Empiric “Three-in-One” Bismuth Quadruple Therapy for Second-Line Helicobacter pylori Eradication: An Intervention Study in Southern Italy

The eradication of Helicobacter pylori (H. pylori) may be difficult due to antibiotic resistance. Indeed, after one failure, a second-line therapy is needed and a bismuth containing quadruple therapy (BQT) with a three-in-one capsule formulation is becoming very popular. Therefore, we aimed to evaluate effectiveness and safety of BQT as a second-line therapy. We recruited consecutive patients with one therapy failure. For ten days patients received the three-in-one BQT Pylera® therapy, in combination with a proton-pump inhibitor (PPI), decided at the choice of the investigator, at full dose bid. The eradication rate was calculated by intention-to-treat (ITT) and per-protocol (PP)analyses and 95% confidence intervals (CI) were calculated. Seventy-three patients were recruited, 41 females and 32 males (mean age 53.0±13.1 years). Fifty-five patients failed triple therapy with amoxicillin and clarithromycin and the remaining 18 received sequential therapy. Seventy-two patients consumed at least 90% of the capsules, while only one did not complete the therapy due to adverse events (nausea and diarrhea). By ITT analysis, BQT was successful in 62 subjects (eradication rate 84.9%, 95%CI 76.7–93.1%). By PP analysis, the eradication rate was 86.1% (95%CI 78.1–94.1%).Adverse events were observed in 14 subjects (20.5%).In conclusion, our report confirmed that BQT is effective as an empiric second-line regimen.

Efficacy of Twice a Day Bismuth Quadruple Therapy for Second-Line Treatment of Helicobacter pylori Infection

Bismuth quadruple therapy (BQT) is an effective treatment for Helicobacter pylori infection. However, frequent dosing schedules of BQT regimen often compromise drug adherence and may affect treatment outcomes. This retrospective study aimed to investigate the efficacy of twice-daily BQT compared to that of four times a day therapy. From August 2018 to November 2020, adult patients who failed first-line standard triple therapy and underwent BQT were eligible. Patients were categorized into two groups according to dosing schedule: (i) the BQT group (n = 213) who received standard BQT administered four times a day; and (ii) the BQTb group (n = 141) who received proton pump inhibitor, bismuth 600 mg, metronidazole 500 mg, and tetracycline 1 g twice a day. The eradication rate did not differ between the BQT (92.5%) and the BQTb groups (90.1%) (p = 0.441). Adherence and adverse event rate were similar between the two groups. Multivariate analysis showed that current smoking was associated with eradication failure; however, dosing frequency was not associated with the efficacy of eradication therapy. This study suggested that twice a day BQT is as effective as four times a day therapy for second-line treatment of H. pylori infection.

Fourteen-Day Sequential Therapy Containing Rabeprazole Versus 10 And 14-Day Concomitant Therapy in The First Line Treatment of Helicobacter Pylori Infection: A Randomized, Open-Label Clinical Trial

Aims:To compare an optimized sequential therapy to 10 and 14-day non-Bismuth quadruple therapies currently recommended, in terms of efficacy, incidence of adverse effects and cost.Patients and methods:This open-label prospective study randomized patients with confirmed Helicobacter pylori (H.Pylori) infection to 3 groups (1:1:1): The first group received quadruple therapy of twice-daily (bid) Omeprazole 20mg, Amoxicillin 1g, Clarithromycin 500mg and Metronidazole 500mg for 10days (QT-10), the second group received a 14 day quadruple therapy following the same regimen (QT-14), and the third received an optimized sequential therapy consisting on a bid Rabeprazole 20 mg plus amoxicillin 1g for 7 days, followed by bid Rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500mg for the next 7 days (OST-14). Adverse events (AEs) were recorded throughout the study, and the H.Pylori eradication rate was determined 4 to 6 weeks after treatment using the 13C urea breath test.Results:In intention to treat analysis, eradication rate was 85,5%, 91,8% and 95,4% respectively in QT-10, QT-14 and OST-14 groups (p=0,03). In the per protocol analysis, the eradication rate was significantly higher in the OST- 14 group compared to the QT-14 and QT-10 groups (98,1%, 94,4% and 89,5% respectively, p=0,02).The overall incidence of AEs was significantly lower in the OST-14 group (p=0,01). Furthermore, the OST-14 was the most cost-effective among the three groups.Conclusion:14-day optimized sequential therapy is a safe and effective alternative that allows a higher eradication rate compared to 10 and 14-days quadruple therapies while causing less adverse effects and allowing a gain in term of cost.

Saccharomyces boulardii Combined With Quadruple Therapy for Helicobacter pylori Eradication Decreased the Duration and Severity of Diarrhea: A Multi-Center Prospective Randomized Controlled Trial

