Pantoprazole Group Research Articles

A Clinical Study on the Efficacy and Safety of Poly-Herbal Formulation in Managing Functional Dyspepsia

IntroductionFunctional dyspepsia is a common condition that affects millions of people worldwide. It is characterized by symptoms such as abdominal discomfort, bloating, and nausea, which can significantly impact a person's quality of life. While there are several pharmaceutical treatments available, many individuals are turning to herbal remedies as a safer and more natural alternative. This clinical study aimed to evaluate the efficacy and safety of poly-herbal formulation (PHF), marketed under brand names like Dizester® Herbal, Great Day®, etc. in patients suffering from functional dyspepsia compared to Pantoprazole, a commonly used pharmaceutical treatment. Materials & MethodsThe study included 80 patients, with 40 patients in each treatment arm. The primary objective was to assess the improvement in symptoms using various questionnaires at All India Institute of Medical Science Bhubaneswar, including the Reflux Disease Questionnaire, Short-Form Leeds Dyspepsia Questionnaire, GERD-Health Related Quality of Life Questionnaire, visual analogue scale (VAS) for pain, and Investigator's Symptomatic Assessment. The secondary objective was to evaluate the safety of PHF by assessing liver and renal function parameters and hemogram. Results & discussionThe results showed significant improvement in symptoms of GERD in the PHF group, which was comparable to the Pantoprazole group. The burning feeling behind the breastbone, pain behind the breastbone, burning feeling in the center of the upper stomach, acid taste in the mouth, and unpleasant movement of material upwards towards the mouth improved significantly from the beginning of the study to the follow-up visits. The mean VAS score reduced by 71.5% in the PHF arm and 67.85% in the Pantoprazole arm. Additionally, the study found no abnormal elevations in liver and renal function parameters in blood or any abnormal changes in hemogram, indicating the safety for use in patients with functional dyspepsia. Since the synthetic anti-dyspeptic drugs like proton pump inhibitors are known to have adverse effects, this natural alternative PHF shows promising results in a safer way. ConclusionIn conclusion, this study provides evidence for the efficacy and safety of PHF in improving symptoms of functional dyspepsia. The use of synthetic anti-dyspeptic medications has been associated with the occurrence of undesirable effects. In light of this, PHF has demonstrated encouraging outcomes in a manner that is considered safer.

Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation

BackgroundWhether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear.MethodsIn this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding.ResultsA total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P=0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups.ConclusionsAmong patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.)

Dose-dependent protective effects of Lactobacillus rhamnosus GG against stress-induced ulcer.

Stress-related diseases are on the rise and stress is one of the common factors that lead to ulcer. Stress-induced mucosal bleeding is a serious complication observed in many critically ill patients. Due to the harmful side effects of proton pump inhibitors, natural and active alternative treatment methods for peptic ulcer treatment that are safe in terms of side effects are an urgent need for human health. We aimed to investigate the dose-dependent protective effects of Lactobacillus rhamnosus GG (LGG) against stress ulcer induced by cold restraint stress in rats. This study was performed in a total of 42 rats, in control group (C), stress group (S), pantoprazole (20 mg kg-1 day-1) group (P), LGG (3 × 108 cfu mL-1 day-1) + stress group (M1), LGG (15 × 108 mL-1 day-1) + stress group (M5) and LGG (30 × 108 mL-1 day-1) + stress group (M10) (each n = 7). Ulceration areas (mm2) were determined quantitatively with ImageJ software. Glucocorticoid, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by ELISA and malondialdehyde levels were determined by spectrophotometric measurement. Histopathological examinations were performed in gastric tissue. Therapeutic dose of LGG increased CAT, SOD and GPx levels; prevented excessive activation of the hypothalamic-pituitary-adrenal axis; reduced ulceration and bleeding in the gastric mucosal layer; and provided stabilization of mast cells. We can suggest that LGG may be beneficial for reducing the negative effects of stress on the body, for protecting against ulcer disease and for reducing or preventing the risk of stress-induced gastrointestinal bleeding in patients staying in intensive care units. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Proton-pump inhibitor-induced bone loss is preventable by concomitant use of a long-acting somatostatin analogue.

Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model. Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis. The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (P<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (P<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group. This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.

Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial

Up-to-datedata about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients. We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL. Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups (P<0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan (P<0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively (P<0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding. Short course of vonoprazan 20mg/day is safe and superior to pantoprazole 40mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.

