Pooled Eradication Rates Research Articles

Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials.

This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

Vonoprazan and amoxicillin dual therapy as the first-line treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.

Effectiveness of eradication therapy for Helicobacter pylori infection in Africa: a systematic review and meta-analysis

BackgroundThe effectiveness of Helicobacter pylori (H. pylori) eradication depends on the treatment protocol. This study investigates the H. pylori eradication rate in Africa using the best available evidence from databases.MethodsDatabases were searched and results were pooled together. Heterogeneity between studies was assessed using I2 test statistics. Stata version 13 software was employed to compute the pooled eradication rate. In the subgroup analysis comparison, the finding is considered significant when the confidence intervals did not overlap.ResultsTwenty-two studies from 9 African countries with a total population of 2,163 were included in this study. The pooled eradication rate of H. pylori was 79% (95% CI: 75%-82%), heterogeneity (I2 = 93.02%). In the subgroup analysis by study design, a higher eradication rate was reported from observational studies (85%, 95% CI: 79%-90%), compared to randomized control trials (77%, 95% CI: 73%-82%); by the duration of therapy, higher eradication rate was reported in 10-days regimen (88%, 95% CI: 84%-92%), compared to 7-days regimen (66%, 95% CI: 55%-77%); by country, the highest eradication rate was found in Ethiopia (90%; 95% CI: 87%-93%) and the lowest eradication rate was reported in Ivory Coast (22.3%; 95% CI:15%-29%); by type of H. pylori test, the highest eradication rate was reported when rapid urease test coupled with histology (88%, 95% CI: 77%-96%), and the lowest eradication rate was reported with histology alone (22.3%; 95% CI:15%-29%). Significant heterogeneity was observed with pooled prevalence (I2 = 93.02%, P < 0.000).ConclusionsIn Africa, the first-line therapy showed a variable eradication rate for H. pylori. This study demonstrates the necessity to optimize current H. pylori treatment regimens in each country, taking into account the antibiotic susceptibility. Future RCT studies with standardized regimens are warranted.

Empirical versus tailored therapy based on genotypic resistance detection for Helicobacter pylori eradication: a systematic review and meta-analysis.

The eradication rate of Helicobacter pylori infection with empirical therapy has decreased due to increased drug resistance. The latest guidelines recommend genotypic resistance-guided therapy, but its clinical efficacy remains unclear. The purpose of our study was to evaluate whether tailored therapy based on genotypic resistance is superior to empirical therapy for H. pylori infection. A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing tailored therapy based on genotypic resistance with empirical therapy was performed. We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate and the adverse events (AEs) was the secondary outcome. A random-effect model was applied to compare pooled risk ratios (RRs) with related 95% confidence intervals (CIs). A total of 12 qualified RCTs containing 3940 patients were identified in our systematic review and meta-analysis. The pooled eradication rates of tailored therapy based on the detection of genotypic resistance were consistently higher than those in the empirical treatment group, with no statistical significance. In triple therapy, the eradication rate was significantly higher in the tailored group than in the empirical group by intention-to-treat analysis (ITT) and per-protocol analysis (PP) analysis (p < 0.0001, RR: 1.20; 95% CI: 1.12-1.29; p < 0.0001, RR: 1.20; 95% CI: 1.15-1.25). In quadruple therapy, the eradication rate was higher in the empirical group (p = 0.001, RR: 0.93; 95% CI: 0.89-0.97; p = 0.009, RR: 0.95; 95% CI: 0.92-0.99). And this result was true for both bismuth quadruple therapy (BQT) and non-BQT. Regarding total AEs, the pooled rate was 34% in the tailored group and 37% in the empirical group, and no difference between the two groups was found (p = 0.17, RR: 0.88; 95% CI: 0.74-1.06). In conclusion, tailored therapy based on molecular methods may offer better efficacy than empirical triple therapy, but it may not be superior to empirical quadruple therapy in eradicating H. pylori infection. Larger and more individualized RCTs are needed to aid clinical decision-making. CRD42023408688.

A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis.

Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta-analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid-related diseases. We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings. Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H.pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. Vonoprazan is superior to PPI in first-line H.pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.

