Comparison of the Effectiveness and Adverse Effects of Phorize (Vonoprazan) Versus Pantoprazole in Controlling Symptoms of Non-Erosive Reflux Disease (NERD) and Clinical Improvement of Erosive Esophagitis (EE)

To compare the effectivenes and adverse effects of vonoprazan with pantoprazole in controlling symptoms of Non-Erosive Reflux Disease (NERD) and achieving clinical improvement in Erosive Esophagitis (EE).

The study is a randomized, double-blind, phase 3 clinical trial with 4 parallel intervention groups with a sample size of 730 patients. Sealed Envelope software was used for randomization.

Patients with NERD or EE will be enrolled in the study in selected medical centers in Tehran, Shiraz, Isfahan, Ahvaz, Mashhad, Tabriz, Rasht, and Sari, if eligible, and will be randomly assigned to one of the intervention groups using a randomized block design. This study will be conducted in a double-blind manner.

Inclusion Criteria: Diagnosis of NERD or EE confirmed by an experienced and active endoscopist within the past 6 months, Exclusion Criteria: History of failed treatment with proton pump inhibitors ,fundoplication, gastrectomy, Barrett’s esophagus, dysplasia, Peptic ulcer disease, Gastrointestinal bleeding

In the EE arm, the first intervention group will receive vonoprazan 20 milligrams (mg) once daily for 8 weeks and then vonoprazan 10 mg once daily for 16 weeks. The second intervention group will receive pantoprazole 40 mg once daily for 8 weeks and then pantoprazole 20 mg once daily for 16 weeks. In the NERD arm, the third intervention group will receive vonoprazan 10 mg once daily for 8 weeks. The fourth intervention group will receive pantoprazole 20 mg once daily for 8 weeks. Vonoprazan: Abidi (Phorize), Pantoprazole: Tehran Shimi (Pentomid)

Heartburn-free time (daytime and night time). Number of heartburn-free days during the study period. Percentage of participants without heartburn at the end of the study.

Sealed Envelope Ltd.2024 software was used. In the erosive esophagitis arm, a total of 438 patients were numbered. Randomization was performed in blocks of 4 in a 1:1 ratio by assigning 3-letter codes consisting of numbers and Latin letters to the patient numbers. Accordingly, half of the patients will receive venoprazan and the other half will receive pantoprazole. In the non-erosive reflux disease arm, a total of 292 patients were numbered. In blocks of 4 in a 1:1 ratio, randomization was performed by assigning 3-letter codes consisting of numbers and Latin letters to the patient numbers. Accordingly, half of the patients will receive venoprazan and the other half will receive pantoprazole. The list of codes assigned to each patient in both study arms is kept in separate Excel files only accessible to the epidemiologist and study executive director and will not be made available to the treatment centers or patients.

Patients will be informed that they will be given one of two gastroesophageal reflux disease treatments, pantoprazole or vonoprazan, and that the type of medication assigned will not be known until the end of the study. In both study arms, medications were packaged in unlabeled, sealed, single-color bottles. The required medication bottles were placed in identical paper envelopes. The patient number and assigned randomization code were affixed to the bottle and the paper envelope. According to the instructions sent to the patient admission centers, in both study arms, patient admission will be done by number and in order. Therefore, patients and admission centers are blinded to the assigned medication.