Quadruple Regimen Research Articles

Effects of Helicobacter pylori and Helicobacter pylori eradication on the microbiota of tongue coating

Eradicating Helicobacter pylori (H. pylori) can cause an imbalance in the microbiota. Dysbiosis of the gut microbiome may produce multiple diseases and bacterial infections. The objective of this study was to investigate the influence of Helicobacter pylori (H. pylori) infection and its eradication on the composition of the oral tongue coating microbiota. A cohort of 35 participants was recruited and categorized into two groups: the H. pylori negative group (N group) consisting of 12 individuals and the H. pylori positive group (23 individuals). Within the H. pylori positive group, subjects were further stratified into the H. pylori pre-eradicated group (HPQ group) and the H. pylori eradicated group (HPH group). H. pylori positive individuals were treated with a quadruple regimen containing bismuth, and tongue coating samples were collected both prior to and following treatment. Concurrently, tongue coating samples were collected from H. pylori negative individuals. High-throughput 16S rRNA sequencing technology was employed to assess the microbial composition of the tongue coating in the N group, HPQ group, and HPH group. Pertinent clinical data were documented.Microbial diversity was found to significantly differ among the N group, HPQ group, and HPH group, as evidenced by variations in Chao1 index, Shannon index, and Partial Least Squares Discriminant Analysis (PLS-DA). The dominant bacterial phyla identified across all groups included Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, Actinobacteria, and Saccharibacteria. At the phylum level, Firmicutes exhibited higher relative abundance in the HPQ group in comparison to both the N group and HPH group. Conversely, Bacteroidetes displayed greater prevalence in the N group and HPH group. Linear Discriminant Analysis Effect Size (LEfSe) analysis indicated a higher abundance of Romboutsia, Rothia, and Turiciactor in the HPQ group. Our study revealed significant disparities in microbial diversity and richness among the three groups. Furthermore, our findings suggest a potential association between the presence of Streptococcus, Rothia and H. pylori positive individuals.

Insights from Clinical Trials: Evidence-Based Recommendations for Induction Treatment of Newly Diagnosed Transplant-Eligible Multiple Myeloma.

Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. This analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2023, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, objective response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care.

Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker-Based Dual, Triple, and Quadruple Regimens for First-Line Helicobacter pylori Infection Treatment: A Systematic Review and Network Meta-Analysis.

In the last few years, numerous new potassium-competitive acid blocker (P-CAB)-based randomized controlled trials (RCTs) concerning the first-line regimens for Helicobacter pylori infection treatment from various countries have been published. However, no network meta-analysis (NWM) exists, which examines the comparative efficacy and safety of P-CAB-based dual, triple, and quadruple treatments, and, therefore, in this NWM, we examined this matter comparing efficacy and safety of these P-CAB-based regimens. Databases were searched for identification, screening, eligibility, and inclusion of relevant RCTs. Extracted data were entered into a Bayesian NWM, and the ranking order for each regimen was evaluated by means of the surface under the cumulative ranking area values. Twenty-five eligible RCTs were included with 7,605 patients randomized to 6 first-line regimens, i.e. P-CAB dual therapy, P-CAB triple therapy, P-CAB quadruple therapy, PPI dual therapy, PPI triple therapy, and PPI quadruple therapy. The surface under the cumulative ranking area values (%) for these 6 regimens were 92.7, 62.5, 33.9, 75.1, 19.4, and 16.3, respectively. The comparative effectiveness ranking showed that P-CAB dual therapy regimen ranked first for efficacy and last for adverse effects and had the best profile for integrated efficacy-safety. In this NWM concerning the comparative efficacy and safety of P-CAB-based dual, triple, and quadruple regimens for the first-line H. pylori infection treatment, the overall results showed that P-CAB-based dual treatment ranked first for efficacy with the best-integrated efficacy-safety profile. This is of importance, since the dual regimens overcome the crucial issue of clarithromycin resistance. Consequently, these findings are expected to be useful in helping clinical decision making and future guidelines.

