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Intensive Care Medicine Apr 2022Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump... (Randomized Controlled Trial)
Randomized Controlled Trial
The effects of pantoprazole vs. placebo on 1-year outcomes, resource use and employment status in ICU patients at risk for gastrointestinal bleeding: a secondary analysis of the SUP-ICU trial.
PURPOSE
Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump inhibitors, is widely used in the attempt to prevent this. In this secondary analysis of Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, we assessed 1-year outcomes in the pantoprazole vs. placebo groups.
METHODS
In the SUP-ICU trial, 3298 acutely admitted ICU patients at risk of GI bleeding were randomly allocated, stratified for site, to pantoprazole or placebo. In this secondary analysis, we assessed clinically important GI bleedings in ICU and 1-year mortality, health care resource use (e.g. readmission with GI bleeding, use of home care and general practitioner), health care costs, and employment status for the Danish participants using registry data.
RESULTS
Among the 2099 Danish participants, 2092 had data in the registries; 1045 allocated to pantoprazole and 1047 to placebo. The number of clinically important GI bleedings in ICU was 1.9 percentage points [95% CI 0.3-3.5] lower in the pantoprazole group vs. the placebo group, but none of the 1-year outcomes differed statistically significantly between groups, including total health care costs (€1954 [- 2992 to 6899]), readmission with GI bleeding (- 0.005 admissions [- 0.016 to 0.005]), 1-year mortality (- 0.013 percentage points [- 0.051 to 0.026]), and employment (- 0.178 weeks [- 0.390 to 0.034]).
CONCLUSION
Among ICU patients at risk of GI bleeding, pantoprazole reduced clinically important GI bleeding in ICU, but this did not translate into a reduction in 1-year mortality, health care resource use or improvements in employment status.
Topics: Employment; Gastrointestinal Hemorrhage; Humans; Intensive Care Units; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 35122105
DOI: 10.1007/s00134-022-06631-2 -
Trials Jun 2020Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: •...
Impact of pantoprazole on absorption and disposition of hydroxychloroquine, a drug used in Corona Virus Disease-19 (Covid-19): A structured summary of a study protocol for a randomised controlled trial.
OBJECTIVES
Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: • Evaluation of the relationship between HCQ concentrations in whole blood, plasma and intracellular concentrations in target cells - peripheral blood mononuclear cells (PBMCs). • Evaluation of HCQ as a potential perpetrator in drug-drug interactions at the level of cytochrome P450 (CYP) 3A4 and CYP2D6 (major drug metabolizing enzymes).
TRIAL DESIGN
Single centre, open-label, parallel group, two-arm, phase I drug-drug interaction trial.
PARTICIPANTS
Healthy volunteers (18-60 years old) are treated in the Clinical Pharmacological Trial Center of Heidelberg University Hospital, Germany.
INTERVENTION AND COMPARATOR
• Participants are randomized in a group to either receive a nine-day course of pantoprazole, or to a control group without pantoprazole. All participants receive a single dose of HCQ 400 mg. • Additionally, CYP3A4 and CYP2D6 phenotyping with microdosed probe drugs is performed using midazolam and yohimbine as enzyme activity markers, respectively.
MAIN OUTCOMES
Primary endpoint: Area under the curve (AUC) and maximum concentration (C) of a single oral dose of 400 mg HCQ with and without pantoprazole (changes in these two values describe relevant aspects of exposure to HCQ with and without administration of pantoprazole). Secondary endpoints: • AUC, AUC and C of midazolam and yohimbine. • Correlation of HCQ concentrations in whole blood with concentrations in plasma and peripheral blood mononuclear cells (PBMC).
RANDOMISATION
Participants are assigned to treatment groups by using a randomisation list (1:1, block size = 4) and consecutive enrolment.
BLINDING (MASKING)
The trial is an open-label trial, participants and investigators are not blinded.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE)
A total number of 24 participants (12 per group) are planned to be randomised.
TRIAL STATUS
Protocol version 2.1 dated 24/04/2020, first patient first visit. April 30th, 2020, recruitment ongoing, anticipated end of study June 30th, 2020.
