Rationale and design of WEBCARE: A randomized, controlled, web-based behavioral intervention trial in cardioverter-defibrillator patients to reduce anxiety and device concerns and enhance quality of life
© Pedersen et al; licensee BioMed Central Ltd. 2009
Received: 6 June 2009
Accepted: 23 December 2009
Published: 23 December 2009
The implantable cardioverter defibrillator (ICD) is generally well accepted, but 25-33% of patients experience clinical levels of anxiety, depression, and impaired quality of life (QoL) following implantation. Few trials in ICD patients have investigated whether behavioral intervention may mitigate the development of these adjustment problems. We present the rationale and study design of the WEB-based distress management program for implantable CAR dioverter dE fibrillator patients (WEBCARE) trial.
WEBCARE is a multi-center, multi-disciplinary, randomized, controlled behavioral intervention trial designed to examine the effectiveness of a web-based approach in terms of reducing levels of anxiety and device concerns and enhancing QoL. Consecutive patients hospitalized for the implantation of an ICD will be approached for study participation while in hospital and randomized to the intervention arm (n = 175) versus usual care (n = 175) at baseline (5-10 days post implantation). Patients will complete assessments of patient-centered outcomes at baseline, 14, 26, and 52 weeks after implantation. Patients randomized to the intervention arm will receive a 12-week web-based behavioral intervention starting 2 weeks after implantation. Primary endpoints include (ii) patient-centered outcomes (i.e., anxiety, depression, ICD acceptance, QoL); (iii) health care utilization; and (iiii) cost-effectiveness. All primary endpoints will be assessed with standardized and validated disease-specific or generic questionnaires. Secondary endpoints include (iii) cortisol awakening response; and (iiii) ventricular arrhythmias.
WEBCARE will show whether a behavioral intervention using a web-based approach is feasible and effective in reducing anxiety and ICD concerns and improving QoL in ICD patients.
http://www.ClinicalTrials.gov. Identifier: NCT00895700.
Implantable cardioverter defibrillator (ICD) therapy is considered the treatment of choice for the prevention of sudden cardiac death (SCD) both in patients who have survived life-threatening arrhythmias (secondary prevention) and in patients at risk for these arrhythmias due to coronary artery disease and left ventricular dysfunction (primary prevention) . The number of ICD implantations has risen considerably, since the first ICD was implanted in humans [2–4]. This increase in implantation rates can in part be attributed to expansion of the indications for ICD implantation to also include primary prevention, due to ICD therapy being superior to anti-arrhythmic drugs in the prevention of SCD in these high-risk patients [5–7].
Despite the medical benefits of ICD therapy, and the device generally being well accepted by the majority of patients , 25-33% of patients experience clinical levels of anxiety, depression, and impaired quality of life (QoL) following implantation [9–12]. These difficulties may be attributed to actual ICD shocks [13, 14], but also to device-related concerns including fear of shocks [15, 16], ICD advisories (i.e., a notification from ICD manufacturers that the hardware may potentially malfunction) , and the psychological make-up of the patient, including lack of optimism  and personality factors, such as the distressed (Type D) personality [11, 12, 19]. The prevention of the manifestation of psychological distress in ICD patients is important, given preliminary evidence that distress may increase the risk of ventricular tachyarrhythmias [20–22]. Hypercortisolemia, reflecting a dysregulation of the hypothalamus-pituitary-adrenocortical axis, may provide one of the mechanisms linking psychological factors to ventricular tachyarrythmias due to increased inflammation arising from chronic stress .