Efficacy of bismuth for antibiotic-resistant Helicobacter pylori strains eradication: A systematic review and meta-analysis.

Antibiotic resistance of Helicobacter pylori (H.pylori) is increasing worldwide, and bismuth quadruple therapy has been recommended as a first-line regimen in many areas. This study aimed to investigate whether bismuth would improve the eradication rate (ER) of clarithromycin-/metronidazole-/levofloxacin-resistant H.pylori strains and how much additional efficacy bismuth could achieve. PubMed, EMBASE, Web of Science, and Cochrane Central databases for randomized controlled trials were systematically searched by two independent reviewers until 15 January 2022. Pooled ERs of clarithromycin-/metronidazole-/levofloxacin-resistant H.pylori strains were compared between bismuth-containing and non-bismuth therapies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Eight studies enrolling 340 individuals were included. The RRs of pooled ERs compared between bismuth-containing and non-bismuth therapies were 1.83 for clarithromycin-resistant strains (95% CI 1.16-2.89, pooled ER: 76.9% vs. 36.6%, p=.009, I2 =0%), 1.39 for metronidazole-resistant strains (95% CI 1.09-1.78, pooled ER: 86.8% vs. 60.9%, p=.008, I2 =37%), 2.75 for dual clarithromycin/metronidazole-resistant strains (95% CI 1.01-7.52, pooled ER: 76.9% vs. 18.2%, p=.05, I2 =0%), and 1.04 for levofloxacin-resistant strains (95% CI 0.56-1.93, pooled ER: 63.4% vs. 54.3%, p=.90; I2 =60%). Bismuth significantly increased the ERs of clarithromycin-, metronidazole-, and dual-resistant strains by 40%, 26%, and 59%, respectively. Subgroup analysis of treatment duration showed that the significantly higher eradication rate for antibiotic-resistant strains in bismuth-containing therapy than non-bismuth therapy was only observed in 14-day treatment regimens and not in 7-day regimens (p=.02 and .17, respectively). Bismuth was most effective in improving the ERs of dual-resistant H.pylori strains, followed by clarithromycin- and metronidazole-resistant strains. Prolonged treatment duration might effectively improve the efficacy of bismuth in overcoming antibiotic resistance.

Susceptibility testing alone will not reliably achieve high Helicobacter pylori cure rates: A systematic review and meta-analysis.

Not all the susceptibility-guided therapies for Helicobacter pylori (H.pylori) infection achieve excellent eradication rates. The aim of this study was to perform a systematic review and meta-analysis to identify the optimal regimen for H.pylori treatment based on antibiotic susceptibility. A systematic search was performed in multiple databases. Studies reporting eradication rates of H.pylori with susceptibility-guided therapies were selected. Meta-analysis was conducted to calculate the pooled eradication rate among the treatment regimens. Forty-eight eligible studies with 101 susceptibility-guided treatment arms were included. The overall eradication rate in patients harboring susceptible strains was 95.0% (95% CI, 94.1-95.9%), but only 63.4% of treatment arms (64/101) achieved good eradication rates (≥90%). Pooled eradication rates in patients with susceptible strains were: 93.4% (95% CI, 92.0-94.8%) for clarithromycin, 99.0% (95% CI, 98.1-100%) for nitroimidazoles and 95.4% (95% CI, 93.6-97.2%) for fluoroquinolones. Among the arms using a triple therapy, 66.7% (28/42) using clarithromycin, 84.2% (16/19) using nitroimidazoles and 70.8% (17/24) using fluoroquinolones achieved good (≥90%) eradication rates. Of 13 arms using sequential therapy, ≥90% eradication was achieved in 14.3% (1/7) using clarithromycin, 25.0% (1/4) using nitroimidazoles and both arms (2/2) using fluoroquinolones. Susceptibility testing alone seemed insufficient to reliably attain high H.pylori cure rates. The eradication rate in patients with nitroimidazoles susceptible strains was higher than those of fluoroquinolones and clarithromycin.

