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Gastroenterology Jan 2023For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more potent acid inhibition than PPIs, but data on its efficacy for erosive esophagitis are limited.
METHODS
Adults with erosive esophagitis were randomized to once-daily vonoprazan, 20 mg, or lansoprazole, 30 mg, for up to 8 weeks. Patients with healing were rerandomized to once-daily vonoprazan, 10 mg, vonoprazan, 20 mg, or lansoprazole, 15 mg, for 24 weeks. Primary end points, percentage with healing by week 8 endoscopy, and maintenance of healing at week 24 endoscopy, were assessed in noninferiority comparisons (noninferiority margins, 10%), with superiority analyses prespecified if noninferiority was demonstrated. Analyses of primary and secondary end points were performed using fixed-sequence testing procedures.
RESULTS
Among 1024 patients in the healing phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the exploratory analysis of healing (92.9 vs 84.6%; difference, 8.3%; 95% confidence interval [CI], 4.5%-12.2%). Secondary analyses showed vonoprazan was noninferior in heartburn-free days (difference, 2.7%; 95% CI, -1.6% to 7.0%), and superior in healing Los Angeles Classification Grade C/D esophagitis at week 2 (difference, 17.6%; 95% CI, 7.4%-27.4%). Among 878 patients in the maintenance phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the secondary analysis of maintenance of healing (20 mg vs lansoprazole: difference, 8.7%; 95% CI, 1.8%-15.5%; 10 mg vs lansoprazole: difference, 7.2%; 95% CI, 0.2%-14.1%) and secondary analysis of maintenance of healing Grade C/D esophagitis (20 mg vs lansoprazole: difference, 15.7%; 95% CI, 2.5%-28.4%; 10 mg vs lansoprazole: difference, 13.3%; 95% CI, 0.02%-26.1%).
CONCLUSIONS
Vonoprazan was noninferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis. (ClinicalTrials.gov: NCT04124926).
Topics: Adult; Humans; Lansoprazole; Pyrroles; Sulfonamides; Esophagitis; Proton Pump Inhibitors; Peptic Ulcer; Treatment Outcome
PubMed: 36228734
DOI: 10.1053/j.gastro.2022.09.041 -
Alimentary Pharmacology & Therapeutics Sep 2020Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders.
AIMS
To assess whether tegoprazan is non-inferior to lansoprazole in terms of efficacy and safety in patients with gastric ulcers.
METHODS
In this phase 3, double-blind, active control, multicentre study, 306 gastric ulcer patients were randomised to one of three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg once daily for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed ulcers confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms and safety were assessed.
RESULTS
In the full analysis set, the cumulative healing rates at week 8 were 94.8% (91/96) for the tegoprazan 50 mg, 95.0% (94/99) for the tegoprazan 100 mg and 95.7% (89/93) for the lansoprazole 30 mg groups. At week 4, the respective healing rates were 90.6% (87/96), 91.9% (91/99), and 89.2% (83/93). In per protocol analysis, 4-week healing rates were 95.4% (84/88), 94.6% (88/93) and 92.9% (79/85) for tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg, respectively. Both doses of tegoprazan were non-inferior to lansoprazole in ulcer healing at 4 and 8 weeks. The incidence of drug-related treatment-emergent adverse events did not differ among groups. The increase in serum gastrin concentration was not higher in tegoprazan-treated patients than in lansoprazole-treated patients.
CONCLUSIONS
Tegoprazan 50 or 100 mg were not inferior to lansoprazole 30 mg once daily in the treatment of gastric ulcers.
Topics: Adult; Aged; Anti-Ulcer Agents; Benzene Derivatives; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Imidazoles; Lansoprazole; Male; Middle Aged; Potassium; Proton Pump Inhibitors; Republic of Korea; Stomach Ulcer; Treatment Outcome; Wound Healing
PubMed: 32701188
DOI: 10.1111/apt.15865 -
JAMA Network Open Oct 2023The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates...
IMPORTANCE
The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes.
OBJECTIVE
To compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021.
EXPOSURE
Lansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications.
RESULTS
Of the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.
Topics: Adult; Humans; Male; Aged; Female; Lansoprazole; Ceftriaxone; Cohort Studies; Retrospective Studies; Arrhythmias, Cardiac; Heart Arrest; Proton Pump Inhibitors; Inpatients; Ontario
PubMed: 37883084
DOI: 10.1001/jamanetworkopen.2023.39893 -
Gut Feb 2020To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). (Comparative Study)
Comparative Study Randomized Controlled Trial
Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.
OBJECTIVE
To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).
DESIGN
In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).
RESULTS
In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.
CONCLUSION
Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.
TRIAL REGISTRATION NUMBER
NCT02388724.
Topics: Adult; Aged; Double-Blind Method; Drug Administration Schedule; Esophagitis, Peptic; Female; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Severity of Illness Index; Sulfonamides; Treatment Outcome; Wound Healing
PubMed: 31409606
DOI: 10.1136/gutjnl-2019-318365 -
Alimentary Pharmacology & Therapeutics Jan 2016Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders.
AIM
To verify the non-inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long-term safety and efficacy as maintenance therapy.
