Application of a WeChat-based mini-app as a patient reminder in Helicobacter pylori eradication: a prospective multi-center randomized controlled study

Helicobacter pylori (H. pylori) is a major human pathogen related to a variety of diseases from chronic gastritis, peptic ulcer disease, gastric atrophy, to malignancies like gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma [1]. According to studies, approximately 4.4 billion individuals were infected with H. pylori worldwide, comprising half the world population [2]. In China, H. pylori infection also remains a major public health concern. A meta-analysis published in 2017 estimated the prevalence of H. pylori infection in China to be 55.8% (95%CI: 51.8–59.9%) [3]. With no effective vaccines currently available, most infections will persist for a lifetime without treatment [4, 5].

Despite previous controversies, recent consensus suggests that all patients without competing considerations should be offered eradication therapies. Likewise, all patients who have received eradication therapies should be assessed with the treatment outcome, preferably via non-invasive methods [6]. In China, current guidelines suggest bismuth-containing quadruple therapy (PPI + bismuth + 2 antibiotics) as the main empirical therapy for H. pylori eradication, with a treatment duration of 10–14 days [7]. The present recommended regimens in China have eradication rates of over 90% [8‐11]. These therapies, however, are complex and time-consuming, resulting in poor patient compliance. To improve compliance, physicians attempted traditional methods like pillboxes and medication calendars [12, 13]. In recent years, several researchers investigated the effects of short-message and telephone-based reminding systems on H. pylori eradication and patient compliance [14, 15]. However, the outcomes varied among different studies and sometimes contradicted each other. Thus, a prospective, multicenter study is necessary for further investigation.

As medication compliance is crucial in treating H. pylori infection, researchers have utilized a variety of methods to improve compliance, which showed inconsistent results. A single-center clinical trial in 2015 showed that a daily telephone-based re-education system slightly but not significantly improved patient compliance (84.3% vs. 74.3%, p = 0.069) while the eradication rates were similar between the two groups (PP analysis: 62.7% vs. 71.2%, p = 0.230) [15]. Another study in 2018 showed that a twice-daily short-message-based re-education system increased the H. pylori eradication rate (PP analysis: 82.1% vs. 73.4%, p = 0.078) and the eradication rate was significantly higher in patients below 40 years old (PP analysis: 88.6% vs. 71.2%, p = 0.036) [14].

Apart from the telephone- and short-message-based programs, WeChat-based methods also showed promising potentials in improving patient compliance. WeChat is a multi-purpose instant messaging, social media, and mobile payment app developed by Tencent. By 2020, WeChat has over 1.2 billion active users, often referred to as a super-app or an app-for-everything [19]. In 2015, a prospective, multi-center study showed that using WeChat, physicians could increase the quality of patient bowel preparation. With interactive instructions delivered through WeChat, more patients attained adequate bowel preparation and lower mean total and segmental Ottawa scores [20]. Another study also showed that WeChat-based notification on the first and fourteenth days significantly improved disease-related knowledge, medication adherence, and H. pylori eradication rates [16]. In 2017 WeChat introduced a new feature called “mini-programs” or “mini-apps”, which allows program developers to create more basic, simplified versions of apps stored and run within WeChat. By scanning the QR code, patients can download and install the mini-apps within seconds. The development of the mini-app offered physicians a handy option to improve patient compliance.

Increasing antibiotic resistance has become the main reason for decreased eradication rates in recent years [3, 21]. Apart from that, poor patient adherence due to adverse events, forgetfulness, or inadequate understanding of the disease also compromises treatment outcomes [22]. In this study, the mini-app significantly improved patients’ adherence, and the adverse event rate was slightly lower in the DMN group than in the control group (36.96% vs. 40.95%) but the difference was not statistically significant. Despite increased compliance, the eradication rate was not significantly improved in the DMN group. Whether patient adherence affects the ultimate eradication rate remains controversial. Some studies showed that the H. pylori eradication rate would increase as a result of better patient education and compliance while some others indicated that > 60% compliance might be sufficient for H. pylori eradication and further improvement had no significant influence on the H. pylori eradication rates [21, 23, 24]. The causality among patient education, medication compliance, and clinical benefits is still worth exploring. Besides, although the study failed to demonstrate a significant improvement in the overall H. pylori eradication rate, patient satisfaction score was significantly higher in the DMN group, and the vast majority of patients in the DMN group believed that the mini-app helped remind them to take the medications and provided reassurance.

This study has several limitations. First, some baseline characteristics of the patients, including the history of antibiotic use and whether they lived alone or with others, were not collected. The difference of basic characteristics between the two groups might affect the eradication rate of the H. pylori. Second, the compliance was calculated based on the pill-counting method, which was inevitably influenced by self-report bias. Patients might forget or intentionally conceal missed dosages due to embarrassment, causing overestimation of the compliance rate. In order to reduce self-report bias, researchers encouraged patients to bring all the remaining drugs and explained to them that drug leakage was normal rather than anything to be ashamed of. Third, the follow-up rates in the DMN group and the control group were 93.2% and 91.1% respectively, and the patients lost to follow-up shared similar baseline characteristics to those included in the PP analysis, which were generally believed to be acceptable and would not cause severe distortion to the study outcomes [25, 26]. Forth, the mini-app only supported one radical cure scheme among initial treatment patients. Considering its significant impact on patient compliance, it will be applied to other treatment schemes for both initial and refractory treatment choices in future work. In addition, there might be a selection bias as the current inclusion criteria excluded illiterate patients and patients who cannot use mini-app, which unfortunately limited the general application of the mini-app. App-aided education may be achieved with the help of close relatives who were capable of using app, which will be improved in the following study.

Our study showed that a mini-app-based notification system helped to improve patient adherence and satisfaction in H. pylori eradication, though no significant improvement was observed in the eradication rate or adverse event rate. The system provided a more efficient and flexible approach to improving patient compliance during H. pylori treatment in the future.