Background

Tobacco smoking remains a significant global health issue, claiming over 8 million lives annually [1]. In Germany alone, smoking-related cardiovascular disease and cancers cause approximately 127,000 deaths each year, with smokers typically experiencing a lifespan reduction of 9 to 15 years compared to non-smokers [2,3,4,5,6]. Nevertheless, according to the German Federal Ministry of Health, in Germany 23.8% of people aged 18 years and over still smoke, with a higher prevalence among men (27%) compared to women (20.8%) [7]. The DEBRA study 2023 (German Study on Tobacco Use) provides recent data, revealing a further increase of adult smoking rates soaring to 34.4% [8].

German guideline for smoking cessation

Among the major modifiable risk factors for mortality, smoking represents the one where modifications (i. e., smoking cessations) are most effective. The German guideline for smoking cessation entitled "S3 Guideline Smoking and Tobacco Addiction: Screening, diagnostic and treatment” [9] and published in 2021 are aimed at guiding physicians in facilitating smoking cessation among their patients. These recommendations include:

- Brief counseling: Brief counseling for smokers to achieve smoking cessation should be offered in medical, nursing and psychosocial health care settings (recommendation grade A).

- Behavioral therapy group interventions: Behavioral therapy group interventions aimed to achieving tobacco abstinence should be offered in medical, psychotherapeutic and psychosocial health care (recommendation grade A).

- Nicotine replacement therapy (NRT): The use of NRT including nicotine gum, nicotine inhalers, nicotine lozenges, nicotine nasal sprays, nicotine mouth sprays and nicotine patches, should be offered to patients (recommendation grade A).

- Varenicline, bupropion, cytisine: The use of varenicline, bupropion and cytisine should be offered (recommendation grades: varenicline: A, bupropion: A, cytisine: 0).

However, the implementation and acceptance of these recommendations remain uncertain as their application is voluntary and there is no data on their efficacy. Furthermore, Champix® (active ingredient: varenicline) and Zyban® (active ingredient: bupropion) are currently unavailable, thus making it impossible to adhere to the recommended treatment guideline.

Switching to alternative nicotine delivery systems (ANDS), such as e-cigarettes or tobacco heaters, is available as an extension of smoking cessation efforts. While these devices may reduce exposure to harmful substances found in tobacco, their long-term health implications remain unclear. Nonetheless, emerging evidence, including a Cochrane Review from 2023 [10] suggests a potential role for nicotine-containing e-cigarettes in smoking cessation. The German guideline for smoking cessation [9] does not contain an official recommendation regarding the use of ANDS in smoking cessation measures. In accordance with the recommendation from the current German guideline for smoking cessation, we will only consider using e-cigarettes and tobacco heaters to support tobacco abstinence once other evidence-based measures have failed or been rejected and information on known risks has been provided to participants.

Peripheral arterial disease (PAD)

PAD, a common consequence of smoking, presents unique challenges in smoking cessation efforts. Smokers with PAD not only face heightened disease progression risks [11, 12] but also encounter increased peri-operative complications such as major amputations and death [13, 14] compared to non-smokers with PAD. Specifically, the risk of primary failure of endovascular treatment of an iliac lesion is 2.46 times higher in smokers than in patients who do not smoke [13].

A recent meta-analysis underscored the uncertain efficacy of smoking cessation programs tailored to PAD patients, highlighting the need for targeted interventions [15, 16]. This meta-analysis, which included six randomized-controlled trials (RCT) involving a total of 558 smokers with PAD, found that smoking cessation programs did not significantly increase the overall likelihood of quitting smoking (risk ratio 1.48; 95% confidence interval 0.84–2.61). Consequently, it remains unclear whether a therapy specifically tailored to the needs of this patient group could significantly improve abstinence rates, making it both clinically and socio-economically relevant.

Aim of the ASCHR trial

The aim of the ASCHR trial is to scientifically evaluate the efficacy, practicability, acceptance and efficiency of a multi-stage cessation program based on the German guideline for smoking cessation in patients with PAD, compared to usual care. Most smoking cessation studies have involved volunteers interested in quitting smoking, whereas PAD patients are generally harder to persuade to stop smoking, as demonstrated by previous research [9]. This particular patient group presents unique challenges in terms of approach and motivation.

