Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study.

Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results: 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion: Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.

Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. METHODS: A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. RESULTS: Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. DISCUSSION: Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

The Disease Spectrum and Natural History of Patients With Abdominal Bloating or Distension: A Longitudinal Study.

Background/Aims: Abdominal bloating or distension (AB/D) is a common complaint in the outpatient of gastroenterology department. Since the potential contributors are numerous and complex, a longitudinal study on the disease spectrum and natural history of patients was performed to better understand the key factors of AB/D. Methods: Consecutive patients with the chief complaint of AB/D referred to the outpatient clinic were screened. Functional gastrointestinal disorders (FGIDs) were diagnosed according to Rome IV criteria. A 3-year follow-up was performed to seek for the changes in symptoms as well as disease spectrum. Results: A total of 261 participants were enrolled and 139 completed the follow-up. Most patients suffered from moderate to severe symptoms more than 1 day per week. Common causes of AB/D were FGIDs (51.7%) and organic diseases (17.2%). The latter group was older with lower body mass index (BMI). Functional dyspepsia was the most common type of FGIDs in AB/D. The symptoms of 18.0% of participants failed to improve at the end of the 3-year follow-up, and those diagnosed with FGIDs were most likely to continue to suffer. Abdominal pain was a positive predictive factor for good prognosis in the FGIDs group. Besides, only 22.7% of participants had a consistent diagnosis of FGIDs during follow-up. Conclusions: FGIDs are the most common diagnosis in patients with AB/D. Symptoms were especially hard to be improved. Classification diagnoses of FGIDs in AB/D patients fluctuated significantly over time.

A 39-Year-Old Man With Refractory Chronic Cough Accompanied by Regurgitation and Belching.

CASE PRESENTATION: A 39-year-old man who did not smoke was admitted to the hospital with recurrent cough for 1 year, accompanied by sputum expectoration (with a small amount of white phlegm), acid regurgitation, and belching. Nasal symptoms or other cough-related contributing factors were denied. The patient reported that his cough mainly occurred at nighttime and was aggravated in the supine position. Vomiting could occur when the cough was violent. He denied fever, dysphonia, chest tightness, wheezing, chest pain and hemoptysis, abdominal pain, and bloating. The patient had initially presented to the local hospital and underwent a chest CT scan. The chest CT scan showed slight and scattered patchy infiltration in bilateral lung fields and without other significant pulmonary lesions. Anti-infective treatment was administered but was not effective for ameliorating the cough symptoms. He then received an inhaled corticosteroid, antihistamines, antileukotriene agents, or proton pump inhibitors for 6 months. However, all these treatments failed to alleviate the patient's cough. He had a history of hypertension and hyperlipidemia for > 10 years and was treated with valsartan (an angiotensin II receptor blocker) and atorvastatin. In the past year, the patient had lost 10 kg of weight, and his current BMI was 27.72 kg/m2.

Updates to the modern diagnosis of GERD: Lyon consensus 2.0.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

Development and Validation of Serum Markers as Noninvasive Diagnostic Methods for Achalasia.

INTRODUCTION: Currently, the diagnosis of achalasia mainly relies on invasive or radioactive examinations. This study aimed to develop a noninvasive diagnostic method for achalasia based on specific serum markers. METHODS: Serum levels of profilin-1, galectin-10, immunoglobulin heavy variable 3-9, vasodilator-stimulated phosphoprotein, and transgelin-2 were measured in patients with achalasia and controls by enzyme-linked immunosorbent assay. The diagnostic values and thresholds were determined by the receiver operating characteristic curve analysis. Then, patients with dysphagia were prospectively enrolled to validate the ability of these molecules for achalasia diagnosing. RESULTS: A total of 142 patients with achalasia and 50 nonachalasia controls (healthy volunteers and patients with reflux esophagitis) were retrospectively included. The serum levels of profilin-1, galectin-10, and transgelin-2 in patients with achalasia were significantly higher than those in healthy volunteers and patients with reflux esophagitis ( P all < 0.001). Profilin-1, galectin-10, and transgelin-2 were of good performance in diagnosing achalasia, with optimal thresholds of 2,171.2, 33.9, and 1,630.6 pg/mL, respectively. Second, 40 patients with dysphagia were prospectively enrolled to the validation of achalasia. For profilin-1, the positive predictive value, negative predictive value, sensitivity, and specificity were 100.0%, 64.5%, 45.0%, and 100.0%, respectively. The figures for transgelin-2 were 65.5%, 90.9%, 95.0%, and 50.0%. When both increased, the positive predictive value reached to 100.0%. When both indexes were normal, the negative predictive value was 100.0%. DISCUSSION: Profilin-1 and transgelin-2 were promising biomarkers for achalasia diagnosis and performed better in combination. Further multicenter studies are necessary to verify their application as preliminary screening tools for achalasia.