Long-term outcomes in rapamycin on renal allograft function: a 30-year follow-up from a single-center experience

ObjectivesTo evaluate long-term renal graft prognosis and the role of rapamycin from a single-center in China over a 30-year follow-up.MethodsThis study enrolled a total of 654 patients who underwent kidney transplantation between 1989 and 2020. The basic characteristics of the included patients were collected. Graft survival was described and compared using Kaplan-Meier curves (K-M curves). Both continuous and categorical variables were included in a multivariate Cox proportional-hazards model. Patients were divided into rapamycin-based quadruple immunosuppression regimen group (rapa group, n = 41) and conventional tacrolimus-based triple immunosuppression regimen group (control group, n = 218). The indication biopsy results of the two groups were further reviewed to compare the incidence of rejection, acute rejection, and banff score.ResultsThe overall 5, 10, 15, 20-year graft survival rate of our center is 87.5%, 62.4%, 46.4% and 20.9%, respectively. The median survival time after surgery is 14 years. Multiple Cox regression analysis identified BMI (p = 0.035), dialysis type (p < 0.001), immunosuppressants (p < 0.01), urine albumen (p < 0.001), globulin (p = 0.041), and blood glucose (p = 0.002) as risk factors. The 20-year, 10-year and 5-year AUC is 0.78, 0.75 and 0.75. The combination of FK506 and rapamycin was further suggested by the model to effectively improve the graft prognosis (p < 0.01, HR = 0.763). The K-M curve showed that the long-term survival rate of renal grafts in the rapa group was significantly better than that in the conventional group (p < 0.001). In addition, indication biopsy records revealed a lower possibility of immune rejection in the rapa group than that in the conventional group (p < 0.001). Banff score indicated that rapa group had less vascular inflammation in the transplanted kidney.ConclusionsIn this study, a 30-year follow-up was performed in a single center, and a total graft 20-year survival rate of 20.9% was reported. The prognostic model and subgroup analysis suggested that FK506 combined with rapamycin could effectively improve the prognosis of renal transplantation, which could be explained by reduced acute rejection and less vascular inflammation.

Study on the clinical efficacy of 14-day vonoprazan-based triple regimen in obese patients with Helicobacter pylori infection

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the 13C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

Who Can Receive Clinical Benefit from Mid-Term Vericiguat Add-on Therapy Among Patients with Systolic Heart Failure Receiving Quadruple Medical Therapy?

Vericiguat, a soluble guanylate cyclase stimulator known for augmenting cyclic guanosine monophosphate production, has garnered substantial clinical attention in patients with systolic heart failure. Despite its proven efficacy, discerning the specific subset of individuals who can enjoy clinical advantages from vericiguat therapy in contemporary real-world clinical practice, particularly among the individuals undergoing "quadruple medical therapy" comprising administration of a beta-blocker, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitor, remains an unresolved query. This study involved patients undergoing 3-month vericiguat therapy alongside complete quadruple medical therapy in a contemporary real-world clinical practice. Baseline characteristics associated with the primary outcome, defined as a reduction in serum NT pro-B-type natriuretic peptide (BNP) levels over the 3-month therapeutic duration, were scrutinized. A cohort of 24 patients (median age: 66 years; 20 males) were included. All participants diligently adhered to the 3-month vericiguat therapy in conjunction with the quadruple medical regimen. A higher baseline systolic blood pressure emerged as an independent factor linked to the primary outcome, yielding an adjusted odds ratio of 1.31 (95% confidence interval: 1.03-1.65, P = 0.026) at a threshold of 105 mmHg. This threshold notably stratified the trajectories of serum NT pro-BNP levels during the 3-month vericiguat therapy. In conclusion, preservation of baseline systolic blood pressure emerged as a pivotal determinant for reaping the clinical benefits from mid-term vericiguat therapy among patients with systolic heart failure receiving quadruple medical therapy.

Antiemetic prophylaxis regimens in haematologic malignancies patients undergoing a hematopoietic stem cell transplantation. Which is the best standard of care? A systematic review.

This systematic review, adhering to PRISMA guidelines, aimed to evaluate the efficacy and safety of antiemetic prophylaxis in haematological patients undergoing high-dose chemotherapy as part of their hematopoietic stem cell transplantation (HSCT) conditioning regimens. We performed a comprehensive search in PubMed, EMBASE, ClinicalTrials.gov and the Cochrane database to identify randomised controlled trials (RCTs) and systematic reviews of antiemetic prophylaxis. Studies in English, French, Italian or Spanish were included. This review is registered with PROSPERO, ID CRD42023406380. Eight RCTs were analysed. The antiemetic regimens evaluated ranged from monotherapy with 5-Hydroxytryptamine Receptor 3 antagonists (5-HT3RAs) to complex combinations including olanzapine, neurokinin-1 receptor antagonists, 5-HT3RAs and corticosteroids. Complete response rates for triplet or quadruple regimens varied between 23.5% and 81.9%. Although no significant adverse effects were observed, minor symptoms such as diarrhoea, constipation, sedation and headaches were reported. Existing evidence on HSCT antiemetic therapy highlights its benefits but fails to provide clear clinical directions. The choice between triplet and quadruplet therapies for different patient scenarios is still uncertain. Until more detailed research is available, healthcare providers must rely on the latest guidelines and their judgement to customise antiemetic care for each patient's specific needs and risks.

