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Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial.
Kitagawa, J, Kobayashi, R, Nagata, Y, Kasahara, S, Ono, T, Sawada, M, Ohata, K, Kato-Hayashi, H, Hayashi, H, Shimizu, M, et al
International journal of cancer. 2021;(6):1462-1469
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Abstract
Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.
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The impact of a 1-hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure.
Krens, SD, Lubberman, FJE, van Egmond, M, Jansman, FGA, Burger, DM, Hamberg, P, Vervenne, WL, Gelderblom, H, van der Graaf, WTA, Desar, IME, et al
International journal of cancer. 2021;(11):2799-2806
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Abstract
Co-treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH-dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1-hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady-state pazopanib trough concentration (Cmin ) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) Cmin levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM Cmin levels were lower in GAS users vs non-GAS users for both the 800 and 600 mg cohorts (23.7 mg/L [95% confidence interval [CI]: 21.1-26.7] vs 28.2 mg/L [95% CI: 25.9-30.5], P = .015 and 26.0 mg/L [95% CI: 22.4-30.3] vs 33.5 mg/L [95% CI: 30.3-37.1], P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non-GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub-analysis showed lower GM pazopanib Cmin in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non-users. Our research showed that a 1-hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.
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Ginger in patients with active ulcerative colitis: a study protocol for a randomized controlled trial.
Shayesteh, F, Haidari, F, Shayesteh, AA, Mohammadi-Asl, J, Ahmadi-Angali, K
Trials. 2020;(1):278
Abstract
BACKGROUND As a lifetime disorder, ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that affects quality of life and also demands long-term interventions. In spite of considerable side effects and sometimes restricted uses, efficient medications are available for UC treatment. Some in vitro and in vivo examinations have correspondingly introduced ginger and its active components with antioxidant, anti-inflammatory, and anti-ulcerative properties. Therefore, this trial aims to evaluate the effect of ginger supplementation on patients with active UC. METHODS This study will be a 12-week, double-blind, parallel-group, randomized, controlled trial (RCT) in which 44 patients will be allocated to ginger and placebo groups receiving basic routine treatments plus ginger or placebo capsules, respectively. The primary outcomes are inflammatory markers (TNF-α and hs-CRP) and total antioxidant capacity. DISCUSSION The findings of this trial will provide evidence on the effect of ginger on patients with active UC. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT20190129042552N1. Registered on 21 June 2019.
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Efficacy of quadruple regimen with polaprezinc for gastric Helicobacter pylori infection eradication: protocol for a single-centre, single-blind, non-inferiority, randomised clinical trial.
Wu, D, Sun, Z, Li, T, Tan, Q, Sun, Y, Chen, T, Liu, Y, Li, J, Jiang, H, Yuan, Z, et al
BMJ open. 2020;(11):e037182
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) is the most well-known risk factor for gastric cancer. At present, H. pylori shows varying levels of resistance to different treatments, leading to a lower rate of H. pylori eradication. The aim of this study is to evaluate the efficacy of polaprezinc-containing quadruple therapy (PQT) for the eradication of H. pylori infection and, thus, to provide more evidence to inform the clinical treatment of H. pylori infection in China. METHODS AND ANALYSIS This is a single-centre, single-blind, non-inferiority, randomised controlled trial, enrolling 158 patients with H. pylori infection. Patients are randomised (1:1) to the two groups for a 14-day therapy. Treatment group: PQT (esomeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, polaprezinc 75 mg) two times per day; control group: bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, bismuth potassium citrate 220 mg) two times per day. The primary outcome is the rate of H. pylori eradication. Secondary outcomes are the incidence of adverse events and the gastrointestinal microbiota distribution. The 16S ribosomal RNA (16S rRNA) next-generation sequencing (NGS) is used to evaluate the effect of two different therapies on the distribution of the gastrointestinal microbiota. ETHICS AND DISSEMINATION This study was approved by the Ethics Committee of Sichuan Cancer Center & Hospital (No. SCCHEC-02-2019-015). Any amendment to the research protocol will be submitted for ethical approval. All participants must provide informed consent. On completion, the results of the study will be published in the appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER ChiCTR1900025800; preresults.
