The ongoing GUIDEME study is a multi-center randomized controlled trial of an automated mobile phone miniprogram-based intervention with 6 months of follow-up. We hypothesize that education and medication reminder for patients can help reduction of A1c over 6 months. This RCT was registered at http://www.clinicaltrials.gov (NCT 04192409). The central ethics committee of Fuwai Hospital approved the study (No.2019-1151, June 2019). The recruitment and the last follow-up are expected to finish in June 2022 and December 2022, respectively. All participants provided written informed consent at the initial trial visit.
Patient and public involvement
No patient involved.
Inclusion and exclusion criteria
Patients must meet all of the following criteria to be recruited for the study: 1) Type 2 diabetes diagnosed by a physician prior to study enrollment; 2) documented coronary artery disease and isolated coronary artery bypass is recommended and performed; 3) access to a mobile phone with Wechat and ability to operate on the miniprogram. Patients are excluded if they could not read the materials, had cognitive or communication disorders, unable to provide informed consent or die before discharge.
We identify patients in the surgical ward who have been hospitalized with CHD and DM and who have undergone coronary artery bypass. The diagnoses of CHD and DM and the indication for surgical revascularization are adjudicated centrally, based on reviews of the patients’ medical charts. Once identified, study staff explained the study face-to-face and that they may be eligible to participate. A ‘screening log’ of basic demographic information and reasons for not participating in patients deemed ineligible or declined to participate has been recorded. Individual patient signature informed consent is obtained by the China National for Cardiovascular Disease independent of clinical office involvement.
Based on previous experience8, we estimated that surgical practice would provide an average of 1300 patients with CHD and DM undergoing CABG in Beijing Fuwai Hospital annually and 100 patients in Qingdao Fuwai Hospital.
Randomisation and blinding
Participants were randomly allocated to enter the intervention or the control arm in a 1:1 ratio using a computerized randomization system. In order to achieve a balance of participants’ characteristics in both arms, a stratified randomization approach is employed, based on age, gender, education degree, acute myocardial infarction history and medical insurance type. Statisticians and clinic staff are blinded to treatment allocation.
The interventions are education and reminder system for patients with CHD and DM, using mobile phone to allow transmission (Figure 1). Participants in the intervention groups receive video (including lines) about CHD and diabetes risk modification education for 6 months as well as the standard treatment. The control group receive standard treatment without risk factor modification support. All patients in the intervention groups receive the study treatment mobile phone mini-program software which is anchored in Wechat (Figure 2). A training session is held by the research staff on enrollment that participants in the intervention group are registered in the system so that they have access to the web-based individual patient portal and they are capable of receiving and reading system-driven coaching video material. In addition, participants in the intervention receive medication regimen reminder. Prior to commencement, the system is tested to confirm functioning effectively. Researchers at the China National for Cardiovascular Disease could monitor the visiting frequency of the system. Participants are also informed that they could withdraw from the study by sending text messages to the research staff. Outbound patient phone calls by the research staff are discouraged.
A cluster of 180 videos were developed by a multidisciplinary team of cardiac surgeons, cardiologists, endocrinologists, psychologists, nurses and public health researchers using a two-phase systemic and iterative approach. Coaching videos cover a range of secondary prevention after coronary artery bypass graft surgery in addition to diabetes self-management topics based on current guidelines19–13 including: (1) general education on CHD and DM, (2) postoperative antiplatelet agents; (3) lipid-lowering therapy; (4) b-Blocker Therapy; (5) glucose monitoring and control, (6) blood pressure control, (7) smoking cessation; (8) cardiac rehabilitation; (9) lifestyle recommendations such as weight loss, physical activity, diet. Other self-care behaviors including monitoring, self-management problem solving, reducing risks and healthy coping are considered as essential bahaviors for improving diabetes mellitus self-management and incorporated into video development accordingly1415. All videos are in Chinese and are less than 2 minutes. The captions of the videos are affiliated and are also developed into text.
Phase I: Developing videos
Lines of the coaching videos were originally drafted in Chinese based on current guidelines. BCTs were employed to develop short videos including goal setting, providing information on consequences of behavior, self-monitoring, barrier identification and social support1617. Table 1 illustrates the BCTs used in the lines of short videos. Videos were developed in form of lectures or dialogues in order to make them more acceptable to patients and compatible with Chinese beliefs and values18. Lectures began with a question regarding to the subject and are followed by the response. Videos of dialogue were made in the setting of real-world examples instead of abstract theories19. These videos were sent to experts in BCTs and subsequently reviewed, criticized and revised within the research team.
