Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux.

OBJECTIVES: Objectively diagnosing non-erosive reflux disease (NERD) is still a challenge. We aimed to evaluate the use of in-vivo confocal laser endomicroscopy (CLE) to examine the microalterations of the esophagus in patients with NERD and its relationship with reflux episodes monitored by multiple intraluminal impedance-pH (MII-pH). METHODS: Patients with gastroesophageal reflux symptoms completed reflux disease questionnaires. NERD was determined by negative gastroscopy. Patients without reflux symptoms were recruited as controls. Pilot clinical study was followed by prospective controlled blinded study. All subjects were examined by white-light mode of the endoscopy followed by the standard CLE mode and then MII-pH monitoring. The microalterations seen on CLE images and the correlation between CLE features and reflux episodes were evaluated, the correlation between CLE and transmission electron microscope (TEM) data was also analyzed. RESULTS: On CLE images, NERD patients had more intrapapillary capillary loops (IPCLs) per image than did controls (8.29 ± 3.52 vs. 5.69 ± 2.31, P=0.010), as well as the diameter of IPCLs (19.48 ± 3.13 vs. 15.87 ± 2.21 µm, P=0.041) and intercellular spaces of squamous cells (3.40 ± 0.82 vs. 1.90 ± 0.53 µm, P=0.042). The receiver operating characteristic analysis indicated that IPCLs number (optimal cutoff >6 per image, area under the curve (AUC) 0.722, 95% confidence interval (CI) 0.592-0.853, sensitivity 67.7%, specificity 71.6%), IPCLs diameter (optimal cutoff >17.2 µm, AUC 0.847, 95% CI 0.747-0.947, sensitivity 81%, specificity 76%), and the intercellular spaces of squamous cells (optimal cutoff >2.40 µm, AUC 0.935, 95% CI 0.875-0.995, sensitivity 85.7%, specificity 90.5%) diagnosed NERD with reasonable accuracy. Combined features of dilatation of intercellular space plus increased IPCLs provided 100% specificity in the diagnosis of NERD patients. The intercellular spaces of squamous cells observed on CLE were highly related to that on TEM findings (r=0.75, P<0.001). Multivariate progressive regression analysis showed that acidic reflux, especially in the supine position, was related to the increased number and dilation of IPCLs in the squamous epithelium (ß=0.063, t=2.895, P=0.038 and ß=0.156, t=1.023, P=0.04). CONCLUSIONS: CLE represents a useful and potentially significant improvement over standard endoscopy to examine the microalterations of the esophagus in vivo. Acidic reflux is responsible for the microalterations in the esophagus of patients with NERD.