Furthermore, most acute hospitals in Germany do not offer specific smoking cessation programs for their patients. Telemedicine, as a means of remotely delivering healthcare through information and communication technology, provides an integrated care pathway that combines treatment for smoking-induced diseases with preventive measures supporting smoking cessation. In the ASCHR trial patients with PAD are informed about and enrolled in a multi-step smoking cessation program by their treating physician at one of 23 participating clinics for vascular surgery or angiology (hereafter referred to as treating clinics). The smoking cessation program itself is managed and delivered remotely by a central psychological clinic in Germany – (hereafter referred to as trial center).

The primary hypothesis is that the multi-stage cessation program will increase the proportion of PAD patients who successfully quit smoking by at least 10 percentage points immediately after the intervention compared to those receiving usual care.

The secondary hypothesis posits that the multi-stage cessation program will sustain this increased cessation rate by at least 10 percentage points at a 6-month follow-up compared to those receiving usual care.

Methods/design

The ASCHR trial is a multicenter, two-arm RCT with a parallel group design and a 1:1 allocation ratio. One group receives an eight-month multi-stage cessation program (intervention group), while the other group receives usual care (control group). Potential patients are recruited from 23 treating clinics located in the German federal states of North Rhine-Westphalia, Lower Saxony and Hamburg. After enrolment, the trial center handles randomization via an Interactive Web Response System (IWRS), stratified by treating clinics. Psychologists at the trial center then manage the delivery of the intervention and data collection.

Study population

Eligible patients have to be active smokers and must have undergone revascularization therapy for PAD stage II to IV according to Fontaine recently [17]. Inclusion criteria include ages 18 to 80 years, mental and physical capacity to fully understand the scope and consequences of the study and follow study instructions, and providing written informed consent.

Exclusion criteria include inability to consent, non-compliance, a lack of a device for video consultations (smartphone, notebook etc.) or lacking internet access, pregnancy and/or breastfeeding, chronic skin or respiratory disease, life expectancy of less than six months, medically relevant illness or treatment that could influence the evaluation of the study, and recent participation in another study within the last 30 days. Patients must also not be employed by or dependent on the trial’s sponsor, investigator, or their representatives.

Description of the intervention

Intervention group

Patients in the intervention group receive a newly developed eight-month multi-stage smoking cessation program based on the German guideline utilizing telemedicine. The program consists of four stages with multiple components, progressing based on the patient’s current smoking status at standardized defined intervals (Fig. 1). The program starts with individual smoking cessation counseling by trained psychologists via video consultation (stage 1, starting at T0).

Fig. 1
figure 1

Study schedule

Full size image

Smoking cessation counseling

Stage 1: Stage 1 involves cognitive-behavioral therapy (CBT) for smoking cessation based on the German guideline for smoking cessation, including motivational interviewing, psychoeducation to convey an understanding of the disease and cognitive restructuring to influence attitudes towards smoking and withdrawal symptoms. Counseling is carried out by trained psychologists via video consultation offered once per week and is designed to reach older patients with severe or chronic somatic disorders and functional limitations.

The counseling concept consists of three phases, each tailored to the patient’s individual needs and adherence. The transition to the next phase occurs only after the current phase is successfully completed. In the event of a relapse, the previous phase is repeated.

Intensive motivation of the patient to stop smoking

This phase focuses on developing the patient’s motivation to quit smoking. It involves relationship building, psychoeducation, and motivational interviewing. Counseling is based on four main processes: relationship building, focusing, evocation, and planning. Special attention is given to distinguishing between status-quo language and change language. Signs of dissonance in the counselor-patient relationship are recognized and addressed early. The conversation emphasizes cooperation and authentic compassion. Counselors are trained to recognize resistance and address it therapeutically by refraining from criticism. Responding calmly to patients’ defenses of their previous smoking behavior and focusing on future behavior strengthens their inner motivation to quit. In addition to motivational interviewing, a thorough biographical and addiction history is taken, and the individual background is explored. Whenever possible, the immediate environment, including relatives, is involved to discuss fears and concerns about tobacco consumption.

Preparation and support for smoking cessation

Motivational interviewing continues and expands in this phase, employing cognitive restructuring techniques, such as Socratic dialog, to address dysfunctional attitudes towards smoking. The focus is on identifying and challenging these attitudes, followed by individualized planning and implementation of smoking cessation. The aim is to develop alternative, helpful approaches. In addition, counselors encourage confidence in abstinence and provide practical training on managing critical smoking cravings. These measures enhance stimulus control and teach patients relaxation and withdrawal-specific symptom management techniques.