Behaviour change technique used in video development
Behavior change technique
Examples lines of video in English
Provide information about behaviour-health risk
General information about behavioural risk
Aspirin should be continued indefinitely to reduce graft occlusion and adverse cardiac events. In order to convey the most benefit of CABG to you, taking medications regularly.
Tell the person how to perform a behavior and/or preparatory behaviors
Smoking cessation is critical. Electronic cigarettes (e-cigarettes) have not been demonstrated to improve cessation rates and important concerns has been raised about their potential for adverse health effects. However, nicotine replacement therapy, such as bupropion and varenicline as adjuncts to smoking cessation for stable CABG patients after discharge is reasonable. And you can try this method!
Prompt barrier identification
Identify barriers to perform the behavior and plan ways of overcoming them
b-blockers are often associated with side effects such as weight gain, fatigue, and sexual dysfunction. You may feel upset about this and are reluctant to take it regularly. But if you have hypertention, a history of myocardial infarction or a history of heart failure, keep taking it regularly as this is good for your body. We will remind you to take this medication through mini-program. And you can also set a repeating alarm on your cellphone.
Prompt self-monitoring of behavior
The person is asked to keep a record of specified behavior
Meals, exercise, cold and diarrhoea will make your blood sugar levels fluctuate. Thus, you should perform self-monitoring of blood glucose (SMBG) prior to meals and snacks, at bedtime, occasionally postprandially, prior to exercise and prior to critical tasks such as driving. You may as well upload this data through the mini-program. In addition, perform the A1C test three months and six months after surgery even if you have stable glycemic control. Striving to achieve an HbA1c is a reasonable goal for most patients after CABG.
Set graded tasks
Set easy tasks, and increase difficulty until target behavior is reached
Have you ever felt hard to take medicine regularly? All things are difficult before they are easy. However, our mini-program system will help you. You can enter your medication and the system will automatically generate the ratings according to your medication adherence performance. More star you get, more benefit you will gain. Move on to get the most stars and it will make a great difference in the future!
Plan social support or social change
Prompt consideration of how others could change their behavior to offer the person help or (instrumental) social support
Symptoms of hypoglycemia include, but are not limited to shakiness, irritability, confusion, tachycardia, and hunger. Tell your friends and family when you have the symptoms above so that they give you the glucose (15-20g). Fifteen minutes after treatment, if SMBG shows continued hypoglycemia, the treatment should be repeated. Once SMBG returns to normal, the individual should consume a meal or snack. The family members should know where the glucagon is and how to administer it in case of blood glucose <54 mg/dL.
May involve a variety of specific techniques (eg. Progressive relaxation) that do not target the behavior but seek to reduce anxiety and stress
Relaxation is something we need to learn and practice. Listening to music, reading or talking to friends and family can ease stress.
Prompt the person to provide self-motivating statements and evaluations of their own behaviors to minimize resistance to change
Does your A1C decrease in value three months after CABG? If so, it is something worth celebrating. We are sure that you have put a lot of effort into taking medications and lifestyle modification. Keep up the good work and you can make a difference. If A1C remains less than 7%, it is supposed that you achieve the target of glycemic control. However, less stringent A1C goals (such as <8%) may be appropriate according to recent guidelines. Thus, glycemic target must be individualized to the needs of each patient and his or her disease factor.
Phase II: Expert review
The 180 videos were reviewed with a different focus by an expert panel consisting of clinicians and academics in the field of cardiology, endocrinology, epidemiology, psychology and linguistics. First, the clarity, accuracy and feasibility of each video was checked and verified. Second, linguists reviewed all videos and focus on the acceptability and readability of the video education material. Issues regarding to videos were addressed and the corresponding education videos were shoot again in order to achieve the desired target which the expert panel had proposed.
Frequency and timing of education video delivery
180 coaching videos in total were push forward to the participants in the intervention group across a 6-month timeframe. The videos were sent to the participant portal every 2 days in the morning. The theme of coaching video covers a range of recommendations from the recent guidelines. Participants in the intervention group will receive the update text message and log into the Wechat-based miniprogram to read the updated educational video material. Initially, only one education video is available. To evaluate the engagement in the miniprogram system, participants are required to finish the question at the end of every video, “Do you think that the information is easy to understand? Do you think that information is useful?”. The logbook data are analyzed at the completion of the study intervention. Through the 6-month follow-up, research staff call participants if they do not finish the questions for two consecutive weeks and only one call is made per patient during the intervention period, so as not to confound the intervention. Patient communication is delivered by automated feedback on the mobile phone Wechat-affiliated miniprogram and messaging through the message center in the patient web portal.
