This single-center, prospective, randomized controlled clinical trial was conducted at the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China, from September 2021 to December 2022. The inclusion criteria were (a) age, 18–70 years, (b) H. pylori infection confirmed by the 13 C-urea breath test (UBT), and (c) primary treatment. The exclusion criteria were (a) unfamiliarity with smartphones, (b) allergy to the treatment drugs, (c) treatment with antibiotics, colloidal bismuth pectin, H2 receptor inhibitors, or proton pump inhibitors within the previous 4 weeks, (d) serious concurrent diseases, (e) gastrectomy, and (f) pregnancy/lactation. Eligible patients were enrolled after they provided informed consent. The study protocol and informed consent form were approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University (2021-SR-583). The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2000029021).

Patients were randomized to the DTD or outpatient education (OE) group. Patients in both groups were treated with bismuth-containing quadruple therapy, consisting of esomeprazole 20 mg (Cspc Ouyi Pharmaceutical, Hebei, China), colloidal bismuth pectin capsule 200 mg (Zhendong Anxin Biological Pharmaceutical, Shanxi, China), amoxicillin 1000 mg (Lunan Pharmaceutical, Shandong, China), and clarithromycin 500 mg (Hengrui Pharmaceutical, Jiangsu, China), twice daily for 14 days. In the outpatient clinic, physicians collected the following information: gender, age, body mass index, education, history of smoking/drinking, symptoms before treatment, comorbidity, family history of gastric cancer, lifestyle habits (e.g., washing hands before meals, sharing a toothbrush cup), and knowledge about H. pylori infection. To assess patients’ knowledge, the physicians recorded the patients’ answers to the following: Do you know if H. pylori is contagious? How many kinds of medication are used to treat H. pylori? How long does it take to treat H. pylori infection? When should the UBT be rechecked after H. pylori treatment?

All patients received routine outpatient instruction, including verbal and written education. Patients were informed of the importance of H. pylori eradication; the dosage, frequency, and adverse effects of the medications; and the review UBT date, and instructed to start taking anti-H. pylori drugs from the next day. A uniform instruction manual with notes for the treatment plan and the review UBT date was provided. This manual included the following information: (a) The drugs in the regimen are taken twice a day, and the dose cannot be missed. Esomeprazole and colloidal bismuth pectin must be taken 30 min before breakfast and dinner; the 2 antibiotics must be taken 30 min after breakfast and dinner. (b) The regimen duration is 14 days; treatment interruption should be avoided. (c) Possible adverse reactions include black stools and diarrhea. (d) Alcohol consumption is prohibited during treatment. (e) Follow-up 13 C-UBT is required to assess the presence of H. pylori infection, at least 1 month after the 14-day treatment regimen has finished. The physician confirmed with the patients if they understood the above information and provided further explanation if required.

The DTD model was integrated into an official service account of the WeChat platform. After following the account, the enrolled patients logged into the model during their treatment (Supplementary Fig. 1). DTD-group patients underwent DTD management as follows: (a) The patient clicked the “Start medication” button when starting the treatment plan, and the model began recording the treatment process. (b) Once the patient took all the day’s medications, he/she clicked the “Finish taking medication” button, and the model recorded the completion of the day’s treatment and displayed a success message. (c) Dates on which medications were taken were displayed in blue with a checkmark symbol; otherwise, they were displayed in gray. (d) Patients repeated the above process from day 1 to day 14. (e) When the day-14 recording was completed, the model automatically displayed the re-examination time (1 month after the end of the treatment; Fig. 1, Supplementary Fig. 2).

Schematic diagram of the usage instructions for the day-to-day management model

The OE group was not provided with DTD management. On the 14th day of taking medicines, the patients received a telephone call to inquire about the remaining dosages. Two months after treatment completion, the patients were again called to inquire about the review UBT results and to remind patients who had not undergone review UBT. To get as much data as possible to calculate the eradication rate, we again called the patients before the end of the study, and asked about the review UBT results.

The primary endpoints were medication compliance and follow-up compliance. The secondary endpoint was the H. pylori eradication rate. Good medication compliance was defined as taking > 80% of prescribed medications, calculated based on remaining dosages. Follow-up compliance was assessed by recording the review UBT date and calculating the number of days between treatment completion and review UBT (termed “review UBT time”). Completion of the review UBT within 1–2 months after treatment completion was classified as good follow-up compliance. A 13 C-UBT value < 4‰ indicated successful H. pylori eradication. Treatment-related AEs were also assessed using a standardized questionnaire.

A study reported a follow-up rate of 93.8% in their WeChat intervention group, as compared with 77.6% in their control group (P < 0.001) [14]. Assuming an α-error < 0.05, a β-error < 0.1, and a 20% dropout rate, we calculated that at least 122 patients per group would be needed.

Data were analyzed using SPSS v26.0. All intention-to‐treat (ITT), modified ITT (MITT), and per-protocol (PP) analyses were performed using the primary and secondary endpoints. In the ITT and MITT analyses, patients with missing data due to exclusion were considered to have failed eradication, poor medication compliance, and poor follow-up compliance. For patients without review UBT, the date of review was defined as February 28, 2023. Continuous variables were presented as median (interquartile range) and analyzed using the Wilcoxon rank-sum test; categorical variables were presented as frequency (percentage) and analyzed using the chi-square or Fisher’s exact test. P < 0.05 indicated statistical significance.