Stabilization of abstinence

Motivational interviewing continues in this phase, with an emphasis on developing an emergency plan for dealing with relapses covering both damage limitation and regaining confidence in abstinence. The difference between a lapse and a relapse is discussed. Long-term coping strategies, such as mindfulness-based approaches, are trained. Peer support is offered through direct exchange with other patients and connections to self-help groups. Special consideration is given to patients with comorbid mental illnesses.

Stage 2: Smoking cessation counseling + NRT.

After two months, patients are assessed (T1). If they have not quit smoking, NRT is offered as an addition to counseling, specifically, using nicotine patches in descending doses.

Stage 3: High-frequency smoking cessation counseling + continued NRT.

At four months, patients are assessed again (T2). If they have not quit smoking, the frequency of counseling increases to twice a week, and NRT continues with low-dose nicotine patches. If psychological counseling combined with NRT, is not sufficiently effective, the German guideline for smoking cessation typically recommends drug treatment as the next step. Originally, stage 3 included offering varenicline alongside individual smoking cessation counseling. However, neither varenicline nor bupropion, both of which have a grade A recommendation according to the guideline, are currently available. As a result, stage 3 has been adapted to exclude drug treatment, making a fully guideline compliant program unfeasible.

Stage 4: Smoking cessation counseling + ANDS.

At six months, patients are assessed again (T3). If they have not quit smoking, NRT is discontinued, and the use of ANDS, such as e-cigarette or tobacco heater (including consumables) is offered, based on shared-decision making.

Throughout the intervention, participants' smoking status is evaluated at two, four, and six months (i.e., T1, T2, T3). If they quit smoking, they continue receiving the components of their current stage. If they do not quit, they advance to the next stage. The program sequence varies among participants, with differences in stages applied allowing an individualized approach. The study schedule includes a maximum of 50 contacts in the intervention group (Table 1).

Table 1 Frequency of contacts in the intervention group
Full size table

Control group

During the first fourteen months after study inclusion, patients in the control group receive no explicit smoking cessation intervention. As with the intervention group, questionnaire data is collected at individual timepoints (i.e., T0, T1, T2, T3, T4, T5, T6). Additionally, during these remote contacts every two months (i.e., T0, T1, T2, T3, T4) patients are encouraged to stop smoking. They are informed about the health risks of smoking and benefits of quitting. At the beginning of the study, patients receive the brochure "I’m ready to quit smoking" from the Federal Center for Health Education. Following the waiting period of 14 months (T5, see Figs. 1 and 2), control group patients are offered a two month single-stage cessation intervention. Patients can choose between receiving NRT (patches with descending dose over time) or ANDS (e-cigarette or tobacco heater including consumables) for two months. If patients accept one of these offers, the responsible treating clinic arranges an in-person appointment to provide the chosen products. After two months, patients accepting and receiving the products are invited back to evaluate on smoking cessation (T6).

Fig. 2
figure 2

Overview of tests and systematic surveys used. Abbreviations: PHQ: Patient Health Questionnaire, WHOQL: World Health Organization Quality of Life-BREF, WMS: Wechsler Memory Scale, RWT: Regensburg Verbal Fluency Test, WST: Vocabulary Test, NEO-FFI: NEO Five Factor Inventory

Full size image

Endpoints

Primary endpoint:

The primary endpoint is the quit rate at the end of the intervention (T4, 8 months). We hypothesize that our multi-stage cessation program will achieve a smoking cessation rate of at least 25% in the intervention group, compared to typical cessation rates of 10–15%. An increase of the quit rate by at least 10 percentage points in the intervention group compared to the control group is considered a relevant change, corresponding to a number needed to treat (NNT) of ≤ 10.

Null hypothesis (H0): At T4 (end of the intervention), the proportion of patients with successful smoking cessation in the intervention group (pINT) is equal to that in the control group (pCON); H0: pINT = pCON.

Alternative hypothesis (H1): The proportion of patients with successful smoking cessation at T4 in the intervention group and the control group differ; H1: pINT ≠ pCON.