Data collection and management
Patient characteristics are collected from self-reported interviews with trained research staff and medical chart reviews including basic information, baseline clinical variables, biochemistry information, coronary angiography, echocardiographic outcomes, diabetes-related variables, surgical details, postoperative complication and socioeconomic status (Supplementary materials).
Additional assessments of baseline medication adherence, health status (EuroQol five-dimensional questionnaire: EQ-5D) are also conducted in person20. Biochemistry test will be analysed at the central laboratory. The process of recruitment is monitored and data collection is checked by trained staff from China National for Cardiovascular Disease to improve the quality control.
A specialized software platform was established by the Information Technology team for use in sending coaching video materials to participants and also recording responses. In addition, project progress can be supervised and 24-hour management support is provided through this web-based platform. Predesigned onscreen case report form is entered by two staff members independently, and data are then securely transmitted to the central server through automatic electronic transfer. Continuous checks are run to ensure that data being entered are complete and meet predefined data formats and ranges to ensure the reliability and validity of the data. The database is regularly backed up and password protected so that only a limited number of approved staff members can access the data. Data confidentiality policies of NCCD on data collection, storage and analysis have been strictly imposed to ensure the confidentiality.
The primary outcome is the change in glycaemic HbA1c by the central blood sample. Secondary outcomes include blood pressure, blood glucose, low density lipoprotein, a change in proportion of patients achieving HbA1c<7% of patients, graft patency, major adverse cerebrovascular and cardiovascular events (MACCEs), change in medication adherence, mini-program behavior adherence, changes in antihyperglycemic medications during the intervention and health status (EQ-5D). MACCEs include death, non-fatal myocardial infarction, stroke and any repeated revascularization and cardiac rehospitalizations. HbA1c is determined using a high-performance liquid chromatography technique with ADAMS A1cHA-8180 (ARKRAY, Japan). Graft outcomes are assessed by multislice computed tomographic angiography (MSCTA) or catheter coronary angiogram (CAB) at 6 months after coronary artery bypass grafting. The examinations are conducted according to standardized radiology and cardiology procedures. Digital images from a ≥64-slice CT scanner are analyzed with software (Intellispace portal Version 6.0, Phillips Healthcare). Members of the independent Image Data Review Centre reviewed the images and adjudicated the patency of the grafts blinded to treatment assignments.
Graft patency is defined according to FitzGibbon criteria21. In our trial, graft patency is defined as FitzGibbon grade A22 23. Quality of life is measured using the short version of EQ-5D.
The institutional follow-up protocol requires that patients who are discharged alive visit our outpatient clinic three and six months after coronary artery bypass graft. If adverse events are reported, the patient medical records in the outpatient clinic were checked cautiously. When the patients visited another hospital, they are asked to send copies of their medical records by mail. If the patient dies at home without any evidentiary material, a structured summary of death conversation with family members would be reported. All information is sent to NCCD for central adjudication according to prespecified criteria by trained clinicians.
All analysis will be conducted according to the intention-to-treat principle. Baseline patient characteristics are represented as the means with standard deviations (SDs) for continuous variables and proportions for categorical variables. The primary analysis used analysis of covariance. For categorical secondary outcomes, log-binomial regression is used to compare groups and calculate relative risk of outcomes at 6 months (ie, proportions of patients achieving HbA1c<7.0%). A generalized estimating equation model including terms for treatment is used to estimate between-group difference in graft patency and 95% confidence intervals (CIs). For the (time-to-event) secondary outcomes, hazard ratios (HRs) and corresponding 95% CIs are determined with Cox proportional hazards regression analysis. Kaplan-Meier curves are used to depict the occurrence of secondary outcomes over time. Follow-up of event-free patients with incomplete follow-up will be censored at the last clinical contact. Additionally, we performed prespecified subgroup analyses of outcomes by age (<60 and ≥ years), sex (male and female), area (urban and rural), education (≤12 and >12 years) and tertile of baseline HbA1c. Subgroup results are presented as mean differences with 95% CIs. All tests of significance are 2 tailed, with an a of 0.05.
We estimate that a sample size of 820 would provide 80% power at the 5% significance level to detect a 0.3% absolute difference in HbA1c change in the intervention group at 6 months, compared with the control group, assuming a mean HbA1c level of 7.0% at baseline (SD 1.4%) based on data from studies involving similar populations24, using PASS, version 11.0 (NCSS, Kaysville, UT), for sample size calculation. This sample size allowed for a 20% loss to follow-up during the study period. We used the SPIRIT checklist when writing our report25.