Real-World Situation of Eradication Regimens and Risk Factors for Helicobacter pylori Treatment in China: A Retrospective Single-Center Study.

The success rate of Helicobacter pylori (H. pylori) eradication in China is declining. The aim of this study was to evaluate eradication outcomes in clinical practice and identifies factors contributing to treatment failure. A retrospective review was conducted on patients treated for H. pylori infection with 14-day bismuth-containing quadruple therapy at a Beijing medical center from January 2020 to December 2023. We analyzed demographic and clinical data, eradication rates across regimens, and performed multivariate analysis to pinpoint predictors of failure. Out of 3340 participants, 2273 (68.1%) achieved eradication. Amoxicillin-based combinations (69.2%) outperformed other antibiotic regimens (58.9%, p < 0.001), with amoxicillin plus doxycycline reaching a 71.4% success rate. Esomeprazole-based regimens were more effective (73.6%) than other PPI regimens (65.2%, p = 0.001), notably, a rabeprazole, amoxicillin, doxycycline, and bismuth combination had an 80.0% success rate. Age, gender, and smoking and drinking were significant eradication failure predictors. In real-world settings, 14-day amoxicillin and esomeprazole-based quadruple regimens have been demonstrated to be more effective than other regimens. Age, gender, and lifestyle habits are identified as independent risk factors for eradication failure. This study was registered in the Chinese Clinical Trial Registry on 08/01/2024 (clinical trial registration number: ChiCTR2400079647).

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20mg twice daily; bismuth 220mg twice daily; amoxicillin 1000mg twice daily; and either clarithromycin 500mg twice daily or tetracycline 500mg four times daily. At least 6weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Abstract PO3-27-12: Dexamethasone is necessary for preventing acute emesis induced by anthracycline/cyclophosphamide chemotherapy (HELEN-009) : a multicenter, randomized, open-labeled phase 3 trial

Abstract Background Olanzapine, in combination with NK1 receptor antagonist (RA), 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone, is now the standard approach to prevent chemotherapy-induced nausea and vomiting (CINV). In this study, we assessed the preventive effect of removing dexamethasone from the quadruple standard antiemetic regimen on CINV caused by anthracycline/cyclophosphamide chemotherapy. Methods The HELEN-009 was a multicenter, randomized, open-labeled phase 3 trial to evaluate the efficacy of NK1RA,5-HT3RA and Olanzapine triplet-combination antiemetic therapy done in 3 hospitals in China.Key inclusion criteria were patients with early breast cancer who were scheduled to be treated with epirubicin plus cyclophosphamide chemotherapy for the first time, age between 18 and 75 years, and with Eastern Cooperative Oncology Group performance status of 0–1. Eligible patients were randomly assigned (1:1) to receive either fosaprepitant, tropisetron, dexamethasone and olanzapine(quadruple group)or fosaprepitant, tropisetron and olanzapine without dexamethasone(triple group). Patients were randomly assigned to interventions by use of a web entry system and the minimization method with a random component, with age as factors of allocation adjustment. The primary endpoint was the proportion of patients who achieved a complete response, defined as absence of vomiting and no use of rescue medications in the overall phase (days 1–5) after starting chemotherapy. All randomly assigned patients who satisfied eligibility criteria received epirubicin plus cyclophosphamide chemotherapy were included in efficacy analysis. All patients who received any treatment in this study were assessed for safety. This study is registered at Clinical Trials Registry, number NCT05242874. Findings Between January 2022 and July 2023, 439 patients with breast cancer were enrolled in the study, with 218 participants randomly assigned to quadruple group and 221 participants assigned to triple group. All eligible patients were observed 120 h after epirubicin plus cyclophosphamide chemotherapy initiation. One patient in the quadruple group withdrew consent. One patient in the quadruple group and one in triple group discontinued treatment on day 1 and was excluded from the efficacy analysis. In the overall phase, the proportion of patients who achieved a complete response was 180 (83.3% [95% CI 78.3–88.3] of 216 patients in the quadruple group and 137 (62.4% [55.8–68.7] of 220 patients in the triple group (p&amp;lt; 0·0001). No grade 3 or higher treatment-related adverse events occurred in either of the groups. Interpretation Dexamethasone remains essential in preventing acute emesis in patients receiving epirubicin plus cyclophosphamide chemotherapy. Table. Proportion of patients in the efficacy analysis set achieving a complete response Table. Treatment-related adverse events with an incidence ≥ 2% Citation Format: Xiuchun Chen, Jiao Dechuang, Chongjian Zhang, Xianfu Sun, Zhenduo Lu, Lianfang Li, Jianghua Qiao, Chengzheng Wang, Min Yan, Yueqing Feng, Ya Wei, Zhenzhen Liu. Dexamethasone is necessary for preventing acute emesis induced by anthracycline/cyclophosphamide chemotherapy (HELEN-009) : a multicenter, randomized, open-labeled phase 3 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-12.