Secondary endpoints:

The secondary endpoint is the quit rate six months post-intervention (T5, 14 months) (see “data collection” for more information about the markers in question). The objective is to attain a sustained quit rate which is at least 10 percentage points higher in the intervention group compared to the control group. The statistical analyses will be identical to those testing the alternative hypothesis of the primary endpoint.

Another project objective is to delineate prognostic markers of successful smoking cessation using complex, multivariate, data-driven analysis methods.

Specific questions include:

Which markers predict premature drop-out?

Are there markers that correlate with successful cessation?

Are there markers that correlate with successful cessation through psychological counseling?

Are there markers that correlate with successful cessation through NRT?

Are there markers that correlate with successful cessation through ANDS?

Sample size calculation

To calculate sample size, we assume a typical quit rate of 15% (usual consultation) in the control group for the primary outcome variable "smoking cessation at the end of treatment" (T4) and consider a 10 percentage point increase as clinically relevant. In the stratified multi-center trial design, we postulate this difference is homogeneous across all centers, striving for a NNT of 10. To demonstrate 10 percentage point difference in cessation rates using a two-sided chi-square test at the 5% level with a power of 90%, a sample size of at least 516 per group is required. Assuming an approximate dropout rate of 35% in both groups, a total sample size of at least N = 1032 study patients is needed. With a total sample size of N = 1032, we will be able to adequately consider and compensate for the expected dropout. This means that at least 1032 patients will be included, of whom 35% (approximately N = 362) will drop out during the study, leaving N = 670 in total and n = 335 per group. With an 18-month recruitment period, this equates to roughly 60 patients monthly. After consultation with individual treating clinics, recruiting 2 to 3 patients per clinic per month is deemed feasible. Therefore, leading to 23 treating clinics.

Data collection

Data collection is identical in both groups with the intervention group receiving additional intervention-related data collection and the control group undergoing supplementary data collection at T6 to assess the two month single-stage cessation intervention (Fig. 2). Potential markers, including personality traits, age, gender, cognitive performance or specific parameters of smoking behavior, are documented at study inclusion (T0) and, at T1, T2, T3, T4, and T5.

  • Sociodemographic and clinical information

Demographic information (age, gender, education, occupation, relationship status) and clinical details (PAD stage, PAD therapy, comorbidities, medication, treating physician) are collected at T0.

  • Smoking behavior and symptoms of dependence and withdrawal

Patient-reported smoking behavior and symptoms of dependence and withdrawal are assessed from T0 to T5, with additional assessment at T6 for the control group. Parameters include current smoking status and, if applicable, partner’s consumption status (T0 only), pack years (T0 only), tobacco product/nicotine products used, extent of consumption, self-assessment of dependence, Fagerström Test for cigarette dependence, evaluation of previous quit attempts (T0 only), motivation to quit smoking (T0 only), weight gain, smoking-associated symptoms via the COPD Assessment Test (CAT) and withdrawal symptoms via the Mood and Physical Symptoms Scale (MPSS) (T1 to T6 in case of smoking cessation).

  • Cognitive functions, psychological wellbeing and quality of life

Cognitive functions, psychological symptoms, personality traits and quality of life are assessed using standardized tests at study inclusion (T0): Wechsler Memory Scale (WMS, short-term and working memory); Regensburg Verbal Fluency Test (RWT, executive functions); Vocabulary Test (WST, premorbid IQ); DemTect (dementia screening procedure); Patient Health Questionnaire (PHQ, mental disorders); NEO Five Factor Inventory (NEO-FFI, multidimensional personality inventory) and World Health Organization Quality of Life-BREF (WHOQOL-BREF, subjective quality of life).

  • Further intervention-related data

In each counseling session, data on current smoking status and current intervention stage, counseling phase and psychological methods used are collected (intervention group only). If additional products to support smoking cessation (NRT or ANDS) are offered at T1 to T3 to intervention group and at T5 to control group, data are collected on patient decision to accept or reject the offer.

  • Primary and secondary endpoint

Smoking cessation is verified via carbon monoxide levels in exhaled air at T4 (primary endpoints at 8 months) and T5 (secondary endpoint at 14 months), using the Smokerlyzer® Micro + ™ carbon monoxide breath test device (Bedfont Scientific, UK). A patient is considered a non-smoker if a carbon monoxide value of < 6 ppm is detected. Smoking cessation is coded dichotomously ("yes/no"), and the carbon monoxide value concentration is recorded as a continuous value.