TRIAL REGISTRATION
EudraCT Number: 2020-001470-30 , registered on 31 March 2020 German Clinical trials register number / International Clinical Trials Registry Platform: DRKS00021573, registered on 27 April 2020 FULL PROTOCOL: The full trial protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full trial protocol. The trial protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
Topics: Adolescent; Adult; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Interactions; Humans; Hydroxychloroquine; Middle Aged; Pandemics; Pantoprazole; Pneumonia, Viral; Randomized Controlled Trials as Topic; SARS-CoV-2; Young Adult; COVID-19 Drug Treatment
PubMed: 32600363
DOI: 10.1186/s13063-020-04476-y -
Journal of Analytical Toxicology Nov 2017Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause...
Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause a false-positive cannabinoid urine screen. However, a case of false-positive urine cannabinoid screen in a patient who received a pantoprazole dose has been recently published. The purpose of this study was to determine the potential cross-reactivity of pantoprazole in the cannabinoid immunoassays: Alere Triage® TOX Drug Screen, KIMS® Cannabinoids II and DRI® Cannabinoids Assay. Drug-free urine to which pantoprazole was added up to 12,000 μg/mL produced negative results in the DRI® Cannabinoids and KIMS® Cannabinoids II. Alere Triage® TOX Drug Screen assay gave positive results at pantoprazole concentrations higher than 1,000 μg/mL. Urine samples from 8 pediatric patients were collected at the beginning of their pantoprazole treatment. Alere Triage® TOX Drug Screen assay produced positive test results in all patient samples and KIMS® Cannabinoids II immunoassay produced positive test results in one patient sample. None patient sample gave a false-positive result when analyzed by the DRI® Cannabinoids Assay. Our findings demonstrate that some cannabinoids immunoassays are susceptible to cross-reaction errors resulting from the presence in urine of pantoprazole and the resulting metabolism of the parent drug. Clinicians should be aware of the possibility of false-positive results for cannabinoids after a pantoprazole treatment.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Cannabinoids; False Positive Reactions; Humans; Immunoassay; Pantoprazole; Proton Pump Inhibitors; Substance Abuse Detection; Urinalysis
PubMed: 28985315
DOI: 10.1093/jat/bkx047 -
Therapeutic Apheresis and Dialysis :... Oct 2020Renal allograft survival requires multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro-protective medications,... (Comparative Study)
Comparative Study Randomized Controlled Trial
Renal allograft survival requires multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro-protective medications, notably, proton pump inhibitors (PPI). This study aimed to compare the influence of pantoprazole and esomeprazole on serum cyclosporine trough levels (C ) in renal transplant recipients (RTR). A prospective, parallel, open-label trial was conducted on 47 adult RTR receiving cyclosporine doses adjusted to attain trough concentrations of 100 to 150 μg/L, mycophenolate mofetil (MMF) 750 mg q12 hour and prednisolone at 5 mg daily at Nasser Institute, Cairo, Egypt from January to September 2016. Patients were randomized into the esomeprazole group (25) or pantoprazole group (22) receiving the same dose (40 mg once daily). The study outcomes included clinical signs of rejection and renal function decline, assessed by elevations in serum creatinine, caused by cyclosporine level variations in either of the two study groups. Renal function, C and CBC measurements were measured at baseline and monthly for 6 months. The mean C values were higher in the pantoprazole group than in the esomeprazole group in the sixth month only (P = .007). Serum creatinine level was lower in the sixth month than at baseline in the esomeprazole group (P = .004). There were no signs of rejection biochemical or clinical in any of the study groups. In conclusion, PPIs should be used with caution and doses should be titrated to reach the C targets in RTR, which is of more importance in pantoprazole than esomeprazole to avoid C level elevation or decline affecting the allograft function.
Topics: Adult; Aged; Cyclosporine; Esomeprazole; Female; Humans; Kidney Transplantation; Male; Middle Aged; Pantoprazole; Prospective Studies; Proton Pump Inhibitors; Young Adult
PubMed: 31856374
DOI: 10.1111/1744-9987.13464 -
Mediators of Inflammation 2015Proton pump inhibitors (PPIs) are commonly prescribed drugs that decrease stomach acidity and are thus often used to treat gastroesophageal reflux disease and as a...
