Study design
EROSIVE OESOPHAGITIS
VISION is a 5-year, randomised, open-label, parallel-group, multicentre, phase 4 study conducted across 33 specialised medical institutions (university hospitals, general hospitals, and clinics; Additional file Patients with endoscopically confirmed erosive oesophagitis (LA Classification Grades A–D) at the start of treatment (week 0) were randomised in a 2:1 ratio to receive either vonoprazan 20 mg or lansoprazole 30 mg once daily for a healing phase of either 4 weeks (for patients with confirmed endoscopic healing of erosive oesophagitis at week 4) or 8 weeks (for patients with no confirmed endoscopic healing of erosive oesophagitis at week 4). Patients with endoscopically confirmed healed erosive oesophagitis at week 4 or 8 of the healing phase then entered a 260-week maintenance phase. Healed erosive oesophagitis was defined as the absence of an endoscopic mucosal break (Grade 0 according to severity classification of erosive oesophagitis). During the maintenance phase, patients in the vonoprazan group were administered a starting dose of vonoprazan 10 mg once daily, and patients in the lansoprazole group were administered a starting dose of lansoprazole 15 mg once daily, for up to 260 weeks (thus a total of up to 268 weeks of treatment). Vonoprazan and lansoprazole doses were increased to 20 mg and 30 mg, respectively, if initial doses were insufficient for maintenance treatment of erosive oesophagitis. Patients were randomised and allocated to treatment via a web registration system and were administered the study drugs by the principal investigator or investigator.During the healing phase, visits were planned at weeks 0 and 4, and also at week 8 for patients with no endoscopic healing of erosive oesophagitis at week 4. During the maintenance phase, an initial visit took place on initiation of maintenance treatment followed by visits every 12 weeks up to week 108 and visits every 24 weeks up to week 228, with a final visit at week 260.For a uniform evaluation process of endoscopic images, a standard operating procedure for the evaluation was established. A start-up meeting at each site and two seminars for all investigators were held to thoroughly inform the standard operating procedures. The delegated investigator at each study site conducted and evaluated the endoscopy. Throughout the study period, the same investigator was preferred to conduct and evaluate the endoscopy as far as possible for each patient.This study is being and has been conducted in accordance with the Declaration of Helsinki Ethical Guidelines for Clinical Research, Clinical Trials Act (since 1 April 2018), and all applicable laws and regulations, including, without limitation, data privacy laws and conflict of interest guidelines. Before the enactment of the Clinical Trials Act, this study was conducted in accordance with the Ethical Guidelines on Biomedical Research Involving Human Subjects (the Ministry of Education, Culture, Sports, Science and Technology [MEXT] and the Ministry of Health, Labour and Welfare [MHLW], 22 December 2014; this guideline has since been renamed the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects). Owing to the enforcement of the Clinical Trials Act in Japan on 1 April 2018, VISION was classified as a ‘Specified Clinical Trial’ on 21 November 2018. The transformation review was conducted at ‘Certified Review Board of National Center for Global Health and Medicine’ (CRB3180021) certified by MHLW, and after that the study was approved and registered under the trial ID jRCTs031180040. Prior to this classification, the study was reviewed by the Ethical Review Boards of each study site, and informed written consent was obtained from all study participants. All authors have checked the study data and reviewed and approved the final manuscript. The study has been registered with ClinicalTrials.gov (NCT02679508, registration date 10/02/2016), JapicCTI-163153, and the Japan Registry of Clinical Trials (jRCTs031180040).