  • Process evaluation

Process evaluation includes data on the fidelity of intervention delivery and patient and counselor satisfaction. Patient satisfaction is assessed via telemedicine acceptance evaluation at T4 and questionnaires at T1 to T5, focusing on problems and satisfaction with the process, counseling sessions, counselor, stages and the smoking cessation program as a whole. Counselor satisfaction is evaluated through a mixed-method approach, including documentation during/after telemedical counseling appointments and interviews at the end of the intervention phase.

Program process indicators are collected to identify deviations from program specifications (e. g., number of consultation appointments, sequence of individual interventions, time between product offer and issue). Additionally, counselors assess counseling appointments for participation, motivation, adherence, relationship quality and technical problems.

  • Evaluation of telemedicine acceptance

Within the ASCHR trial, user acceptance of the intervention’s telemedical components (provision of counseling via video consultations) is evaluated for both patients and counselors. Patients’ acceptance is captured via a standardized questionnaire developed based on the Unified Theory of Acceptance and Use of Technology for private usage contexts (UTAUT2) [18] and existing specific questionnaires and studies on telemedicine and video consultation acceptance. Patient data are collected at T4, while counsellors’ acceptance is captured through qualitative methods (semi-structured interviews) at the time of the last patient out.

  • Health economic evaluation

For health economic evaluation, data on resource consumptions necessary to determine intervention costs are collected. This includes the time required for intervention delivery by counselors and treating clinic staff, the number and type of products offered in stage 2 to 4, and overhead costs for videoconferencing software, staff training, and counselors’ office equipment. Data collection employs both quantitative and qualitative methods. Intervention costs are compared with efficacy as measured by primary and secondary endpoints (cost-effectiveness analysis). Additionally, data on short-term effects on patient-relevant outcomes (hospital admissions, their length and reasons, sick days, employment status, smoking-related data as outlined above) are collected for further comparisons.

Data analysis

All base line data, test procedures and other patient surveys are documented utilizing the digital research software REDCap. Some tests and surveys are conducted during video interviews, with psychologists reading out questions and recording the answers, which are subsequently entered into REDCap. Other tests are computerized and implemented as questionnaires in REDCap, permitting patients to complete them on-screen during video conferences, with the counselor remaining connected to provide guidance, or by themselves between two appointments.

The alternative hypothesis is tested using a stratified Cochrane Mantel Haenszel chi-square test at the two-sided 5% significance level. In the event of a significant effect, a sensitivity analysis with a Breslow Day test is conducted to ascertain whether the treatment differences vary among recruiting clinics. If the Breslow Day test yields significance, the results of the Cochrane Mantel Haenszel chi-square test must be questioned.

Quality control

Due to the central program component of remote psychological counseling, this trial cannot be blinded. Both psychological counselors and patients are aware of the group allocation. Given this open trial design, potential biases such as detection, attrition and performance may distort the study results. Allocation bias is mitigated through randomization following a systematic approach [19]. Furthermore, the primary endpoint is determined based on objectively measured CO concentration in the breath, as described above, to minimize potential detection bias.

Conclusion and outlook

The ASCHR trial addresses the challenging task of smoking cessation in patients with PAD, which is necessary yet rigorous to accomplish. The study aims to determine whether employing all available support tools outlined in the German guideline for smoking cessation (such as counseling, NRT or, if necessary, ANDS) within a multi-stage telemedicine program enhances smoking cessation rates in patients requiring intervention or surgery due to PAD compared to usual care. Remote counseling forms a core element of the study, facilitating patient-centered psychotherapeutic counseling aimed at smoking cessation. While psychological/psychotherapeutic counseling and therapy represent the gold standard for addressing other addictions, they remain inadequately available for smoking cessation counseling. Success in this study may imply similar potential for such a program in other patient cohorts, including those with incipient PAD, coronary heart disease, or early smoking-related lung disease. Moreover, such an approach could effectively promote smoking cessation in patients with smoking-related tumors and their precursors. While providing effective smoking cessation measures for patients is crucial, it is vital to identify and offer successful interventions supporting cigarette abstinence to all smokers before the onset of smoking-related diseases. If the trial yields significant positive effects, efforts should be directed towards implementing the program into routine care in Germany, with subsequent scientific investigation into its efficacy, feasibility, acceptance, and efficiency across various target groups.