Current complementary and alternative therapy forgastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a widely prevalent gastrointestinal disorder, affecting ∼13.3% of the global population. There are shortages and limitations of current GERD treatment modalities, and complementary and alternative therapy (CAT) is a promising option to fill in the gap. Dietary and lifestyle modifications might play an important and complementary role in alleviating GERD symptoms. Traditional Chinese medicine and brain-gut behavior therapy, particularly transcutaneous electrical acustimulation and diaphragmatic breathing therapy were shown to be useful adjuncts or alternatives in treating GERD. CAT may help to relieve GERD symptoms, minimize medication dosage, and slow the demand for surgery. The aim of this review was to summarize the existing evidence of some common CATs in treating symptomatic GERD, including dietary modification, lifestyle change, traditional Chinese medicine, and brain-gut behavior therapy.

Clinical relevance of salivary pepsin detection in diagnosing gastroesophageal reflux disease subtypes.

Background: Gastroesophageal reflux disease (GERD) is heterogeneous with a varied symptom spectrum and reflux profiles. Its definite diagnosis often requires invasive tools including endoscopy or reflux monitoring. The aim of this study was to investigate the clinical relevance of salivary pepsin detection as a non-invasive screening tool to diagnose GERD of different subtypes. Methods: A total of 77 patients with suspected GERD symptoms and 12 asymptomatic controls were analysed. All participants performed symptom evaluation, upper endoscopy, esophageal manometry, and 24-hour multichannel intraluminal impedance-dual pH probe monitoring. Saliva was self-collected across three different time points: at early fasting, postprandially, and at symptom occurrence. Salivary pepsin levels were measured via Peptest. The optimal threshold of salivary pepsin for diagnosing distal or proximal reflux was determined according to a receiver-operating characteristic curve. Results: The average salivary pepsin concentration of suspected GERD patients was significantly higher than that of controls (100.63 [68.46, 141.38] vs 67.90 [31.60, 115.06] ng/mL, P = 0.044), although no difference was found among patients with different symptom spectrums. The distal reflux group had a higher average pepsin concentration than non-reflux patients (170.54 [106.31, 262.76] vs 91.13 [63.35, 127.63] ng/mL, P = 0.043), while no difference was observed between the distal reflux group and the proximal reflux group. The optimal cut-off value of salivary pepsin concentration for diagnosing pathological distal reflux was 157.10 ng/mL, which was higher than that for diagnosing pathological proximal reflux (122.65 ng/mL). The salivary pepsin concentration was significantly correlated with distal and proximal reflux parameters. Conclusions: Salivary pepsin measurement can help in identifying true GERD with pathological distal reflux or proximal reflux, regardless of different symptom spectrums. A higher threshold should be applied for diagnosing distal reflux than for proximal reflux.

The molecular pathogenesis of achalasia: a paired lower esophageal sphincter muscle and serum 4D label-free proteomic study.

Background: Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia. Methods: Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia. Results: Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P < 0.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix-receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples. Conclusions: This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.

Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Achalasia: The Current Clinical Dilemma and Possible Pathogenesis.

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients' quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Clinical outcomes of asymptomatic low-grade esophagitis: results from a multicenter Chinese cohort.

Background: Asymptomatic low-grade (Los Angeles Classification Grades A and B) esophagitis is common in clinical practice with unclear clinical outcomes. This study aimed to explore the clinical outcomes of asymptomatic low-grade esophagitis. Methods: This was a multicenter cohort study conducted by three academic hospitals in China. Asymptomatic low-grade esophagitis patients between January 2015 and December 2019 were included. Mucosal healing condition 1 year after initial diagnosis, symptom outcomes, and proton-pump inhibitor (PPI) use within 1 year after initial diagnosis were studied and compared. Results: A total of 248 asymptomatic low-grade esophagitis patients were included. Esophagitis disappeared in 76.2% of patients 1 year after initial diagnosis. In terms of symptom outcomes, 89.9% of patients did not present gastroesophageal reflux disease (GERD) symptoms within 1 year after initial diagnosis. No significant difference was found in the proportion of patients who presented GERD symptoms and in the proportion of patients with persistent esophagitis between the PPI group and the non-PPI group (all P > 0.05). Patients with initial Grade B esophagitis were more likely to present follow-up GERD symptoms (16.0% vs 7.5%, P = 0.041) and had more severe follow-up esophagitis than those with Grade A (P < 0.001). Patients with follow-up GERD symptoms were more likely to have persistent esophagitis than those without. Conclusions: This study demonstrated that asymptomatic low-grade esophagitis had relatively benign clinical outcomes. Patients with initial Grade B esophagitis and patients with follow-up GERD symptoms were more likely to be those who are in genuine need of further follow-up and treatments.

The role of vonoprazan in patients with erosive esophagitis.