Effects of the probiotic, Lactobacillus rhamnosus GG, on ulcer pathogenesis, HSP70 stress protein and nitric oxide levels in stress induced ulcer

ABSTRACT Peptic ulcer is a gastric or duodenal mucosal injury; psychological stress may participate in development of the lesions. Heat shock protein-70 (HSP70) is a molecular chaperone that is responsible for cellular healing; it is an early biomarker of cellular damage. Nitric oxide (NO) is an intra- and intercellular messenger in the gastrointestinal system that protects mucosal integrity. Lactobacillus rhamnosus is among the microflora of the intestinal tract; it is resistant to gastric acidity. We investigated the efficacy of L. rhamnosus administration on ulcer pathogenesis, stress protein HSP70 and NO levels in experimental stress induced ulcer. The proton pump inhibitor, pantoprazole, was used for comparison with the gastroprotective effect of the probiotic. We administered 10 mg/kg pantoprazole and L. rhamnosus at doses of 3 × 108 cfu/ml (M1), 15 × 108 cfu/ml (M5), 30 × 108 cfu/ml (M10) to rats according to McFarland-1, McFarland-5, McFarland-10 standards, respectively. Rats were stressed by immobilization at 4 °C, then sacrificed. The pH, amounts of gastric mucus, NO and HSP70 levels were measured and the histological structure of stomach was assessed. We found increased NO levels in the M5 group and increased HSP70 expression in the pantoprazole group. Significant epithelial damage was observed in the stressed groups and minimal epithelial damage was observed in M5 group compared to controls. The probiotic, L. rhamnosus, may be useful for preventing stress induced ulcers.

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.

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. 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. 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 (-0.178weeks [-0.390 to 0.034]). 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.

The effectiveness and cost of lansoprazole and pantoprazole for stress ulcer prophylaxis in intensive care unit

The incidence of bleeding is increased in high risk patients with critical conditions in Intensive Care Unit (ICU). Appropriate prophylaxis medicine is necessary to reduce the incidence of stress ulcer bleeding during hospitalization in ICU which further can minimize the cost of patient care in the ICU. Currently, lansoprazole and pantoprazole are used as a stress ulcers prophylaxis. Nevertheless, there has not been sufficient evidence proving their effectiveness. This study was aimed to compare the effectiveness and cost between iv lansoprazole and iv pantoprazole as a stress ulcer prophylaxis in ICU. In this retrospective observational study, the data were obtained from medical records of all patients admitted to ICU in a District Hospital in Yogyakarta from January 2014 until December 2016. Effectiveness of therapy were obtained from objective data in the medical record by looking at the incidence of major (clinically significant) and minor (overt gastrointestinal) bleeding. Chi-square analysis was performed to analyze the difference of bleeding incidence. The average cost was presented as Expected Monetary Value (EMV), which consisted of the cost of prophylaxis and treatment of bleeding. The difference in average cost was analyzed using independent t-test. A total of 119 patients were included in this study. There were 62 patients in the lansoprazole group and 47 patients in the pantoprazole group. Forty eight patients (77,4%) from lansoprazole group and 35 patients (61,4%) from pantoprazole group did not experience any GI bleeding. There was no statistical difference in the incidence of GI bleeding between the two groups (CI 95%, P-value = 0.057). The EMV of lansoprazole group was higher than pantoprazole group IDR 645.122,57 and IDR 511.629,39 respectively. In conclusion, there was no significant difference regarding the effectiveness between iv lansoprazole and iv pantoprazole as stress ulcer prophylaxis. Costs for the prophylaxis of stress ulcers is lower on the use of pantoprazole compared to lansoprazole.

Study on the Effect of Antiplatelet and Gastric Mucosal Protection of Traditional Chinese Medicine Invigorating Qi and Hemostasis.