Preliminary evidence suggests that ICD patients benefit from psychological and behavioral intervention, with the largest effect being found in reductions of symptoms of anxiety and improved exercise capacity . One intervention trial has also found a reduction in cortisol levels . However, the number of large-scale intervention trials in ICD patients is scarce [24, 26], with the majority of these trials having used a nurse-based approach, cognitive behavioral therapy as stand-alone therapy, or in combination with cardiac rehabilitation. A web-based intervention may be equally effective and have advantages over these more traditional forms . Advantages of a web-based intervention include its low-threshold accessibility via the internet, which makes it logistically feasible for most patients to participate, as they do not have to take time off work, but can access the intervention at home in their own time. In addition, a web-based approach safeguards the patient's anonymity, and the patient avoids the stigma associated with traditional, face-to-face therapy. Such an approach may be particularly useful for patients with a Type D personality profile, who are at increased risk of adverse health outcomes, as they do not share their emotions in social interactions due to fear of rejection .
The WEB-based distress management program for implantable CAR dioverter dE fibrillator patients (WEBCARE) is a Dutch multi-center, multi-disciplinary, randomized, controlled behavioral intervention trial designed to examine the effectiveness and feasibility of a web-based approach in terms of reducing levels of anxiety and device concerns and enhancing QoL in ICD patients. The trial has been registered on http://www.ClinicalTrials.gov (NCT00895700).
Study population and eligibility criteria
Consecutive patients (N = 350) hospitalized for the implantation of an ICD in three medical centers in The Netherlands will be approached for study participation while in hospital and randomized to the intervention arm (n = 175) versus usual care (n = 175) at baseline (5-10 days post implantation). Patients (i) being implanted with an ICD, (ii) between 18-75 years of age, (iii) speaking and understanding Dutch, (iv) with access to and ability to use the internet, and (v) providing written informed consent will be eligible to participate. Patients with a life expectancy less than 1 year, with a history of psychiatric illness other than affective/anxiety disorders, on the waiting list for heart transplantation, or with insufficient knowledge of the Dutch language will be excluded.
Study procedure, randomization and follow-up
The study protocol will be approved by the medical ethics committees of the participating centers. The study will be conducted according to the Declaration of Helsinki, as amended in 2008 by the World Medical Association, and all patients will be informed orally and in writing about the purpose, rights, and possible benefits/risks of the study.
Primary endpoints include (ii) patient-centered outcomes (i.e., anxiety, depression, ICD acceptance, QoL); (iii) health care utilization; and (iiii) cost-effectiveness of the intervention. Secondary endpoints include (iii) cortisol awakening response; and (iiii) ventricular arrhythmias.
Assessment of primary endpoints
Patient-centered outcomes and psychological factors assessed in the trial
State Trait Anxiety Inventory (state only)
Florida Shock Anxiety Scale
Posttraumatic Stress Scale
Denollet Anxiety Inventory
Hospital Anxiety and Depression Scale
Patient Health Questionnaire
Quality of life
Short Form Health Survey 12
Minnesota Living With Heart Failure Questionnaire
ICD Patient Concerns Questionnaire
Florida Patient Acceptance Survey
Health care utilization and cost-effectiveness
Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness
Type D personality
Type D Scale
Assessment of secondary endpoints
Salivary cortisol will be assessed, using the Salivette (manufactured by Sarstedt, Etten-Leur, The Netherlands), at 3 out of the 4 time points, corresponding to the assessment of patient-centered outcomes and psychological variables (i.e., T0 = 5 to 10 days after ICD implantation; T1 = 14 weeks post-implantation; T3 = 52 weeks post-implantation). Due to test-retest reliability characteristics of cortisol [34, 35], samples will be taken on two consecutive weekdays at each time point. Four samples will be taken at each time point and on the consecutive day, that is (a) when waking up, (b) 1/2 hour later, (c) 11.00 a.m., and (d) 3.00 p.m. Samples will be sent to the coordinating trial center, where they will be stored at -20°Celsius until assayed.