Proton pump inhibitors (PPIs) are commonly prescribed drugs that decrease stomach acidity and are thus often used to treat gastroesophageal reflux disease and as a preventative agent for the adverse effects of nonsteroidal anti-inflammatory drugs on the stomach mucosa. In recently published literature, an association between proton pump inhibitor administration and increased fracture risk has been stated. In order to reveal the underlying pathomechanisms of these observations, the effects of pantoprazole, a representative of the proton pump inhibitors, on human osteoclasts in vitro were evaluated in this study. Osteoclasts were stimulated with increasing concentrations of pantoprazole ranging from 0 μg/mL to 10 μg/mL over a period of seven days. Cell viability and tartrate-resistant acid phosphatase (TRAP) activity assays were performed after 1 day, 3 days, and 7 days, respectively. Here, stimulated osteoclasts presented a significantly lower viability and TRAP activity than the negative controls. Osteoclast-specific gene expression was evaluated after seven days and revealed no significant differences between all samples. Overall, the bone degrading and resorptive function of osteoclasts is inhibited by the administration of proton pump inhibitors. While PPI-related fractures through "basic multicellular unit" dysfunction are unlikely, the underlying pathomechanism remains unknown.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acid Phosphatase; Aged; Cell Survival; Cells, Cultured; Female; Humans; Isoenzymes; Male; Middle Aged; NF-kappa B; Osteoclasts; Pantoprazole; Proton Pump Inhibitors; Tartrate-Resistant Acid Phosphatase
PubMed: 25873758
DOI: 10.1155/2015/413097 -
Molecules (Basel, Switzerland) Feb 2022Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain...
Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of and genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the gene and upregulated the gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines' levels, and suppression of the MAPK (ERK1/2, JNK, p38)-NF-κB intracellular signaling pathway.
Topics: Animals; Apoptosis; Biomarkers; Biopsy; Cytokines; Disease Management; Disease Models, Animal; Disease Susceptibility; Immunohistochemistry; Inflammation Mediators; Kidney Diseases; MAP Kinase Signaling System; Male; Pantoprazole; Rats; Reperfusion Injury; Vincamine
PubMed: 35209172
DOI: 10.3390/molecules27041383 -
Scandinavian Journal of Gastroenterology Feb 1995Pantoprazole is a newly developed gastric H+/K(+)-adenosine triphosphatase inhibitor with a potent and long-acting inhibitory effect on gastric acid secretion. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Pantoprazole is a newly developed gastric H+/K(+)-adenosine triphosphatase inhibitor with a potent and long-acting inhibitory effect on gastric acid secretion.
METHODS
In a double-blind multicenter study with 28 centers in Germany, pantoprazole (40 mg before breakfast) was compared with ranitidine (300 mg at bedtime) with regard to healing rates, time until healing, symptom relief, and tolerability. A total of 248 outpatients with benign gastric ulcer were included.
RESULTS
The healing rates after 2, 4, and 8 weeks were 37%, 87%, and 97%, respectively, in the pantoprazole and 19%, 58%, and 80% in the ranitidine group. The differences between the two groups were significant at 2 weeks (p < 0.01), 4 weeks (p < 0.001), and 8 weeks (p < 0.001; Cochran/Mantel-Haenszel method). Ulcer healing proceeded significantly faster with pantoprazole (p < 0.001; Uleman's U-test). Both treatments were well tolerated.