BackgroundTo investigate the effects of Chinese herbal medicine in tonifying qi and attaining hemostasis caused by the metabolism of the drug clopidogrel and as a result of platelet and gastric mucosa injury in an ischemia-reperfusion rat model.MethodsA pharmacokinetic model was established to record the drug metabolism parameters of clopidogrel metabolites. Then, absorption of the drug was compared with approaches using the traditional Chinese medicine (TCM) approach of tonifying qi and establishing hemostasis, to using the drug pantoprazole and applying these approaches in combination with clopidogrel. Intragastric administration was performed, and all indicators were tested.ResultsThe area under the curve (AUC; 0–T, 300.342 ± 35.832 mg/L* h; AUC 0–∞, 320.462 ± 40.213 mg/L* h), the plasma peak concentration (30.622 ± 9.917 mg/L*), and the peak time and half-life (7.954 ± 1.121 h) in the clopidogrel and the TCM groups were higher than those in the clopidogrel and pantoprazole groups. In terms of antiplatelet aggregation, compared with model group, the platelet aggregation rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) was significantly decreased by the TCM approach of tonifying qi and stopping bleeding (p < 0.05). The ADP, thromboxane A2, GPII B/Pa-A, CD62P and platelet factor 4 content in the TCM yiqi decoction and hemostasis approach were significantly decreased (p < 0.01). Compared with the clopidogrel group, the gastrin and motilin in the serum, the cyclooxygenase (COX)-1 and prostaglandin E2 in gastric tissue, and expression of vascular endothelial growth factor messenger ribonucleic acid in the serum were all significantly increased using TCM approach to protect against gastric mucosal injury (p < 0.05).ConclusionTCM invigorating qi and hemostasis has an inhibitory effect on platelet activation. It can reduce the local inflammatory reaction at the same time as protecting gastric mucosa.

Effect of proton pump inhibitors on voriconazole concentrations in Chinese patients with malignant hematological diseases.

To evaluate the influence of three proton pump inhibitors (PPIs) on plasma voriconazole (VOR) concentrations and characterize potential drug-drug interactions (DDIs) between VOR and three PPIs (omeprazole, lansoprazole, and pantoprazole) in Chinese patients with malignant hematological diseases. A simple and reliable 2D-HPLC with internal quality control method was used to ensure accurate concentration measurements. A total of 194 patients in this retrospective study were divided into control (N = 59), omeprazole (OME, N = 57), lansoprazole (LAN, N = 26), and pantoprazole (PAN, N = 52) groups for comparison of plasma VOR trough concentrations. To further validate our retrospective analysis of clinical data, we used molecular docking simulation to analyze the binding affinity of PPIs to the cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4) enzymes that areintegral to the metabolism of PPIs and VOR. Our findings indicated that VOR trough concentrations were significantly higher in patient on PPIs compared with those who were not (P = 0.012). Patients on LAN (P < 0.01) or OME (P < 0.05) had significantly elevated VOR concentrations compared with the control group, whereas those on PAN did not. Although VOR trough concentrations were not significantly elevated with PAN, more patients in the PAN group reached therapeutic VOR concentrations than in any other group. In conclusion, our retrospective data analysis and molecular docking simulations results indicate that LAN and OME interact with VOR via CYP2C19 and CYP3A4to increase VOR plasma concentrations. This study helps with selection of PPIs in Chinese patients with malignant hematological cancer administered VOR.

Comparison of Oral versus Intravenous Proton Pump Inhibitors in Preventing Re-bleeding from Peptic Ulcer after Successful Endoscopic Therapy.

IntroductionPerforation, obstruction, and bleeding remain the most frequently encountered complications of peptic ulcer disease (PUD). Bleeding may be in the form of hematemesis or melena. The treatment of choice in patients with a bleeding peptic ulcer is endoscopic ligation to maintain the hemostatic balance followed by the administration of proton pump inhibitors (PPIs). This study focuses on the evaluation and comparison of intravenous (IV) and oral PPIs in terms of prevention of re-bleeding after successful endoscopy for peptic ulcers.MethodsA prospective, comparative study was conducted in a tertiary care hospital in Pakistan from January 1, 2018 to June 30, 2019. The trial included known cases of PUD admitted with active upper gastrointestinal bleeding (UGIB). They were randomly divided into two groups: one received oral pantoprazole and the other was administered IV pantoprazole. The outcomes for both groups were compared. Data was entered and analyzed using Statistical Package for the Social Sciences (SPSS) software version 23.0 (IBM, Armonk, NY)ResultsThere were 96 (48%) patients in the IV pantoprazole group and 104 (52%) in the oral group. From 24 hours after the medication onwards, the IV pantoprazole group showed a significant improvement in hemoglobin (Hb) levels (p: 0.01); the group also showed improvement in supine systolic BP at 48 hours (p: 0.04) and in diastolic BP at both 12 and 48 hours as compared to the oral pantoprazole group (p: 0.05). The mean duration of hospital stay, need for blood transfusion and repeat endoscopy, re-bleeding, and mortality rates were similar for both groups (p: >0.05).ConclusionWe could not find any statistically significant difference between oral and IV routes of pantoprazole administration in the prevention of rebleeding when used after successful therapeutic endoscopy in patients with bleeding PUDs.