Efficacy and safety of bismuth quadruple regimens containing minocycline and vonoprazan for eradication of Helicobacter pylori: Real-world evidence.

To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.

Fourteen-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication in an area with high clarithromycin and levofloxacin resistance: a prospective randomized study (VQ-HP trial)

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3–94.2 and 94%, 95% CI 87.4–100, respectively (RR difference 0.25, 95% CI 0.03–0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.

Vonoprazan is Not Inferior to Proton Pump Inhibitors in Bismuth-containing Quadruple Therapy for Helicobacter pylori Eradication: A Meta-analysis of 10 Studies From East Asia.

To investigate the efficacy and safety of vonoprazan based bismuth-containing quadruple therapy (VBCQ) in eradicating Helicobacter pylori (Hp). The VBCQ and the proton pump inhibitor-based bismuth-containing quadruple regimen (PBCQ) were compared by retrieving relevant studies in Pubmed, Embase, Cochrane Library, CNKI, and Wanfang data. Combined analysis was performed with risk ratio (RR) and 95% CI as effect values. A total of 10 studies were enrolled, including 7 randomized controlled trials and 3 cohort studies. In intention-to-treat analysis, the eradication rate of VBCQ (89.24%, 1103/1236) was significantly higher than that of PBCQ (84.03%, 1021/1215), with RR = 1.06 (95% CI: 1.03~1.10). In per-protocol analysis, the eradication rates of VBCQ and PBCQ were 92.94% (895/963) and 87.82% (829/944), respectively, with a significant difference (RR = 1.06, 95% CI: 1.03~1.09). Subgroup analysis of study design types shared similar results. VBCQ and PBCQ showed an incidence of adverse reactions of 37.30% (304/815) and 34.94% (282/807), respectively. Significant differences were not found between the two groups (RR = 1.07, 95% CI: 0.96-1.19), nor in subgroup analysis. The good compliance rates in VBCQ and PBCQ groups were 94.32% (216/229) and 95.13% (215/226), respectively, with no significant difference (RR = 0.99, 95% CI: 0.95~1.04). VBCQ has a higher eradication rate on Hp than PBCQ, while its adverse reactions and compliance are similar to PBCQ. However, we conservatively believe that in Hp eradication, the VBCQ is not inferior to PBCQ because of the small absolute difference.

Helicobacter pylori infection diagnosis and management: current practices of Greek gastroenterologists.

The diagnosis and management of Helicobacter pylori (H. pylori) infection vary significantly, depending on country, area, and specialty. The aim of this study was to record the current practices of Greek gastroenterologists in the screening and treatment of H. pylori infection. An anonymous questionnaire consisting of 19 questions about the management of H. pylori infection was sent with the aid of the Hellenic Society of Gastroenterology to all members of the Society. The questionnaire was completed by 180 gastroenterologists, with a response rate of 31.4%. Diagnostic tests to confirm H. pylori infection are ordered by >90% of the gastroenterologists for patients with current peptic ulcer disease, gastric lymphoma, family history of gastric cancer, and an endoscopic appearance suggestive of gastritis. Most gastroenterologists (55.8%) also tested for H. pylori in patients with gastroesophageal reflux disease (GERD). Histopathology was the most preferred (60.6%) method when testing was decided during endoscopy, while urea breath test was the most preferred method (67.8%) regardless of endoscopy. Most gastroenterologists use quadruple eradication regimens supported by international guidelines (90%), while 65.6% of the physicians answered that they systematically recommend the addition of probiotics to standard therapy. Most physicians (82.8%) answered that they always confirm the eradication of the pathogen. The majority of Greek gastroenterologists conform to the recommendations of international guidelines regarding the diagnosis and management of H. pylori infection, except for the screening of patients with GERD. A considerable number of doctors use probiotics in addition to standard therapy.