Susceptibility-Guided Therapy vs. Bismuth-Containing Quadruple Therapy as the First-Line Treatment for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

BackgroundThe increased antibiotic resistance of Helicobacter pylori (H. pylori) has led to the decreased efficacy of H. pylori regimens.AimTo evaluate the efficacy, safety, and compliance of susceptibility-guided therapy (SGT) vs. bismuth-containing quadruple therapy (BQT) as the first-line treatment for H. pylori infection.Materials and MethodsThis meta-analysis was performed in accordance with the PRISMA 2009 guidelines. A systematic search in PubMed, Embase, and Cochrane databases was conducted using the combination of “H. pylori or H. pylori or Hp,” “bismuth quadruple,” and “tailored eradication OR tailored therapy OR susceptibility-guided therapy OR personalized therapy OR antibiotic susceptibility testing.”ResultsFive studies with 2,110 H. pylori-infected patients were enrolled. The pooled eradication rates of SGT and BQT were 86 vs. 78% (p < 0.05) and 92 vs. 86% (p > 0.05) by intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. SGT has a significantly superior efficacy than BQT [pooled risk ratio (RR) = 1.14, p < 0.05] in a subgroup of cultures with the susceptibility test. The pooled side effect rate was 20% in SGT and 22% in BQT, which showed no significant difference (p > 0.05). The compliances of SGT and BQT were 95 and 92%, respectively.ConclusionCompared with BQT, SGT showed a higher efficacy and similar safety as the first-line treatment of H. pylori infection in areas with high antibiotic resistance. The decision-making of first-line regimens for H. pylori infection should depend on the availability and cost-effectiveness of susceptibility tests and bismuth in local areas.

Worldwide and Regional Efficacy Estimates of First-line Helicobacter pylori Treatments: A Systematic Review and Network Meta-Analysis.

Eradication of Helicobacter pylori infection is challenging. We aimed to determine the optimal first-line H. pylori treatments at global and regional levels. We searched Embase, PubMed, Cochrane CENTRAL, Web of Science, Scopus, WHO ICTRP, ClinicalTrials.gov, and ISRCTN registry, for randomized controlled trials published during 2011-2020. Utilizing a network meta-analysis in a Bayesian framework, success rates of 23 regimens were compared. The effect size was standardized risk ratio (RR) with 95% credible interval (CrI). Pooled eradication rate (ER) with 95% CrI was also reported for top combinations. The reference regimen was 7-day clarithromycin-based triple therapy. This review identified 121 trials comprising 34,759 participants. Globally, 14-day levofloxacin-based sequential therapy was the most efficient (RR: 1.43; 95% CrI, 1.26-1.59) with low certainty of evidence, followed by modified bismuth-containing quadruple therapy (proton pump inhibitor+bismuth compounds+clarithromycin+amoxicillin) for 10 days (RR: 1.35; 95% CrI, 1.22-1.48) and 14 days (RR: 1.27; 95% CrI, 1.12-1.42), and 14-day hybrid therapy (RR: 1.27; 95% CrI, 1.19-1.36). The corresponding ERs were 98.7% (95% CrI, 86.9-100.0), 93.2% (95% CrI, 84.2-100.0), 87.6% (95% CrI, 82.1-93.8), and 87.6% (95% CrI, 77.3-98.0), respectively. Continentally, the most effective combinations were: 10-day clarithromycin-based sequential therapy [(RR: 1.21; 95% CrI, 1.02-1.42), (ER: 89.5%, 95% CrI, 75.5-100.0)] for Africa, 14-day levofloxacin-based sequential therapy [(RR: 1.41; 95%CrI, 1.27-1.58), (ER: 98.7%, 95% CrI, 88.9-100.0)] for Asia, and 14-day clarithromycin-based triple therapy [(RR: 1.58; 95% CrI, 1.25-2.04), (ER: 94.8%; 95% CrI, 75.0-100.0)] for Europe. For Northern America, no sufficient data were found for network meta-analysis. In South America, none of the combinations were superior to the reference regimen. Although results of this network meta-analysis revealed optimal combinations for empiric therapy, the treatment preference would be based on the local pattern of antibacterial resistance, when the necessary information exists.

Doxycycline and minocycline in Helicobacter pylori treatment: A systematic review and meta-analysis.