Background: Whether probiotics helped the Helicobacter pylori (H. pylori) eradication was still highly controversial. The non-bacterial Saccharomyces boulardii (S. boulardii) has demonstrated its efficacy in the treatment of antibiotic-associated and infectious diarrhea. We aimed to evaluate the effects of S. boulardii combined with quadruple therapy for H. pylori eradication and associated side effects.Methods: Three hundred and sixty H. pylori-infected patients were recruited in this multicenter, randomized controlled trial. The patients who underwent H. pylori eradication treatment were randomized in a ratio of 1:1 into two separate groups that received standard quadruple therapy (Group A) and quadruple therapy plus S. boulardii sachets (Group B) for 14 days. The everyday medication and side-effect records were collected for compliance and adverse effect analysis. All patients accepted 13C/14C-urea breath tests 4 weeks after the therapy completion.Results:Saccharomyces boulardii and quadruple therapy-combined intervention significantly reduced the incidences of overall side effects (27.8 vs. 38.5%, p = 0.034) and diarrhea (11.2 vs. 21.2%, p = 0.012) in Group B compared with quadruple therapy alone in Group A, especially reduced the diarrhea duration (5.0 days vs. 7.7 days, p = 0.032) and incidence of severe diarrhea (4.7 vs. 10.1%, p = 0.040). Intention-to-treat (ITT) analysis and per-protocol (PP) analysis both indicated no statistical differences of eradication rate between Groups A and B (ITT: 82.7 vs. 85.8%, p = 0.426; PP: 89.7 vs. 94.2%, p = 0.146). The joint use of S. boulardii and quadruple therapy markedly improved the overall pre-eradication alimentary symptoms (hazard ratio (HR): 2.507, 95% CI: 1.449–4.338) recovery.Conclusion:Saccharomyces boulardii ameliorated H. pylori eradication-induced antibiotic-associated side effects especially reduced the incidence of severe diarrhea and the duration of diarrhea. However, there was no significant effect of S. boulardii on the rate of H. pylori eradication.Trial Registration: The protocol had retrospectively registered at ClinicalTrails.gov, Unique identifier: NCT03688828, date of registration: September 27, 2018; https://clinicaltrials.gov/show/NCT03688828

Investigating the Effect of Quadruple Therapy with Saccharomyces Boulardii or Lactobacillus Reuteri Strain (DSMZ 17648) Supplements on Eradication of Helicobacter Pylori and Treatments҆ Side Effects: A Double-Blind Placebo-Controlled Randomized Clinical Trial

Background: The primary goal of this placebo-controlled study was to determine the effect of quadruple treatment with Saccharomyces boulardii or Lactobacillus reuteri on the eradication of Helicobacter pylori and side effects of the treatment.Results: This study was a double-blind, randomized, placebo-controlled trial. And, eradication of helicobacter pylori was reported comparing conventional anti-H. Pylori therapy versus conventional therapy supplemented with S. boulardii and L. reuteri DSMZ 17648. For this aim, a total of 156 patients were included in the current study; and patients positive for H. Pylori infection (n =156) were randomly assigned to 3 groups: 52 patients (Group P) received conventional quadruple therapy plus L. reuteri, 52 patients (Group S) received conventional quadruple therapy plus S. boulardii daily, for 2 weeks, and 52 patients were in the control group (Group C). At the end of the treatment period, all the subjects continued to take proton pump inhibitor (PPI) alone for 14 days, and then, no medication was given for 2 weeks again. During follow-up, gastrointestinal symptoms were assessed using an evaluation scale (Glasgow dyspepsia questionnaire (GDQ)), and adverse events were assessed at 7, 14, 21, and 28 days. As a result, eradication therapy was effective for 94.2% of subjects in Group S, 92.3% of subjects in Group P, and 86.5% of subjects in the control group, with no differences between treatment arms. In Group S, the chance of developing symptoms of nausea (OR=2.74), diarrhea (OR=3.01), headache (OR=10.51), abdominal pain (OR=3.21), and anxiety (OR=3.58) was significantly lower than in the control group (p<0.05).Conclusion: In general, our findings revealed that the use of probiotic supplements containing S. boulardii or Lactobacillus reuteri (DSMZ 17648 strain) improved the eradication rate of H. Pylori infection, but it was not statistically significant. Therefore, it is recommended to conduct future research with a larger sample size to investigate the effect of S. boulardii supplementation on eradicating H. pylori infection and reducing treatment side effects.Trial registration: IRCT20200106046021N1, this trial was registered on Jan 14, 2020.

Olanzapine (5 mg) Plus Standard Triple Antiemetic Therapy for the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting: A Prospective Randomized Controlled Study

Objective A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. Methods Patients received 3-day cisplatin-based chemotherapy(25mg/m2/d) were given either 5mg olanzapine quadruple therapy (aprepitant, tropisetron, dexamethasone) or 5mg olanzapine-based triplet therapy. The primary end-point was the complete response(CR) in the overall phase(OP)(0-120h) between quadruple regimen group and triplet regimen group. The secondary end-points were the CR in the acute phase(AP)(0-24h), delayed phase(DP)(25-120h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy induced nausea and vomiting(CINV) on the quality of life was assessed by the Functional Living Index-Emesis(FLIE). Aprepitant-related adverse effects (AEs) was also recorded. Results (1) The primary end-point CR during overall phase was 76.0% (45/59) vs 67.0% (41/61) between the quadruple regimen group and triplet regimen group(P =0.271). The secondary end-point CR during the AP was significantly higher in the quadruple group than in the triple group, which was 100.0%(59/59) vs 93.0%(57/61)(P=0.045). The difference between the groups was especially greater in the delayed phase(quadruple group 76.0% (45/59) vs triple group 67.0%(41/61)(P=0.271)). The rate of patients who achieved total protection in the overall phase was also larger in the quadruple group than in the triple group(28.8% (17/59) vs 23.0%(14/61)(P=0.463)). During the OP, the incidence of no vomiting in quadruple group and triple group was 93.2%(55/59) vs 80.3%(49/61)(P=0.038)respectively.(2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group than in the triple group(P=0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire >108, this study exhibited identical life quality in quadruple group and the triplet group.(3) The most common aprepitant- and olanzapine-related AEs included sedation, fatigue and constipation. The occurrences between two groups were identical. Conclusion It may been recommended that combined 5mg olanzapine with aprepitant, tropisetron, dexamethasone quadruple therapy for the prevention of multiple-day cisplatin induced nausea and vomiting due to the better CINV control rate and safety.