Sequential therapy versus quadruple therapy for Helicobacter pylori eradication: A prospective double-blinded randomized controlled trial.

This controlled randomized clinical trial was designed to compare effectiveness, side effects, and severity of symptoms before and after therapy between quadruple (QT) and sequential regimens (SQ) for Helicobacter Pylori (H. pylori). Patients were randomly allocated into two groups. Group A received a 14-day QT including pantoprazole 40 mg q12 h, bismuth subcitrate 240 mg q12 h, clarithromycin 500 mg q12 h, and amoxicillin 1000 mg q12 h and group B received ST including pantoprazole 40 mg q12 h and amoxicillin 1000 mg q12 h for the initial 5 days followed by pantoprazole 40 mg q12 h, clarithromycin 500 mg q12 h and tinidazole 500 mg q12 h for the next 5 days. Adverse drug reactions and patients' compliance were assessed after finishing the treatment course and also 4 weeks after. All patients were naive, therefore ST and QT were first-line therapies. To evaluate severity of symptoms we used Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) before taking the first dose of regimens, at the end of therapy, and also 4 weeks after (follow-up). The mean age in Group A (n = 83) was 48.55 ± 12.56 and 47.24 ± 12.78 in Group B (n = 79). No statistically significant differences were observed between the two groups regarding age, gender, endoscopic findings, and also eradication rate. The analysis demonstrated a significant decrease in SF-LDQ score between baseline and after therapy and baseline and follow-up in both regimen groups. Both regimens were well tolerated by the majority of patients, and there were no significant differences between the two groups in terms of adverse drug reactions. This study showed that ST can be used as an alternative first-line therapy to QT in patients with H. pylori infection.

National survey questionnaire on the diagnosis and treatment status of Helicobacter pylori in peptic ulcer bleeding disease.

The Maastricht VI/Florence Consensus and Chinese National Consensus Report provide comprehensive guidelines for treating Helicobacter pylori infection. This study aimed to assess physicians' understanding of and adherence to this consensus in different hospitals. Chinese medical staff attending gastrointestinal conferences across various regions were selected for this study. The questionnaire included: 1. the number of patients with peptic ulcer bleeding in hospitals of different levels annually and the diagnostic methods used for H. pylori; 2. whether routine H. pylori examination was conducted and the specific methods employed; and 3. Treatment plans for H. pylori eradication; 4. The mean follow-up duration after treatment 5. Plans for re-eradication in cases of H. pylori treatment failure. Across all levels of Chinese hospitals, the urea breath test was the most commonly used method for detecting H. pylori infection. Most primary (81.53%), secondary (89.49%), and tertiary (91.42%) centers opted for a 14-day quadruple regimen. The preferred antibiotic regimen at all hospital levels was amoxicillin+clarithromycin, with rates of 63.69, 58.08, and 59.27% in the primary, secondary, and tertiary hospitals, respectively. The rates of H. pylori re-examination were 68.15, 87.07, and 87.46% in the primary, secondary, and tertiary hospitals. If H. pylori eradication failed, hospitals at different levels choose to replace the initial plan. There is a need for an enhanced understanding of and adherence to guidelines for H. pylori among physicians in hospitals at all levels.

Efficacy assessment of diverse antibiotic combinations in bismuth quadruple regimens and risk factors for Helicobacter pylori eradication: a retrospective single-center study in China

Efficacy assessment of diverse antibiotic combinations in bismuth quadruple regimens and risk factors for Helicobacter pylori eradication: a retrospective single-center study in China

Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial

BackgroundOwing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance.MethodsThis randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses.DiscussionThis study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration.Trial registrationKorean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do.

Independent Risk Factors Predicting Eradication Failure of Hybrid Therapy for the First-Line Treatment of Helicobacter pylori Infection.

Hybrid therapy is a recommended first-line anti-H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori-infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.

