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BMC Gastroenterology May 2023VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.
BACKGROUND
VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole.
METHODS
Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology.
RESULTS
Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified.
CONCLUSIONS
In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).
Topics: Humans; Proton Pump Inhibitors; Hyperplasia; Esophagitis; Lansoprazole; Peptic Ulcer; Treatment Outcome; 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Double-Blind Method
PubMed: 37127558
DOI: 10.1186/s12876-023-02772-w -
Molecular Medicine (Cambridge, Mass.) Feb 2022Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine...
BACKGROUND
Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts.
METHODS
A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin-Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting.
RESULTS
After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability.
CONCLUSIONS
Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca]) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.
Topics: Animals; Calcium; Calcium Signaling; Lansoprazole; Mice; Mice, Inbred ICR; Osteoblasts; Osteoporosis
PubMed: 35183103
DOI: 10.1186/s10020-022-00448-x -
Clinical and Translational... Jul 2023Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the... (Randomized Controlled Trial)
Randomized Controlled 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.
Topics: Humans; Lansoprazole; Duodenal Ulcer; Anti-Ulcer Agents; Double-Blind Method
PubMed: 37235793
DOI: 10.14309/ctg.0000000000000602 -
Gut Sep 2016The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter... (Randomized Controlled Trial)
Randomized Controlled Trial
Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study.
OBJECTIVE
The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy.
DESIGN
A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment.
RESULTS
Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated.
CONCLUSION
Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer.
TRIAL REGISTRATION NUMBER
NCT01505127.
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Breath Tests; Clarithromycin; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Peptic Ulcer; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome
PubMed: 26935876
DOI: 10.1136/gutjnl-2015-311304 -
International Journal of Environmental... Nov 2022Proton pump inhibitor (PPI) lansoprazole acts as a liver X receptor agonist, which plays a crucial role in the crosstalk of osteoblasts and osteoclasts in vitro and...
BACKGROUND
Proton pump inhibitor (PPI) lansoprazole acts as a liver X receptor agonist, which plays a crucial role in the crosstalk of osteoblasts and osteoclasts in vitro and during bone turnover in vivo. However, epidemiological studies on the association between the use of lansoprazole and osteoporosis risk are limited. We aimed to determine the risk of developing osteoporosis in patients with lansoprazole use.
METHODS
A retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study includes 655 patients with lansoprazole use (the exposed cohort) and 2620 patients with other PPI use (the comparison cohort). The main outcome was the primary diagnosis of osteoporosis. The hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the association between the use of lansoprazole and risk of osteoporosis.
RESULTS
Patients receiving lansoprazole treatment had a reduced risk of osteoporosis as compared with those undergoing other PPI therapy (adjusted HR, 0.56; 95% CI, 0.46-0.68). Moreover, this inverse association is evident in both sexes and in various age groups.
CONCLUSIONS
This population-based cohort study demonstrated that lansoprazole use was associated with a reduced risk of osteoporosis. The clinical implications of the present study need further investigations.
Topics: Male; Female; Humans; Cohort Studies; Lansoprazole; Retrospective Studies; Osteoporosis; Proton Pump Inhibitors
PubMed: 36430077
DOI: 10.3390/ijerph192215359 -
Journal of Food and Drug Analysis Mar 2022Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is...
Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing of compounds against Leishmania amastigotes and selected the most promising active compounds, Lansoprazole and Posaconazole. We identified possible Leishmania drug targets of Lansoprazole and Posaconazole using several available servers. Our in-silico screen identified likely Lansoprazole targets as the closely related calcium-transporting ATPases (LdBPK_352080.1, LdBPK_040010.1, and LdBPK_170660.1), and the Posaconazole target as lanosterol 14-alpha-demethylase (LdBPK_111100.1). Further validation showed LdBPK_352080.1 to be the most plausible target based on induced-fit docking followed by long (100ns) MD simulations to confirm the stability of the docked complexes. We present a likely ion channel-based mechanism of action of Lansoprazole against Leishmania calcium-transporting ATPases, which are essential for parasite metabolism and infectivity. The LdBPK_111100.1 interaction with Posaconazole is very similar to the known fungal orthologue. Herein, we present two novel anti-leishmanial agents, Posaconazole and Lansoprazole, already approved by the FDA for different indications and propose plausible mechanisms of action for their antileishmanial activity.
