Aggressive Smoking Cessation for Acute Coronary Syndrome

(ASAP Trial)

Recruiting at 17 trial locations

Overseen By Hassan Mir

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: 12 weeks

798 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of aggressive smoking cessation therapy for individuals at high risk of heart problems. It compares two treatment plans: one combining varenicline (a medication that helps reduce cravings) with nicotine e-cigarettes, and another using only varenicline. The trial targets individuals who smoke at least 10 cigarettes a day, are motivated to quit, and have recently experienced heart-related issues such as a heart attack or unstable chest pain. Participants must commit to following the treatment plan and attending follow-up appointments for a year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that varenicline, a key component of the trial treatments, is safe for individuals with a history of heart problems. Studies have found that it does not affect heart rate or blood pressure and might even lower the risk of heart-related deaths. Using varenicline soon after heart procedures is also considered safe.

There is less specific information about combining varenicline with nicotine e-cigarettes. However, nicotine replacement therapies, such as e-cigarettes, are generally regarded as safe options for quitting smoking. Some reviews suggest they are well-tolerated, but more studies are needed to confirm their safety in all situations.

Overall, the treatments under study are based on existing therapies known to be safe for many people. This trial phase indicates that these treatments have already passed initial safety checks. Participants should still be monitored for any side effects, as with any medical treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for smoking cessation after acute coronary syndrome because they combine existing therapies in innovative ways. The combination therapy arm uses varenicline along with nicotine e-cigarettes and counseling, offering a multi-faceted approach that targets both psychological and physiological aspects of addiction. This is distinct from traditional methods like nicotine patches or gum, as e-cigarettes may provide a more satisfying alternative for smokers by mimicking the hand-to-mouth action of smoking. The varenicline plus counseling arm leverages varenicline's unique mechanism, which partially stimulates nicotine receptors to reduce cravings and withdrawal symptoms, potentially offering a more effective solution than nicotine replacement therapies alone. These approaches could provide more comprehensive support for people who need to quit smoking urgently after a heart attack or similar event.

What evidence suggests that this trial's treatments could be effective for smoking cessation in patients with acute coronary syndrome?

Research has shown that varenicline is one of the most effective treatments for quitting smoking. Studies have found that it works well alone or with other treatments. For individuals with heart problems, quitting smoking with varenicline can reduce the risk of heart issues by 35%. In this trial, one group of participants will receive Varenicline Plus Counseling.

Another group will receive a combination of varenicline with nicotine e-cigarettes plus counseling. Using varenicline with nicotine e-cigarettes also appears promising. One study found that both varenicline and e-cigarettes helped people quit smoking. Overall, combining medication and counseling usually leads to better results in quitting smoking. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation

Approved in European Union as Champix for:

• Smoking cessation

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+

Published Research Related to This Trial

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]

Smoking cessation is crucial for health, and psychiatric nurses should actively support patients in using therapies like varenicline (Chantix) to quit smoking.

Recent research has raised safety concerns about varenicline, including its potential links to neuropsychiatric side effects, seizures, and interactions with alcohol, which clinicians need to consider when recommending this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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 the EVITA trial involving 302 patients with acute coronary syndrome, varenicline significantly increased smoking abstinence rates at 52 weeks, with 39.9% of participants abstinent compared to 29.1% in the placebo group.

Despite the efficacy of varenicline in promoting smoking cessation, about 60% of patients still returned to smoking, indicating that while the treatment is beneficial, long-term abstinence remains a challenge.

NCBI (Pubmed)

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. Windle, SB., Dehghani, P., Roy, N., et al.[2019]

In a study of 302 smokers hospitalized with acute coronary syndrome, initiating varenicline treatment in-hospital significantly increased smoking abstinence rates at 24 weeks compared to placebo, with 47.3% of the varenicline group remaining abstinent versus 32.5% in the placebo group.

The safety profile of varenicline was comparable to placebo, with similar rates of serious adverse events and major cardiovascular events, suggesting it is a safe option for smoking cessation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome. Eisenberg, MJ., Windle, SB., Roy, N., et al.[2018]

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]

Varenicline, a medication used for smoking cessation, has been linked to serious cardiovascular events, including pulmonary thromboembolism (PTE), which may occur even in patients without pre-existing cardiovascular conditions.

A case report highlighted a probable association between varenicline and PTE, indicating that this adverse effect should be considered when prescribing the medication, especially since the patient had a low risk for such events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taking varenicline for smoking cessation: A rare cause of pulmonary thromboembolism with infarction. Lee, SH., Yun, SJ., Ryu, S., et al.[2017]

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]

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]

A case study of a 52-year-old man with cardiovascular disease showed that varenicline was safely used for 9 months to help him quit smoking, demonstrating its potential effectiveness in high-risk patients.

The combination of varenicline and intensive behavioral counseling not only helped the patient achieve smoking abstinence but also highlighted the importance of promoting smoking cessation in individuals with cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended varenicline treatment in a severe cardiopathic cigarette smoker: a case report. Munarini, E., Marabelli, C., Pozzi, P., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8425133/

Looking Back and Going Forward: Roles of Varenicline ... Varenicline and ECs have data suggesting efficacy for smoking cessation; however, unlike varenicline, ECs were not effective in all studies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11856351/

Smoking Cessation Strategies After Acute Coronary Syndrome Data suggest that greater success can be achieved in smoking cessation with a combination of pharmacological and non-pharmacological treatment.

3. acc.org acc.org/Latest-in-Cardiology/Journal-Scans/2024/06/24/15/43/electronic-cigarettes-vs-varenicline

Cigarettes vs. Varenicline for Smoking Cessation in Adults This randomized clinical trial found that varenicline and nicotine-containing ECs were both effective in helping individuals to quit smoking ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064257

Initiation of Varenicline in People Hospitalized for Acute ... In conclusion, varenicline may be the most effective smoking cessation pharmacotherapy available for patients with ACS. Given the tenacity of ...

5. ajconline.org ajconline.org/article/S0002-9149(18)30159-0/abstract

Smoking Cessation in Patients With Acute Coronary ... Behavioral interventions produced significantly improved abstinence rates at 6 and 12 months. However, these studies had substantial limitations ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6145797/

Cardiovascular Safety of Varenicline, Bupropion, and ... This randomized clinical trial evaluates the cardiovascular risk associated with use of varenicline, bupropion, and nicotine replacement therapy in individuals ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308815

Electronic Nicotine-Delivery Systems for Smoking Cessation Few trials have systematically collected data on prespecified safety outcomes and confirmed them by reviewing participants' medical records.