Comparison of Intra-Venus Ranitidine with Pantoprazole in Patients with Epigastric Pain Referring to Emergency Department

Background and aim: Epigastric pain episodes are one of the most common complaints of patients referring to the emergency departments worldwide. The purpose of this study was to compare the effects of ranitidine and pantoprazole on epigastric pain in the emergency department. Materials and Methods: This randomized clinical trial (RCT) study was performed on 100 patients (50 patients in each study arm) with epigastric pain complaints referred to emergency department of Imam Khomeini Educational Hospital in Sari in 2017. Patients older than 18 years of age with an epigastric pain with early diagnosis of dyspepsia and a visual acuity score of 20 mm high (VAS) were included. Patients were enrolled in two treatment groups: single venous dose of pantoprazole 40 mg and single dose of ranitidine 50 mg. The pain score was recorded 30 and 60 minutes after the intervention. Results: The findings showed that in the pantoprazole group: 9.4% dyspepsia and 37.5% pancreatitis and 12.5% gastroenteritis and 40.6% asymptomatic. Before the intervention, the pain group had a pain score of 10.8 and 8.16 in the pantoprazole group. There were no differences between the two groups (P = 0.888), but after treatment, significant difference were observed in each of the groups after the use (P<0.001). Also, the comparison of the two groups after treatment showed that there was a significant difference in pain severity between the two treatment groups (P<0.001). Conclusion: The results of this study have revealed that Ranitidine and Pantoprazole effectively improve initial epigastric pain, but ranitidine is more effective.

Highlights from the literature

The Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) study, published in the New England Journal of Medicine , evaluated the use of prophylactic pantoprazole in patients at risk...

Highlights from the literature

The Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) study, published in the New England Journal of Medicine , evaluated the use of prophylactic pantoprazole in patients at risk...

Intravenous esomeprazole versus pantoprazole for heartburn

Heartburn is one of the most common symptoms of gastrointestinal diseases. Intravenous (IV) administration of pantoprazole, lansoprazole, and esomeprazole is recommended by the US Food and Drug Administration (FDA) for short-term acute treatment. Although there are many studies on these drugs in the literature, they are frequently related to long-term oral use and changes in intragastric pH. This study compared the effects of IV esomeprazole with those of IV pantoprazole in patients presenting to the emergency department with heartburn. For this randomized controlled double-blind trial, patients aged over 18 years presenting with gastritis-related heartburn were eligible. Study patients received 40 mg esomeprazole or pantoprazole in 100 ml normal saline. Pain intensity was measured on a visual analog scale (VAS) at 30, 60, and 120 min. Patients were randomized and assigned to either of the two study arms via closed envelopes. Finally, 205 patients were randomized (esomeprazole: 104; pantoprazole 101). Mean age was 39.1 ± 13.78 years and 48.8% were male. Both esomeprazole (median VAS: 26 mm, interquartile range [IQR]: 17–38 mm) and pantoprazole (median: 24 mm, IQR: 14.5–36 mm) effectively reduced heartburn at 30 min, 60 min (median: 59.5 mm, IQR: 48–73.5 mm vs. 55 mm, IQR: 33–68.5 mm), and 120 min (median: 80 mm, IQR: 66.5–89.8 mm vs. 77 mm, IQR: 56–85 mm). While there was no statistically significant difference between the two drugs at 30 min (p = 0.312), there was a statistically significant difference in pain intensity between the esomeprazole and pantoprazole groups at 60 and 120 min (p = 0.014, p = 0.02, respectively). Single-dose slow IV infusion of esomeprazole is faster and more effective in controlling heartburn than pantoprazole.

Pantoprazole in ICU patients at risk for gastrointestinal bleeding-1-year mortality in the SUP-ICU trial.

The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40mg vs placebo (saline) once daily during their ICU stay. We assessed mortality at 1 year and did sensitivity analyses according to the trial protocol and statistical analysis plan. A total of 3261 of the 3291 patients with available data (99.1%) were followed up at 1 year after randomisation; 1635 were allocated to pantoprazole and 1626 to placebo. At 1 year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01; 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole vs placebo on 1-year mortality in the predefined subgroups, that is, patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs surgical ICU patients. We did not observe a difference in 1-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay. (The SUP-ICU trial was funded by Innovation Fund Denmark and others; ClinicalTrials.gov number, NCT02467621).

The Effect of Proton Pump Inhibitors on Bone Formation in a Rat Spinal Arthrodesis Model.