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Stress Ulcer Prophylaxis in Critically Ill Children: A Multicenter Observational Study.
Duffett, M, Chan, A, Closs, J, McGloin, R, McKelvie, G, Pong, S, Seto, W, Slaney, H, Vaninetti, G, Vanniyasingam, T
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2020;(2):e107-e113
Abstract
OBJECTIVE To describe current stress ulcer prophylaxis practice in Canadian PICUs. DESIGN Multicenter cohort study. We defined stress ulcer prophylaxis as the use of a proton-pump inhibitor, histamine-2 receptor antagonist, or sucralfate within the first 2 PICU days among children who had not been on these medications at home and had no evidence of gastrointestinal bleeding. SETTING Seven PICUs in Canada. PATIENTS Three hundred seventy-eight children requiring mechanical ventilation. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Children were ventilated for a median (interquartile range) of 2 days (1-6 d) and stayed in the PICU for a median (interquartile range) of 4 days (2-10 d). The median (interquartile range) age was 1.3 years (0.3-6.7 yr). Seventy percent of all children received acid suppression during their PICU stay. One hundred sixty-seven (54%) of the 309 children eligible for stress ulcer prophylaxis received it. Histamine-2 receptor antagonists were the most frequently used class (66%), followed by proton-pump inhibitors (47%) and sucralfate (4%), and 20% received more than one class. Stress ulcer prophylaxis was continued on the PICU transfer orders for 34% of these children. Children who received prophylaxis were older and had a higher Pediatric Risk of Mortality III score, more often received nonsteroidal anti-inflammatory drugs and systemic corticosteroids and received less enteral nutrition. In multivariate analysis, age and invasive mechanical ventilation were independently associated with an increased likelihood of receiving stress ulcer prophylaxis and receiving feeds was independently associated with a decreased likelihood of receiving stress ulcer prophylaxis. Gastrointestinal bleeding was reported in 21 (6%) of 378 children; three (0.8%) were clinically important. Eighteen percent were treated for a new respiratory tract infection, and 1% developed Clostridium difficile-associated diarrhea. CONCLUSIONS Stress ulcer prophylaxis is common in Canadian PICUs. Clinically important gastrointestinal bleeding and C. difficile-associated diarrhea are rare, and the utility of routine prophylaxis should be examined.
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Effects of oral/enteral nutrition alone versus plus pantoprazole on gastrointestinal bleeding in critically ill patients with low risk factor: a multicenter, randomized controlled trial.
Gündoğan, K, Karakoc, E, Teke, T, Zerman, A, Esmaoglu, A, Temel, Ş, Güven, M, Sungur, M
Turkish journal of medical sciences. 2020;(4):776-783
Abstract
BACKGROUND/AIM: Critically ill patients are at risk of developing gastrointestinal (GI) bleeding due to stress causing mucosal damage. Aim of the study was to determine the effect of oral/enteral nutrition with or without concomitant pantoprazole on upper GI bleeding in low risk critically ill patients. MATERIALS AND METHODS This was a prospective, randomized, open-label, multicenter study conducted with intensive care unit (ICU) patients receiving oral/enteral nutritional support. Patients were randomly assigned into two groups including intervention group (received oral/EN plus pantoprazole) and control group (received only oral/EN). RESULTS A total of 300 patients (intervention group: 152, control group: 148) participated in the study. Overall, 226 (75%) patients were fed by orally and 74 (25%) patients fed by enteral tube feeding. Median duration of nutritional support 4 (range: 2–33) days. Overt upper GI bleeding was noted only in one patient (0.65%) who was in the intervention group. The overall length of ICU stay of 4 (2–105) days, while ICU stay was significantly longer in the intervention group than in the control group (P = 0.006). CONCLUSIONS Our findings seems to indicate that in patients who are at low risk for GI bleeding and under oral/enteral nutritional support, the use of PPIs may not reduce the risk of bleeding, however these results are imprecise because of low event (GI bleeding) rate and limited power.