CONCLUSIONS
Pantoprazole appears to be superior to ranitidine in gastric ulcer healing.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acute Disease; Benzimidazoles; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Ranitidine; Stomach Ulcer; Sulfoxides; Time Factors
PubMed: 7732331
DOI: 10.3109/00365529509093247 -
Alimentary Pharmacology & Therapeutics Jan 2014
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Pantoprazole; Proton Pump Inhibitors
PubMed: 24330238
DOI: 10.1111/apt.12565 -
Alimentary Pharmacology & Therapeutics Aug 1995Inhibition of the gastric proton pump is gaining acceptance as the treatment of choice for severe gastrooesophageal reflux disease, and for treatment of duodenal and... (Review)
Review
Inhibition of the gastric proton pump is gaining acceptance as the treatment of choice for severe gastrooesophageal reflux disease, and for treatment of duodenal and gastric ulceration. Three of these drugs are now available (omeprazole, lansoprazole and pantoprazole) and more are being developed. Proton pump inhibitors share the same core structure, but differ in terms of substituents on this core. The substitutions are able to modify some important chemical properties of the compounds. For example, pantoprazole is significantly more acid-stable than omeprazole or lansoprazole. E3810 is significantly less stable than the other compounds. We present an explantation for this finding that depends on the relative pK values for the pyridine and benzimidazole nitrogens, especially the former. Pantoprazole formulated in an enteric-coated tablet displays high bioavailability and linear pharmacokinetics whether on single or multiple dose regimens. Although all three proton pump inhibitors provide a similar chemical conversion to sulphenamides, which are highly reactive cysteine reagents, these reagents derivatize different cysteines in the extracytoplasmic or membrane domain of the pump and inhibit the pump at different rates. Whereas the differences in chemical reactivity can be explained by the solution chemistry of the compounds, selective derivatization of different cysteines on the protein argues for an involvement of pump structure in response to the presence of the proton pump inhibitor on its luminal surface. This suggests that the proton pump inhibitors, which were originally designed to take advantage of only the highly acidic space generated in the parietal cell by the production of the sulphenamide, are made even more selective by the protein they target. Pantoprazole is metabolized by a combination of phase I and phase II metabolism, and has also been shown to have a very low potential for drug interaction. Studies of acid secretion in man have shown this compound to be an effective and long lasting inhibitor of acid secretion. The pharmacodynamics explain the cumulative effect of repeated doses and maximal acid secretory capacity with a once daily dosage.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Duodenal Ulcer; Enzyme Inhibitors; Humans; Models, Molecular; Omeprazole; Pantoprazole; Peptic Ulcer; Proton Pumps; Sulfoxides
PubMed: 8527612
DOI: 10.1111/j.1365-2036.1995.tb00394.x -
Journal of Clinical Gastroenterology Aug 2003Health-related quality of life (HRQoL) is impaired in untreated patients with gastroesophageal reflux disease (GERD). In the absence of an objective marker such as... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Health-related quality of life (HRQoL) is impaired in untreated patients with gastroesophageal reflux disease (GERD). In the absence of an objective marker such as erosions, assessment of treatment efficacy can be based on symptoms and HRQoL.
OBJECTIVE
To evaluate changes in HRQoL during treatment with pantoprazole or nizatidine in patients with GERD.
METHODS
This was a prospective, randomized, double blind Canadian multicenter study. Patients with GERD, characterized by heartburn that had occurred 4 or more times per week for at least 6 months, were treated for 28 days with either pantoprazole 40 mg once daily or nizatidine 150 mg twice daily. HRQoL assessment was performed before endoscopy (baseline) and on days 7 and 28 after treatment. HRQoL was assessed using 4 domains of the SF-36, the SF-12 summary scales and the gastrointestinal system rating scale (GSRS).
RESULTS
A total of 208 patients (n = 106 pantoprazole treatment group, n = 102 nizatidine treatment group) was available for intention-to-treat analysis. Baseline HRQoL scores were comparable between the 2 treatment groups. After 7 days, treatment with pantoprazole led to a statistically significant greater improvement in HRQoL in 2 SF-36 domains: bodily pain (pantoprazole versus nizatidine, P = 0.0088) and vitality (pantoprazole versus nizatidine, P = 0.0137), and in the GSRS reflux score (pantoprazole versus nizatidine, P = 0.0078). After 28 days of treatment, the changes in scores relative to baseline were still greater with pantoprazole than with nizatidine. The improvement in the 4 SF-36 domains and the GSRS reflux score achieved by pantoprazole after 7 days were also significantly greater than those achieved by nizatidine after 28 days.
CONCLUSIONS
HRQoL improves more rapidly and to a greater degree following treatment with pantoprazole than nizatidine. Control of heartburn strongly predicts HRQoL improvement during the acute treatment of GERD. Our data support the approach to use pantoprazole instead of nizatidine as the initial therapy for patients with heartburn in a primary care practice setting.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Gastroesophageal Reflux; Health Status Indicators; Heartburn; Humans; Nizatidine; Omeprazole; Pantoprazole; Quality of Life; Sulfoxides; Treatment Outcome
PubMed: 12869883
DOI: 10.1097/00004836-200308000-00008