The decreasing Helicobacter pylori eradication rate and the increasing antibiotic resistance trend are of great concern. Therefore, new and effective therapies are needed for H.pylori infection. We conducted a systematic review and meta-analysis to assess the efficacy and safety of semisynthetic tetracycline regimens in H.pylori treatment. PubMed, EMBASE, and the Cochrane library were searched. The outcome indicators were the eradication rate, risk ratio (RR, ie, the risk of the semisynthetic tetracycline regimen relative to the control), and 95% confidence interval (95% CI). Controls were patients undergoing any other treatment without semisynthetic tetracycline. Twenty-three studies with 5240 participants were included. The eradication rates of triple regimens with semisynthetic tetracyclines in most studies were less than 70% in both the intention-to-treat (ITT) and the per-protocol (PP) analyses. The pooled eradication rates of quadruple therapies with doxycycline and controls were 95% and 84% in the PP analyses, respectively. The pooled RR associated with efficacy in the quadruple therapy with doxycycline group compared with the control group was 1.12 (95% CI: 1.04-1.20) in the PP analysis. The pooled RR of side effects in the quadruple therapy with doxycycline group compared with the control group was 1.01 (95% CI: 0.65-1.55). Seven-day and ten-day quadruple therapy with doxycycline might be an optional first-line therapy. The safety of regimens containing semisynthetic tetracyclines was relatively satisfactory. However, the triple regimen is not recommended.

Eradication Rates of Clarithromycin Triple Therapy in Korea: A Systematic Review and Meta-analysis

Background/Aims: Standard triple therapy, including a proton pump inhibitor, clarithromycin, and amoxicillin, has been recommended as the first-line for &lt;i&gt;Helicobacter pylori&lt;/i&gt; infection. However, the eradication rate of standard triple therapy has declined over the past years because of the increasing resistance to clarithromycin in Korea. We analyzed the eradication rates and the 10-year change in the eradication rates in Korea.Methods: PubMed, EMBASE, the Cochrane Library, and KoreaMed were searched for studies published between January 2007 and June 2018. The pooled eradication rates and their 95% CIs were estimated using a random-effect logistic regression model.Results: Twenty-six randomized controlled studies on standard triple therapy conducted in Korea were selected. The intention-to-treat (ITT) and per protocol analyses showed pooled eradication rates of standard triple therapy of 71.6% (95% CI, 69.9~73.3%) and 79.6% (95% CI, 76.6~82.2%), respectively. The eradication rate decreased with time. The ITT analysis showed that the 14-day therapy (78.1% [95% CI, 75.2~80.7%]) had significantly higher eradication rates than the 7-day therapy (70.0% [95% CI, 68.5~71.4%]) (&lt;i&gt;P&lt;/i&gt;&lt;0.01).Conclusions: These results suggest that the eradication rate of standard triple therapy, as the first-line therapy, has shown an unacceptable decrease. The eradication rate increased when the duration of therapy was increased to 14 days, but it was not satisfactory. Therefore, other treatment regimens or therapies based on susceptibility tests should be considered for the first-line therapy.

A 10- or 14-day Bismuth-containing Quadruple Therapy as a First-line Helicobacter pylori Eradication Therapy: A Systematic Review and Meta-analysis

Background/Aims: The eradication rate of the first-line standard triple therapy (STT) for &lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) infection has decreased since 2000; therefore, other first-line therapies are required. This study was aimed at investigating the efficacy of bismuth-containing quadruple therapy (PBMT) for first-line &lt;i&gt;H. pylori&lt;/i&gt; eradication compared to STT, sequential therapy (SQT), and concomitant therapy (CT).Materials and Methods: The Ovid-MEDLINE, Koreamed, EMBASE, KMBASE, and Cochrane Library databases were searched from January 2008 to July 2018. All identified randomized controlled trials (RCTs) comparing PBMT and non-PBMT for first-line &lt;i&gt;H. pylori&lt;/i&gt; eradication therapy were included in the final analysis.Results: A total of 3,653 patients from seven RCTs were enrolled. The pooled eradication rates of PBMT by intention-to-treat (ITT) and per-protocol (PP) analyses were 82.1% (95% CI, 68.2~90.8%) and 88.8% (95% CI, 77.1~94.9%), respectively. However, no statistically significant difference was observed in eradication rates of the 10- or 14-day PBMT as compared to 14-day STT, 10-day SQT, and 10-day CT in ITT and PP analyses. PBMT was significantly higher in adverse events than in the other eradication regimens (RR, 1.64; 95% CI, 1.11~2.44). Considerable heterogeneity in adverse events was observed among studies (χ&lt;sup&gt;2&lt;/sup&gt;=88.7; &lt;i&gt;P&lt;/i&gt;&lt;0.001, I&lt;sup&gt;2&lt;/sup&gt;=93%).Conclusions: PBMT can be the first-line treatment for &lt;i&gt;H. pylori&lt;/i&gt; eradication in Korea when other first-line options, including STT, SQT, or CT, are unavailable due to their high adverse event rates.

Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

BackgroundHelicobacter pylori (HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP.MethodsWe have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP.ResultsThirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%).ConclusionNitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.

1237 Efficacy and Safety of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

INTRODUCTION: Helicobacter pylori (HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy and bismuth-based quadruple therapy are among recommended first-line treatment regimens, but may fail in around 30% of patients. Resistance of HP to clarithromycin and metronidazole is also a growing concern. Therefore, there is a need for newer, reliable eradication regimens for HP. Nitazoxanide (NTZX), a bactericidal thiazolide antibiotic, has been effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of NTZX-based regimens for the eradication of HP. METHODS: We searched several databases from inception to April 2019 to identify studies that used nitazoxanide as part of an HP treatment regimen. We only included patients who completed the full length of therapy and were tested for eradication on follow up. Our primary outcome was the pooled HP eradication rate. We also performed a subgroup analysis to evaluate NTZX-based regimens in patients who had failed prior treatment. Pooled eradication rates and 95% confidence intervals (CIs) were initially calculated as per protocol analysis from the included studies. Publication bias was evaluated by Egger's test. RESULTS: Twelve studies including 978 patients met our inclusion criteria and were included in the meta-analysis. There were 4 randomized controlled trials, 7 prospective cohort studies and 1 retrospective cohort study. 7 studies were of good quality and 5 studies were of fair quality. HP eradication was successful in 826; (pooled eradication rate = 83%; 95% CI 76-90%) without significant heterogeneity (P = 0.17). In a subgroup analysis including 230 patients who had failed other prior regimens, the pooled eradication rate was 80% (95% CI 66-94%) without significant heterogeneity (P = 0.39). No serious adverse events were reported. In a subgroup analysis, the highest eradication rates were with levofloxacin, doxycycline, NTZX and a proton pump inhibitor; pooled eradication rate = 92% (81 -100%). There was no publication bias as evaluated by Egger's test [P = 0.94]. CONCLUSION: NTZX-based regimens appear safe and effective first-line for HP eradication and are also successful as salvage therapy in patients who had failed prior treatments. Larger randomized controlled trials are required to determine the most effective NTZX-based regimen and the optimum duration of therapy for this increasingly multi drug-resistant infection.

Efficacy and Safety of Vonoprazan-Based versus Proton Pump Inhibitor-Based Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Clinical Trials.

Aims To compare the efficacy and safety of vonoprazan-based versus proton pump inhibitor (PPI)-based triple therapy in the eradication of Helicobacter pylori. Methods We performed a systematic search in PubMed, Embase, and the Cochrane Library databases for relevant randomized controlled trials up to March 2019. Studies were included if they compared the efficacy and safety of H. pylori eradication of vonoprazan-based and PPI-based triple therapy. Results Three studies with 897 patients were evaluated in this meta-analysis. The H. pylori eradication rate of vonoprazan-based triple therapy was higher than that of PPI-based triple therapy as first-line regimens (intention-to-treat analysis: pooled eradication rates, 91.4% vs 74.8%; odds ratio [OR], 3.68; 95% confidence interval (CI): [1.87–7.26]; P<0.05). The incidence of adverse events in vonoprazan-based triple therapy was lower than that in PPI-based triple therapy (pooled incidence, 32.7% vs 40.5%; OR, 0.71; 95%CI: [0.53–0.95]; P<0.05). Conclusions Efficacy of vonoprazan-based triple therapy is superior to that of PPI-based triple therapy for first-line H. pylori eradication. Additionally, vonoprazan-based triple therapy is better tolerated than PPI-based triple therapy.