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Comparison of efficacy of pharmacological therapies for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and network meta-analysis.
Gao, H, Li, L, Zhang, C, Tu, J, Geng, X, Wang, J, Zhou, X, Jing, J, Pan, W
Expert review of gastroenterology & hepatology. 2020;(3):207-220
Abstract
Objectives: This study aimed to compare the efficacy of various anti-ulcer medications in preventing delayed bleeding and promoting ulcer healing after ESD.Methods: Asystematic search was conducted for articles up to August2019. The treatments of iatrogenic ulcer were analyzed by Bayesian network meta-analysis.Results: The analysis included 28 studies. Six treatments were compared. For the prevention of delayed bleeding, potassium-competitive acid blocker (P-CAB) alone was superior to proton-pump inhibitor (PPI) alone [RR = 1.02, 95%CI (1.00, 1.05)]. Treatments based on P-CAB tended to be better than the non-P-CAB groups [RR = 1.05, 95%CI (1.03, 1.07)]. Concerning the ulcer healing rate at 4 weeks, the combined treatment of PPI and mucoprotective agent (MP) was superior to PPI alone [RR = 1.81, 95%CI (1.19, 2.76)] and P-CAB alone [RR = 2.75, 95%CI (1.02, 7.44)]. At 8 weeks, PPI+MP and P-CAB+MP tend to be superior to than the other four groups. The healing effect of MP-based therapies was better than that of non-MP groups at 4 weeks [RR = 1.63, 95%CI (1.32, 2.01)] and 8 weeks [RR = 1.06, 95%CI (1.02, 1.11)].Conclusion: P-CAB may prevent delayed bleeding, but not significantly. MP agents have the potential to heal post-ESD ulcers.
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The combination of wheat peptides and fucoidan protects against chronic superficial gastritis and alters gut microbiota: a double-blinded, placebo-controlled study.
Kan, J, Cheng, J, Xu, L, Hood, M, Zhong, D, Cheng, M, Liu, Y, Chen, L, Du, J
European journal of nutrition. 2020;(4):1655-1666
Abstract
PURPOSE Chronic gastritis is observed in almost half world population. Traditional medications against chronic gastritis might produce adverse effects, so alternative nutritional strategies are needed to prevent the aggravation of gastric mucosal damage. The aim of this study is to evaluate the protective effect of the combination of wheat peptides and fucoidan (WPF) on adults diagnosed with chronic superficial gastritis in a randomized, double-blind, placebo-controlled clinical trial. METHODS Participants were randomized to receive WPF (N = 53) or placebo (N = 53) once daily for 45 days. Pathological grading of gastric mucosal damage was scored using gastroscopy. Fecal samples were collected for the determination of calprotectin, short chain fatty acids (SCFA) levels and metagenomics analysis. Questionnaires for self-reported gastrointestinal discomforts, life quality and food frequency were collected throughout the study. RESULTS WPF intervention reduced gastric mucosal damage in 70% subjects (P < 0.001). Significantly less stomach pain (P < 0.001), belching (P = 0.028), bloating (P < 0.001), acid reflux (P < 0.001), loss of appetite (P = 0.021), increased food intake (P = 0.020), and promoted life quality (P = 0.014) were reported in the WPF group. WPF intervention significantly decreased fecal calprotectin level (P = 0.003) while slightly increased fecal SCFAs level (P = 0.092). In addition, we found altered microbiota composition post-intervention with increased Bifidobacterium pseudocatenulatum (P = 0.032), Eubacterium siraeum (P = 0.036), Bacteroides intestinalis (P = 0.024) and decreased Prevotella copri (P = 0.055). CONCLUSIONS WPF intervention could be utilized as a nutritional alternative to mitigate the progression of chronic gastritis. Furthermore, WPF played an important role in altering gut microbial profile and SCFA production, which might benefit the lower gastrointestinal tract.
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Comparative efficacy of various anti-ulcer medications after gastric endoscopic submucosal dissection: a systematic review and network meta-analysis.