Information on ventricular arrhythmias will be gathered from the electrograms stored by the ICD that will be reviewed and classified by two experienced electrophysiologists from the EP staff of the participating centers, who are blind to whether patients are assigned to the treatment or usual care arm. In case the two reviewers disagree about the diagnosis, a third one will be consulted to reach a consensus. For each episode, the date, type, and mean cycle length of the tachyarrhythmia will be recorded, as well as the type and outcome of delivered ICD therapy. The arrhythmia will be classified as (1) ventricular tachyarrhythmia or (2) atrial tachyarrhythmia without a coexistent ventricular arrhythmia. Therapy triggered by ventricular tachyarrhythmia will be considered as appropriate, while therapy delivered for atrial tachyarrhythmia (including atrial fibrillation, atrial flutter, atrial tachycardia, sinus tachycardia) or T wave oversensing and noise will be defined as inappropriate
Intervention versus usual care
Components of the 12-week web-based intervention
Topics dealt with
▪ Psycho-education about the ICD
▪ Emotional reactions to ICD therapy
▪ Problem-solving skills
▪ Which aspects of ICD therapy may lead to distress
▪ Cognitive restructuring
▪ How to deal with shocks
▪ Disease-specific issues and fears
▪ Relaxation training
▪ How to prevent the avoidance of activities
▪ Personalized feedback by a therapist via the computer
▪ Interpretation of bodily symptoms
▪ How to cope with uncertainty
▪ Help-seeking behaviour
▪ How to cope with stress
Statistical analysis and power calculation
The trial is designed to show whether a web-based behavioral intervention is effective in improving patient-centered outcomes compared to usual care. The power analysis was performed in relation to anxiety as the primary endpoint, since anxiety is a pertinent outcome measure in ICD patients due to the unique feature of the ICD being able to provide a shock. With (i) an expected between group effect size of .30., based on a recent meta-analysis of web-based intervention for symptoms of anxiety and depression  and taking into consideration that our population consists partly of patients with subclinical anxiety and depression levels; (ii) alpha = 0.05; (iii) power = 0.80 (two-sided test), 350 patients are needed (i.e., 175 in each condition). Although we had a response rate of 82% in an earlier study [16, 19], based on a more conservative response rate of 50%, 700 patients need to be approached.
The effectiveness of the intervention will be examined using the intention-to-treat principle, with the inclusion of all randomized participants in the statistical analysis regardless of whether they completed the intervention or the follow-up measurements. Missing data will be imputed using regression imputation techniques. Univariable and multivariable regression analyses (both linear and Cox proportional hazard regression analysis) and analysis of variance and analysis of covariance with repeated measures will be used to investigate the effect of the intervention on the endpoints. The type of regression analysis will depend on the endpoint in question. Demographic, clinical and psychological variables will be included in multivariable analyses in order to control for their potential confounding effects. A p-value < 0.05 will be used to indicate statistical significance. All data will be analyzed using SPSS 17.0 for Windows (SPSS Inc., Chicago, Illinois).
Preliminary evidence suggests that psychological and behavioral intervention may mitigate the development of adjustment problems in ICD patients, but the number of large-scale intervention trials in ICD patients is scarce [25–27]. In addition, all of these trials have used a nurse-based approach, cognitive behavioral therapy as stand-alone therapy, or in combination with cardiac rehabilitation. A web-based intervention may be equally effective and have advantages over these more traditional forms . The WEB-based distress management program for implantable CAR dioverter dE fibrillator patients (WEBCARE) is a multi-center, multi-disciplinary, randomized, controlled behavioral intervention trial designed to examine whether a web-based approach leads to better patient-centered outcomes, in terms of reduced levels of anxiety and device concerns and improved QoL. The trial aims to include 350 patients from three Dutch centers.
Implantable cardioverter defibrillator
Quality of life
Sudden cardiac death.
This trial is supported with grant no. 300020002 from ZonMw - The Netherlands Organisation for Health Research and Development, the Hague, The Netherlands. We would like to thank Peter Zaadstra from STIN (Stichting ICD dragers Nederland - Association for Dutch ICD patients) for his willingness to serve as consultant on the trial.
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