Acid suppression is the primary therapy for erosive esophagitis (EE). Although proton pump inhibitors (PPIs) are considered as the first-line medication for EE, 10-20% of patients with Los Angeles C and D grade EE do not gain complete mucosal healing and symptom control despite 8-week double-dose PPI treatment. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which blocks the H+, K+-adenosine triphosphatase enzymes in a K+-competitive and reversible manner. Vonoprazan exhibits different pharmacological and pharmacokinetic profiles from conventional PPIs, and has a rapid, potent and sustained acid inhibitory effect. In this review, we summarized and discussed current evidence regarding the role of vonoprazan in terms of mucosal healing, maintaining remission and symptom relief for the management of EE, including the initial and maintenance treatment of EE, as well as for PPI-resistant EE patients. Safety concerns and cost-effectiveness analysis of vonoprazan were also mentioned in the article. As a potent and well-tolerated acid blocker, vonoprazan has the potential to become a novel option for the management of EE.

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.).

Zhizhu Kuanzhong Capsule in treating patients with functional dyspepsia postprandial distress syndrome: study protocol for a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial.

BACKGROUND: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders. Based on the various symptoms present in patients with functional dyspepsia postprandial distress syndrome (FD-PDS), routine agents such as acid suppressants, prokinetic drugs, and centrally acting drugs, offer limited treatment choices with potential side effects. As a preliminary clinical trial showed that the marketed product Zhizhu Kuanzhong Capsule (ZZKZ) can improve symptoms in FD-PDS patients, our study aims to provide further evidence on the clinical efficacy and safety of ZZKZ in the treatment of patients with FD-PDS. METHODS: In this multicenter, randomized, patient- and investigator-blinded, placebo-controlled, parallel-group clinical trial, we will recruit patients with FD-PDS from 18 hospitals in China and Australia. The trial will enroll patients with FD-PDS based on the Rome IV diagnostic criteria. A total of 480 eligible patients will be randomized 1:1 into either ZZKZ or placebo group with 8 weeks of treatment and 4 weeks of follow-up. The primary endpoint will be measured by a self-rated Visual Analogue Score (VAS) for the degree of discomfort with both symptoms of postprandial fullness and early satiation, recorded once a day and 7 days a week. The primary analysis will aim to compare the response rate for FD-PDS VAS score between the groups before and after 8 weeks of treatment with an alpha level of 0.05 (2-sided). DISCUSSION: This trial aims to strengthen the evidence for the efficacy and safety of ZZKZ, a marketed product, in treating FD-PDS. Compared to the previous clinical trial that targeted FD-PDS, this trial will have an 8-week double-blind treatment period to investigate the effect of long-term mediation through comparison with the placebo group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03825692 . Registered on 28 January 2019.

The efficacy and safety of keverprazan, a novel potassium-competitive acid blocker, in treating erosive oesophagitis: a phase III, randomised, double-blind multicentre study.

BACKGROUND: Keverprazan is a novel potassium-competitive acid blocker (P-CAB) with a strong acid-suppressive capacity that may provide clinical benefit in acid-related diseases. AIMS: This study aimed to explore the non-inferior efficacy and safety of keverprazan to lansoprazole in treating erosive oesophagitis (EO). METHODS: This was a phase III, randomised, double-blind multicentre study. Patients were randomised to receive keverprazan 20 mg once daily or lansoprazole 30 mg once daily for 4-8 weeks. EO healing rates and adverse events (AEs) were compared between the keverprazan group and the lansoprazole group. RESULTS: A total of 238 patients comprised the full analysis set (FAS) while 221 patients comprised the per-protocol set (PPS). For FAS analysis, the EO healing rates at week 8 were 95.8% (114/119) and 89.9% (107/119) for keverprazan and lansoprazole respectively. For PPS analysis, the EO healing rates at week 8 were 99.1% (110/111) and 92.7% (102/110) for keverprazan and lansoprazole respectively. Non-inferiority of keverprazan compared with lansoprazole according to EO healing rates at 8 weeks was demonstrated in both FAS (difference: 5.8% [95% CI: -0.6% to 12.3%]; p = 0.081) and PPS (difference: 6.1% [95% CI: 1.1%-11.2%]; p = 0.018) analysis. Drug-related AEs were reported in 34.5% (41/119) patients of the keverprazan group and 25.2% (30/119) patients of the lansoprazole group with no significant difference (p = 0.156). No severe AE happened in the keverprazan group. CONCLUSIONS: This study demonstrated the non-inferior efficacy of keverprazan to lansoprazole in treating EO. The incidences of drug-related AEs were comparable between keverprazan and lansoprazole.

Successful management of exudate and odor using a pouch system in a patient with malignant facial wound: A case report.

Malignant fungating wounds are associated with heavy exudate and malodor, and can thus have a devastating impact on the physical, psychological, and functional health of patients at the end of life. Management is typically limited to the use of more absorbent dressings and frequent changing of dressings. However, this method is associated with a large amount of time needed for wound care, and does not always resolve the problem of malodor. Herein, we report the use of an inexpensive ostomy pouch to manage facial fungating wounds caused by maxillary gingival carcinoma. The pouches are adhered to the skin, and collect a large amount of malodorous exudate for days without leaking. Fewer dressing changes and the absence of malodor result in an improved quality of life for the patient and family.