Systematic review and network meta-analysis: Comparative effectiveness of therapies for second-line Helicobacter pylori eradication.

The eradication rate of Helicobacter pylori (H. pylori) has been declining over the past decades. A rescue plan is needed for increasing populations with treatment failure. However, the optimum second-line eradication regimen remains inconclusive. We conducted a network meta-analysis to assess the comparative effectiveness of second-line H. pylori eradication therapies and determine the optimum regimen. We searched electronic databases from January 2005 to February 2018 for randomized controlled trials assessing the effectiveness of second-line regimens in patients with persistent H.pylori infection after first-line treatment. Bayesian network meta-analysis was performed to combine the direct and indirect evidence and to investigate the rank order of second-line therapies. We also appraised the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation guidance. Twenty-six trials with 3628 participants who received second-line eradication therapy were identified. All regimens showed pooled eradication rates <90%. Compared with 7-day triple therapy, quinolone-based (odds ratio [OR] 4.29, 95% credible interval [CrI] 1.67-12.12, surface under the cumulative ranking [SUCRA] 0.95), non-quinolone-based bismuth-containing quadruple therapies for 10days or more (OR 2.25, 95% CrI 1.10-4.62, SUCRA 0.78), and sequential therapy (OR 2.91, 95% CrI 1.16-7.65, SUCRA 0.66) showed significantly higher effectiveness. Overall, regimens with longer duration demonstrated higher eradication rates but higher rates of adverse events. More adverse events were reported in those patients treated with concomitant therapy. Quinolone-based bismuth-containing quadruple therapies for 10days or more are the optimum second-line regimens for H.pylori eradication.

Systematic review with meta-analysis: Vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori.

Vonoprazan is a novel gastric acid suppressant that is applied in Japan to treat gastric diseases including Helicobacter pylori (H.pylori) infection. This meta-analysis aimed to summarize the ability of vonoprazan to eradicate clarithromycin-susceptible and clarithromycin-resistant H.pylori strains. A systematic search was performed using PubMed, EMBASE, Web of Science, and Cochrane Library. Studies were included if they evaluated eradication rates of vonoprazan-based and conventional PPI-based triple therapies and checked for clarithromycin susceptibility of H.pylori. We identified 5 studies including a total of 1599 patients containing data regarding H.pylori with clarithromycin susceptibility. Among those infected with clarithromycin-susceptible H.pylori, eradication rates for vonoprazan-based and conventional PPI-based therapies did not significantly differ in either the randomized (RCT; pooled eradication rates, 95.4% vs 92.8%; pooled odds ratio [OR], 1.63; 95% confidence intervals [CI], 0.74-3.61; P=.225) and nonrandomized (NRCT; pooled eradication rates, 92.9% vs 86.2%; OR, 4.58; 95% CI, 0.67-31.45; P=.122) controlled trials. However, vonoprazan-based triple therapy was significantly superiority to PPI-based therapy for patients with clarithromycin-resistant strains in both RCT (pooled eradication rates, 82.0% vs 40.0%; OR, 6.83; 95% CI, 3.63-12.86; P<.0001) and NRCT (pooled eradication rates, 80.8% vs 41.8%; OR, 4.98; 95% CI, 2.47-10.03; P<.0001). Vonoprazan-based and conventional PPI-based therapies are similarly effective for the eradication of clarithromycin-susceptible H.pylori strains. Vonoprazan is superior to conventional PPI-based therapy for the eradication of clarithromycin-resistant H.pylori strains. However, clarithromycin was misused because the combination of vonoprazan and amoxicillin cures approximately 80% of infections without clarithromycin.

Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis.

AIMTo define probiotic monotherapy effect on Helicobacter pylori (H. pylori) status by performing a systematic review.METHODSMethods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching PubMed, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios (ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo.RESULTSEleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14% (95%CI: 2%-25%, P = 0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16% (95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12% (95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14% (95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics (95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo (8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo (OR = 1, 95%CI: 0.06-18.08).CONCLUSIONProbiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.