Rat posterolateral arthrodesis model. Quantify the impact of administration of a proton pump inhibitor on spine fusion. Proton pump inhibitors (PPIs) are widely used for gastrointestinal disorders and for ulcer prophylaxis in patients taking non-steroidal anti-inflammatory drugs. PPIs cause chronic acid suppression which has been found to result in decreased bone mineral density, increased fracture risk, and impaired fracture healing. Despite advances in surgical techniques, pseudarthrosis still occurs in up to 24% of patients requiring revision surgery following spinal fusion procedures. Thus, there are likely many unidentified risk factors. While PPIs have been hypothesized to impact fracture healing, no study has evaluated their effect on spine arthrodesis rates. Thirty-eight female rats underwent posterolateral lumbar spinal fusion. Rats were divided into two groups: normal saline control and pantroprazole, which was administered by daily intraperitoneal injections. At 8 weeks postoperative spines were evaluated with manual palpation, microCT, histologic analysis, and biomechanical testing. Fusion rates of the control group and PPI group were not significantly different (100% vs. 94%). Average fusion scores were significantly lower in the pantoprazole group. New bone formation identified on microCT imaging of bilaterally fused specimens demonstrated a lower average volume of newly generated bone in the PPI group, but this difference was not significant. Biomechanical testing demonstrated no significant difference in strength or stiffness of the fusion mass between the groups. This study demonstrates that administration of PPIs does not inhibit fusion rates, bone formation, or affect biomechanical integrity of fusion. However, lower fusion scores in the PPI group suggest that a negative impact may still exist. Future studies will explore growth factor and protein expression in the fusion masses as well as utilize higher doses of PPI to fully discern their effect on spine fusion. N/A.

Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial.

Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. We performed a 3× 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P= .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n= 982; 95% confidence interval, 609-2528). In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

Pantoprazole reduces serum ferritin in patients with thalassemia major and intermedia: A randomized, controlled study

Complications due to iron overload exert a problematic situation in patients with thalassemia. Proton pump inhibitors (PPIs) like pantoprazole are effective agents to reduce acid gastric acid secretion and perhaps to interrupt iron absorption in conditions with increased iron absorption. Our purpose was to study effects of pantoprazole addition to chelators on iron levels in patients with thalassemia major and intermedia. This randomized, controlled, and single center trial was performed on 60 patients with thalassemia major and intermedia in Amir Kabir hospital, Iran. Patients were randomized 1:1 to pantoprazole group (iron chelator plus pantoprazole) or control group (iron chelator) for 6 months. Serum ferritin was measured by ELISA. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*. After 6 months of treatment, a significant reduction was seen in serum ferritin levels in the pantoprazole group (1444±613μg/mL to 1197±956μg/mL; P<0.001). A further reduction was seen in patients with thalassmeia intermedia. There were no significant changes in myocardial T2* values in pantoprazole group compared to control group (23.6±7.3ms to 24.1±6.4ms). Compared to the control group, pantoprazole therapy had no effect on hepatic T2* value (9.7±2.3ms to 9.8±2.6ms). However, between-group difference was significant (P<0.05). Pantoprazole therapy for 6 months has benefits for reducing serum ferritin in patients with thalassemia major and intermedia. Pantoprazole addition to iron chelators seems safe.

Effects of esomeprazole and pantoprazole on renal function in stable kidney transplantation recipients: A randomized clinical trial.

Renal allograft survival requires the administration of multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro-protective medications, notably, proton pump inhibitors (PPIs). This study aimed to compare the effects of pantoprazole and esomeprazole on renal function in stable renal transplant recipients. A prospective, parallel, open-label clinical trial was performed with forty-seven adult renal transplant recipients receiving immunosuppressive therapy with cyclosporine (CSA) doses adjusted to attain trough concentrations of 100-150 µg/L, mycophenolate mofetil (MMF) at 750 mg q12 hr and prednisolone at 5 mg daily at Nasser Institute, Cairo, Egypt. The enrolled participants were randomized into two groups, which received either esomeprazole or pantoprazole at the same dose (40 mg once daily). Renal function was measured at baseline and monthly for 6 months. The study was conducted between January-September 2016. Main outcome measures clinical signs of rejection reflected by renal function decline, assessed by elevated levels of serum creatinine. The mean serum creatinine level was significantly lower in the sixth month than at baseline in esomeprazole group (p 0.004); interestingly there was a continuous decrease of serum creatinine levels in esomeprazole group and nearly constant values in pantoprazole group. There was no significant difference in serum creatinine levels between the two groups. From this study, it could be concluded that esomeprazole may be preferred over pantoprazole in renal transplant recipients because it decreased serum creatinine which is one of the markers of chronic allograft rejection in stable renal transplantation recipients.