A Phase II Multicenter Clinical Trial Assessing the Safety and Efficacy of Ixazomib, Pomalidomide and Dexamethasone Combination As Second or Third-Line Treatment for Triple-Class Exposed Patients with Relapsed and Refractory Multiple Myeloma (iPod-790 Trial)

Introduction: Despite significant improvement in the outcomes of early treatment lines in myeloma, most patients (Pts) invariably relapse. As triple and quadruple regimens are being introduced at the upfront setting, many Pts are either triple-class exposed or triple-class refractory (TCE/TCR) early in their disease course. Although novel immunotherapies are emerging with impressive efficacy among TCE/TCR myeloma Pts, their use is currently limited due to potential toxicities, costs and logistic constraints. We report the outcomes of the IPoD-790 clinical trial (NCT04790474), an all-oral regimen: ixazomib (IXA), pomalidomide (POM) and dexamethasone (DEX) (IPd) combination, in Pts with relapsed refractory multiple myeloma (RRMM) who progressed after bortezomib (BTZ), lenalidomide (LEN) and daratumumab (DARA) therapies. Methods: A phase 2, investigator initiated, open-label, single-arm, prospective, multicenter study evaluating the safety, tolerability and efficacy of IPd as a second or third-line combination treatment for TCE RRMM Pts. Pts receive IXA: 3 mg days (d) 1,4,8,11 of 21-d Cycles (Cy) 1-3; 4mg d 1,8,15 of 28-d Cy 4-24. POM 4mg: d 1-14 Cy 1-3; d 1-21 Cy 4-24. DEX 20mg: d 1,2,8,9,15,16 Cy 1-3; d 1,2,8,9,15,16,22,23 Cy 4-24. Treatment continues for 24 cycles, or until disease progression (PD) or unacceptable toxicity (the earliest of the three). After completion of 24 treatment cycles, Pts continue POM DEX as standard of care. The primary endpoint is progression free survival (PFS) according to IMWG criteria. Results: Fifty-five (out of the 60 Pts planned) were enrolled; we report data on 46 Pts who had their first dose between March 2021 and April 2023, further data will be presented at the meeting. The median age was 72 (range: 53-88); 18 (39%) were ≥75 years old; 59% were male, ISS was I/II/II for 48% / 25% and 28% respectively; 59% had high risk FISH cytogenetics (t(4:14), t(14:16), +1q21, del17p) with 14% double-hit. Nine percent had extramedullary disease at study enrollment. Exposure rates to BTZ, LEN and DARA were 100%, 98% and 96%, respectively. Forty-one percent had undergone autologous bone marrow transplantation. Refractoriness rates to BTZ, LEN and DARA were 57%, 91% and 65%, respectively. Thirty-seven percent were TCR. At data cutoff date of 15-Jun-2023, the median follow-up time was 10.4 [95% CI 7.6-13.2] months. Ninety-three percent of the Pts had at least one treatment emergent adverse event (TEAE) and 65% had a TEAE grade 3 or 4. Common (≥ 10%) TEAEs include neutropenia 35% (28% Gr 3 or 4), pneumonia 24% (17% Gr 3 or 4), thrombocytopenia 22% (15% Gr 3 or 4), back pain 22% (2% Gr 3 or 4), asthenia 20% (0% Gr 3 or 4), diarrhea 20% (0% Gr 3 or 4), peripheral edema 20% (2% Gr 3 or 4), COVID19 infection 15% (2% Gr 3 or 4 ), anemia 13% (2% Gr 3 or 4), acute kidney injury (AKI) 13% (7% Gr 3 or 4), rash 13% (0% Gr 3 or 4). At data cut-off date, 31 Pts (67%) discontinued the study treatment; 20 (43%) due to PD, 7 (15%) due to adverse events (including 3 patients with pneumonia, and 1 patient each with COVID19 infection, campylobacter gastroenteritis, upper gastrointestinal bleeding and AKI) and 4 (9%) died (2 cases of pneumonia, 1 COVID 19 infection and 1 cerebro-vascular accident). Overall response rate was 59% (27/46); 8 Pts (17%) achieved complete or very good partial response (CR/VGPR), 19 Pts (41%) achieved partial response (PR) and 12 Pts (30%) had stable disease (SD). The median PFS was 6.6 [95% CI 2.9 - 10.3] months (Figure 1a). Median duration of response (DOR) was 10.8 months. Median OS was not reached; 1-year overall survival was 81.6±6.7% (Figure 1a). One-year OS was significantly better for responders (89.3±7.3%) than non-responders (72.2±10.7%), p=0.015 ( figure 1b). Conclusions: IPd combination with a twice-weekly ixazomib induction provided an all-oral safe and efficacious therapy in triple-exposed RRMM Pts, most of whom were refractory to both DARA and LEN. Response rates and PFS are encouraging, compared to parenteral PI and IMiD combination regimens in TCE/TCR MM, with a favorable safety profile and convenience, especially among an elderly and frail population with relapsed myeloma.