Efficacy of Rifaximin to Eradicate Small Intestine Bacterial Overgrowth and to Get Symptom Relief: A Systematic Review and Meta-Analysis

Introduction: Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterized by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based. The aim of this study was to perform a systematic review and meta-analysis to summarize evidence about the efficacy of rifaximin to eradicate SIBO and to get symptoms relief. Methods: MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for randomized controlled trials (RCTs) and observational studies. Furthermore, abstract books of major European, American, and Asian gastroenterological meetings were also examined. To explore heterogeneity regarding the efficacy and the safety, a meta-regression analysis including several variables were performed. Studies reporting lower GI symptom assessment before and after treatment with rifaximin were evaluated in order to identify those showing symptoms relief after therapy from those which did not. A sub-group analysis was also performed to evaluate the eradication rate in patients with irritable bowel syndrome (IBS). Results: 32 studies involving 1331 patients were included. The overall eradication rate according to intention to treat analysis was 70.8% (95% CI: 61.4 to 78.2; I2 = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5 to 79.8; I2 = 87.5%). Meta-regression identified three covariates (namely the drug dose, the study design and co-therapy) independently associated with an increased eradication rate. In IBS patients, the pooled eradication rate according to the ITT analysis was 71.6% (95% CI: 56.7 to 84.4) and according to PP analysis was 75.4% (95% CI: 65.0 to 84.5). The evaluation of studies assessing symptoms before and after treatment with rifaximin showed a high heterogeneity, not allowing a proper meta-analysis. However, a thorough analysis of the studies showed that symptom improvement was reported in a large proportion (≥75%) of studies, an effect seen more frequently in studies including IBS patients. The overall rate of adverse events was 4.6% (95% CI = 2.3 to 7.5; I2 = 63.6%). Conclusion: Rifaximin treatment seems to be effective and safe to eradicate SIBO and to get symptoms relief, even in patients with IBS. However, the quality of the available studies is generally poor. Well-designed RCTs are needed to substantiate these findings and to establish the optimal regimen.

Review: A Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: Is superiority an illusion?

Vonoprazan (VPZ) is a novel acid suppressant that has been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of VPZ vs proton-pump inhibitor (PPI) in H. pylori eradication therapies remain controversial. To perform a meta-analysis in order to assess the efficacy and safety of VPZ vs PPI for H. pylori eradication. The PubMed, EMBASE, and Cochrane Library databases were searched up to July 10, 2017, for relevant randomized controlled trials (RCTs) and nonrandomized clinical studies (NRCTs). The pooled eradication rate (ER) and pooled occurrence rates of adverse events were used to compare the efficacy and safety of VPZ - and PPI-containing regimens. A total of 14 studies with 14636 patients were included in this meta-analysis. The results showed that the pooled ER of VPZ -containing regimens was much higher than that of PPI-containing regimens when used as first-line therapies. This difference was significant for both intention-to-treat (85.1% vs 68.0%, P<.00001) and per-protocol analyses (89.0% vs 74.2%, P<.00001). Moreover, subgroup analysis indicated significant superiority of VPZ in both patients with clarithromycin-resistant strains (81.5% vs 40.9%, P<.00001) and those with clarithromycin-susceptible strains (94.9% vs 89.6%, P=.006). However, VPZ did not show superiority to PPI as part of a second-line triple therapy based on both intention-to-treat (83.4% vs 82.0%, P=.79) and per-protocol analyses (89.3% vs 90.1%, P=.06). Finally, RCT subgroup analysis showed the safety of VPZ -containing regimens to be better than PPI-containing regimens (26.4% vs 33.3%, P=.008), whereas there was no significant difference in this regard for the NRCT subgroup analysis (5.7% vs 4.7%, P=.08). The efficacy of VPZ is superior to PPI in first-line H. pylori triple eradication therapies but not in second-line therapies. The safety of VPZ -containing regimens appears to be equal or even superior to that of PPI. However, most reports included in this study had low levels of evidence. Hence, adequate and high-quality RCTs will be needed to support our results.