syndrome (ACS), with 302 participants enrolled for a 12-week treatment period.

If proven effective, varenicline could significantly improve smoking cessation rates in ACS patients, potentially reducing their risk of reinfarction and death, thus enhancing secondary prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of the efficacy and safety of varenicline for smoking cessation after acute coronary syndrome: design and methods of the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome trial. Windle, SB., Bata, I., Madan, M., et al.[2016]

Pharmacological interventions for smoking cessation in patients with acute coronary syndrome (ACS) have shown mixed results, with only varenicline demonstrating success in achieving smoking abstinence, while nicotine replacement therapy and bupropion did not show significant benefits.

Behavioral interventions, particularly telephone counseling, were effective in promoting smoking cessation, especially in the acute setting, and the best outcomes were observed when combining both pharmacological and behavioral strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions for smoking cessation in patients admitted with Acute Coronary Syndrome: a review. Chehab, OM., Dakik, HA.[2018]

In a study of 72 smokers who quit smoking using varenicline, flow-mediated dilation (FMD), a measure of endothelial function, significantly improved after 20 weeks, indicating enhanced vascular function.

While varenicline therapy led to a significant reduction in exhaled carbon monoxide levels, it did not result in changes to nitroglycerin-induced vasodilation or brachial artery intima-media thickness, suggesting that the improvement in vascular function is primarily due to better endothelial health rather than structural changes in blood vessels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular Functional and Morphological Alterations in Smokers during Varenicline Therapy. Kobayashi, M., Takemoto, Y., Norioka, N., et al.[2017]

Among patients hospitalized for acute coronary syndrome (ACS), smoking cessation therapies show limited efficacy, with only varenicline demonstrating increased abstinence rates at 12 months in pharmacologic trials.

Behavioral interventions also improved smoking abstinence rates at 6 and 12 months, but the studies had significant limitations, highlighting the need for further research to establish effective smoking cessation guidelines for ACS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking Cessation in Patients With Acute Coronary Syndrome. Franck, C., Filion, KB., Eisenberg, MJ.[2022]

Varenicline, a medication used for smoking cessation since 2006, has been linked to serious cardiovascular events, including a case of acute coronary syndrome in a 30-year-old man without prior heart disease.

The Naranjo probability scale suggested that varenicline was a probable cause of the myocardial infarction, highlighting the need for caution when prescribing this medication, especially in patients with cardiovascular risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline-induced coronary thrombosis. Kalayci, A., Eren, A., Kocabay, G., et al.[2015]

Varenicline is an effective first-line smoking cessation aid, but its safety profile regarding serious cardiovascular events has been debated, with some reviews suggesting a nominally higher risk compared to placebo.

Despite some evidence indicating that serious cardiovascular risks may not be significantly increased with varenicline, the FDA recommends cautious prescribing and close monitoring, especially for patients with unstable cardiac conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline and cardiovascular adverse events: a perspective review. Chelladurai, Y., Singh, S.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of the efficacy and safety of varenicline for smoking cessation after acute coronary syndrome: design and methods of the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome trial. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Interventions for smoking cessation in patients admitted with Acute Coronary Syndrome: a review. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

Vascular Functional and Morphological Alterations in Smokers during Varenicline Therapy. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Smoking Cessation in Patients With Acute Coronary Syndrome. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Varenicline-induced coronary thrombosis. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Taking varenicline for smoking cessation: A rare cause of pulmonary thromboembolism with infarction. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Extended varenicline treatment in a severe cardiopathic cigarette smoker: a case report. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Varenicline and cardiovascular adverse events: a perspective review. [2021]

11. Canada pubmed.ncbi.nlm.nih.gov

Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital. [2019]