METHODS
In this multicentre, randomised, double-blind, parallel-group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A-D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re-randomised into a long-term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks.
RESULTS
Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long-term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non-inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long-term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well-tolerated.
CONCLUSIONS
The non-inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well-tolerated and effective during the long-term maintenance study.
Topics: Adult; Aged; Cytochrome P-450 CYP2C19; Double-Blind Method; Esophagitis; Female; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Recurrence; Sulfonamides; Wound Healing
PubMed: 26559637
DOI: 10.1111/apt.13461 -
Indian Journal of Gastroenterology :... Aug 2023Proton-pump inhibitors (PPIs) are the mainstay of treatment in erosive esophagitis (EE). An alternative to PPIs in EE is Vonoprazan, a potassium competitive acid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Proton-pump inhibitors (PPIs) are the mainstay of treatment in erosive esophagitis (EE). An alternative to PPIs in EE is Vonoprazan, a potassium competitive acid blocker. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing vonoprazan to lansoprazole.
METHODS
Multiple databases searched through November 2022. Meta-analysis was performed to assess endoscopic healing at two, four and eight weeks, including for patients with severe EE (Los Angeles C/D). Serious adverse events (SAE) leading to drug discontinuation were assessed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
RESULTS
Four RCTs with 2208 patients were included in the final analysis. Vonoprazan 20 mg once-daily was compared to lansoprazole 30 mg once-daily dosing. Among all patients, at two and eight weeks post-treatment, vonoprazan resulted in significantly higher rates of endoscopic healing as compared to lansoprazole, risk ratios (RR) 1.1, p<0.001 and RR 1.04, p=0.03. The same effect was not observed at four weeks, RR 1.03 (CI 0.99-1.06, I=0%) following therapy. Among patients with severe EE, vonoprazan resulted in higher rates of endoscopic healing at two weeks, RR 1.3 (1.2-1.4, I=47%), p=<0.001, at four weeks, RR 1.2 (1.1-1.3, I=36%), p=<0.001 and at eight weeks post-treatment, RR 1.1 (CI 1.03-1.3, I=79%), p=0.009. We found no significant difference in the overall pooled rate of SAE and pooled rate of adverse events leading to drug discontinuation. Finally, the overall certainty of evidence for our main summary estimates was rated as high (grade A).
CONCLUSION
Based on limited number of published non-inferiority RCTs, our analysis demonstrates that among patients with EE, vonoprazan 20 mg once-daily dosing achieves comparable and in those with severe EE, higher endoscopic healing rates as compared to lansoprazole 30 mg once-daily dosing. Both drugs have a comparable safety profile.
Topics: Humans; Lansoprazole; Randomized Controlled Trials as Topic; Esophagitis; Proton Pump Inhibitors; Pyrroles; Peptic Ulcer
PubMed: 37418052
DOI: 10.1007/s12664-023-01384-2 -
The Turkish Journal of Gastroenterology... Sep 2016Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease.
BACKGROUND/AIMS
Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype.
MATERIALS AND METHODS
Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients.
RESULTS
On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment.
CONCLUSION
Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Cross-Over Studies; Cytochrome P-450 CYP2C19; Double-Blind Method; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Genotype; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome
PubMed: 27782887
DOI: 10.5152/tjg.2016.15514 -
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 -
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 -
Progress in Neuro-psychopharmacology &... Jan 2023As a heterogeneous disorder, schizophrenia is known to be associated with neuroinflammation. A recent study showed that several cytokines are higher in the plasma and...
As a heterogeneous disorder, schizophrenia is known to be associated with neuroinflammation. A recent study showed that several cytokines are higher in the plasma and cerebrospinal fluid of schizophrenia patients. Lansoprazole, a proton pump inhibitor used for treating erosive esophagitis, has been reported to reduce INF-γ-induced neurotoxicity and decrease inflammatory cytokines including IL-1β, IL-6, and TNF-α. These findings persuaded us to examine whether lansoprazole ameliorates schizophrenia-like symptoms. The schizophrenia mouse model was induced by the acute administration of MK-801, an NMDA receptor antagonist. Sensorimotor gating, Barnes maze, and social novelty preference tests were conducted to evaluate schizophrenia-like behaviors. We found that lansoprazole (0.3, 1, or 3 mg/kg) ameliorated sensorimotor gating deficits, spatial learning, and social deficits caused by MK-801 treatment (0.2 mg/kg). The catalepsy test, balance beam test, and rotarod test were performed to reveal the adverse effects of lansoprazole on motor coordination. The behavioral results indicated that lansoprazole did not result in any motor function deficits. Moreover, lansoprazole decreased inflammatory cytokines including IL-6 and TNF-α only in the cortex, but not in the hippocampus. Collectively, these results suggest that lansoprazole could be a potential candidate for treating schizophrenia patients who suffer from sensorimotor gating deficits or social disability without any motor-related adverse effects.
Topics: Animals; Mice; Dizocilpine Maleate; Interleukin-6; Lansoprazole; Proton Pump Inhibitors; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Tumor Necrosis Factor-alpha; Disease Models, Animal
PubMed: 36191804
DOI: 10.1016/j.pnpbp.2022.110646