Kim, EH, Park, SW, Nam, E, Lee, JG, Park, CH
Surgical endoscopy. 2019;(4):1271-1283
Abstract
BACKGROUND The comparative efficacy of various anti-ulcer medications after gastric endoscopic submucosal dissection (ESD) has not been fully evaluated. Recently, vonoprazan, a novel potassium-competitive acid blocker, has also been used in ulcer treatment after ESD. METHODS We searched for all relevant randomized controlled trials examining the efficacy of anti-ulcer medications after gastric ESD, published through October 2017. Healing of iatrogenic ulcers was investigated at 4-8 weeks after ESD. A network meta-analysis was performed to calculate the network estimates. RESULTS Twenty-one studies with 2005 patients were included. Concerning the comparative efficacy for ulcer healing at 4 weeks after ESD, no network inconsistency was identified (Cochran's Q-test, df = 10, P = 0.13; I2 = 34%). A combination therapy of proton-pump inhibitor (PPI) and muco-protective agent was superior to PPI alone [risk ratio (RR) (95% confidence interval, CI) 1.69 (1.20-2.39)]. The combination therapy of PPI and muco-protective agents tended to be superior to vonoprazan [RR (95% CI) 1.98 (0.99-3.94)]. There was no difference of ulcer healing effect between PPI and vonoprazan [RR (95% CI) PPI vs. vonoprazan, 1.17 (0.64-2.12)]. Concerning the ulcer healing rate at 8 weeks after ESD, however, vonoprazan was superior to PPI [RR (95% CI) 1.27 (1.03-1.56)]. Additionally, vonoprazan tended to be superior to the combination therapy of PPI and muco-protective agent [RR (95% CI) 1.20 (0.96-1.51)]. CONCLUSIONS A combination therapy of PPI and muco-protective agent was superior to PPI alone for ulcer healing at 4 weeks after ESD. In the ulcer healing effect at 8 weeks after ESD, vonoprazan was superior to PPI.
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Two placebo-controlled crossover studies in healthy subjects to evaluate gastric acid neutralization by an alginate-antacid formulation (Gaviscon Double Action).
Wilkinson, J, Abd-Elaziz, K, den Daas, I, Wemer, J, van Haastert, M, Hodgkinson, V, Foster, M, Coyle, C
Drug development and industrial pharmacy. 2019;(3):430-438
Abstract
OBJECTIVE To investigate the intragastric acid neutralization activity of a combined alginate-antacid formulation. SIGNIFICANCE Published studies have investigated the reflux-suppressing alginate component of Gaviscon Double Action (Gaviscon DA; RB, UK) but intragastric acid neutralization activity of the antacid component has not been evaluated in vivo. METHODS Intragastric pH monitoring, using a custom-made 10-electrode catheter, was evaluated in a two-part exploratory study in healthy subjects; Part I (n = 6) tested suitability of the catheter using antacid tablets (Rennie; Bayer, Germany); Part II (n = 12) evaluated gastric acid neutralization activity of Gaviscon DA liquid (20 ml) versus placebo in fasted subjects using a randomized, open-label, crossover design. The primary endpoint was the percentage of time that intragastric pH ≥4 was measured during 30 min post-treatment. A confirmatory study of identical design was subsequently conducted (n = 20). RESULTS Monitoring pH using the multielectrode catheter was a viable approach, directly detecting changes in intragastric pH following a single dose of antacid tablets. In the exploratory study, the percentage of time that pH ≥4 during 30 minutes post-treatment was 46.8% with Gaviscon DA liquid versus 4.7% with placebo (p = 0.0004). These findings were supported by the confirmatory study, where pH ≥4 was recorded 50.8% of the time with Gaviscon DA versus 3.5% with placebo (p = 0.0051). In this study, Gaviscon DA was safe and well tolerated. CONCLUSIONS These studies demonstrate the effective acid neutralizing capacity of Gaviscon DA versus placebo in healthy, fasted subjects. This adds to the evidence base for the combination of alginates and antacids.