Topics: Antiprotozoal Agents; Drug Repositioning; Humans; In Vitro Techniques; Lansoprazole; Leishmania; Leishmaniasis; Triazoles
PubMed: 35647721
DOI: 10.38212/2224-6614.3394 -
BMJ Case Reports Jan 2014The introduction of proton pump inhibitors (PPIs) in the late 1980s optimised the medical treatment of acid-related disorders. They are potent medications and have a...
The introduction of proton pump inhibitors (PPIs) in the late 1980s optimised the medical treatment of acid-related disorders. They are potent medications and have a good safety profile. However, long-term therapy with PPIs may carry undesired side effects, one of which is hypomagnesaemia. This entity is likely to be under-reported. We present a clinical case which illustrates this important clinical problem. We present the case of a 73-year-old woman who was admitted to the hospital with supraventricular tachycardia due to hypomagnesaemia while using lansoprazole, followed by the literature review on this subject. In our patient after the intravenous magnesium replenishment, her arrhythmia resolved. After stopping her PPI her serum magnesium remained within reference values without oral supplementation. We believe that more attention towards this underdiagnosed side effect is required. Serum magnesium concentration should be checked in patients on PPIs if they are unwell or present with arrythmia.
Topics: Aged; Female; Humans; Hypocalcemia; Lansoprazole; Magnesium; Magnesium Deficiency; Proton Pump Inhibitors; Tachycardia, Supraventricular; Withholding Treatment
PubMed: 24414180
DOI: 10.1136/bcr-2012-006342 -
Alimentary Pharmacology & Therapeutics Jan 2023Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders.
AIM
To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels.
RESULTS
We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients.
CONCLUSIONS
Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.
Topics: Humans; Lansoprazole; Gastrins
PubMed: 36314172
DOI: 10.1111/apt.17255 -
Journal of Biosciences 2020Alternate remedies with natural products provides unlimited opportunities for new drug development. These can be either as pure compounds or as standardized set of... (Review)
Review
Alternate remedies with natural products provides unlimited opportunities for new drug development. These can be either as pure compounds or as standardized set of compounds. The phytochemicals and secondary metabolites are in great demand for screening bioactive compounds and plays an important role towards drug development. Natural products have many advantages over to synthetic chemical drugs. (H. pylori) a Gram-negative bacteria has been classified as Class I carcinogen by World Health Organization in 1994. Current treatment regimens for is 'triple therapy' administrated for two weeks which includes a combination of two antibiotics like Amoxicillin and Clarithromycin and a proton pump inhibitor (PPI) like Lansoprazole, and for 'quadruple therapy' in addition to antibiotics and a PPI, Bismuth is used. Antibiotic resistance can be named as the main factor for failure of treatment of infection. The need of the hour is to develop a herbal remedy that could combat the growth of . Probiotics can also be used as 'feasible' tool for infection management. Present review is an attempt to briefly discuss about the pathogenicity, genetic predisposition, perturbation of gut microbiota due to antibiotic treatment and restoration of healthy gut microbiota with phytochemicals and probiotics.
Topics: Amoxicillin; Anti-Bacterial Agents; Biological Products; Bismuth; Clarithromycin; Drug Therapy, Combination; Dysbiosis; Gastrointestinal Microbiome; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Phytochemicals; Plant Extracts; Plants, Medicinal; Probiotics
PubMed: 32975237
DOI: 10.1007/s12038-020-00078-7 -
Einstein (Sao Paulo, Brazil) 2022To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type...
Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study.
OBJECTIVE
To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type 1 diabetes.
METHODS
Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed.
RESULTS
Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported.
CONCLUSION
Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual β-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies.
REGISTRY OF CLINICAL TRIALS
(www.ctri.nic.in) under number REF/2021/03/041415 N.
Topics: Child; Humans; Insulin; Diabetes Mellitus, Type 1; Pilot Projects; Cholecalciferol; Lansoprazole; C-Peptide; Blood Glucose; Disease Progression
PubMed: 36449759
DOI: 10.31744/einstein_journal/2022AO0149