A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma.

BACKGROUND: The first-in-class brain-penetrating synthetic hydroxylated lipid idroxioleic acid (2-OHOA; sodium 2-hydroxyoleate), activates sphingomyelin synthase expression and regulates membrane-lipid composition and mitochondrial energy production, inducing cancer cell autophagy. We report the findings of a multicentric first-in-human Phase 1/2A trial (NCT01792310) of 2-OHOA, identifying the maximum tolerated dose (MTD) and assessing safety and preliminary efficacy. METHODS: We performed an open-label, non-randomised trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of daily oral treatment with 2-OHOA monotherapy (BID/TID) in 54 patients with glioma and other advanced solid tumours. A dose-escalation phase using a standard 3 + 3 design was performed to determine safety and tolerability. This was followed by two expansion cohorts at the MTD to determine the recommended Phase-2 dose (RP2D). RESULTS: In total, 32 recurrent patients were enrolled in the dose-escalation phase (500-16,000 mg/daily). 2-OHOA was rapidly absorbed with dose-proportional exposure. Treatment was well-tolerated overall, with reversible grade 1-2 nausea, vomiting, and diarrhoea as the most common treatment-related adverse events (AEs). Four patients had gastrointestinal dose-limiting toxicities (DLTs) of nausea, vomiting, diarrhoea (three patients at 16,000 mg and one patient at 12,000 mg), establishing an RP2D at 12,000 mg/daily. Potential activity was seen in patients with recurrent high-grade gliomas (HGG). Of the 21 patients with HGG treated across the dose escalation and expansion, 5 (24%) had the clinical benefit (RANO CR, PR and SD >6 cycles) with one exceptional response lasting >2.5 years. CONCLUSIONS: 2-OHOA demonstrated a good safety profile and encouraging activity in this difficult-to-treat malignant brain-tumour patient population, placing it as an ideal potential candidate for the treatment of glioma and other solid tumour malignancies. CLINICAL TRIAL REGISTRATION: EudraCT registration number: 2012-001527-13; Clinicaltrials.gov registration number: NCT01792310.

Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients.

BACKGROUND & AIMS: Due to the poor eradication rates of standard triple therapy, the addition of bismuth salts has been proposed for first-line eradication of Helicobacter pylori. We assessed the effectiveness and safety of the combination of bismuth and the standard, clarithromycin-containing triple therapy in eradication of H pylori infection, using data from a large multi-center registry. METHODS: We performed an interim analysis of data from the European Registry on H pylori Management, a prospective trial registering clinical data and outcomes from infected patients from 27 countries in Europe since 2013. We extracted data on 1141 treatment-naïve patients who received first-line treatment with bismuth salts (240 mg) and a proton pump inhibitor (57% received esomeprazole, 18% received omeprazole, 11% received pantoprazole, and 14% received rabeprazole), amoxicillin (1 g), and clarithromycin (500 mg), all taken twice daily. RESULTS: Intention to treat and per-protocol rates of eradication were 88% and 94%, respectively. Intention to treat eradication increased to 93% in patients who received 14-day treatments. Adverse events occurred in 36% of patients; 76% of these events were mild, with a mean duration of 6 days. In multivariate analysis, eradication was associated with treatment compliance (odds ratio [OR], 13.0), a double dose (equivalent to 40 mg omeprazole) of proton pump inhibitor (OR, 4.7), and 14-day duration of treatment (OR, 2.0). CONCLUSIONS: In an analysis of data from a large multi-center registry, we found the addition of bismuth to 14-day standard triple therapy with clarithromycin and amoxicillin to eradicate H pylori infection in more than 90% of patients, based on intention to treat analysis, with an acceptable safety profile and level of adherence. ClinicalTrials.gov no: NCT02328131.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain.

INTRODUCTION: Cure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern. The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. MATERIALS AND METHODS: Multicentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. RESULTS: One-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DISCUSSION: Gastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

Prospective, study comparing the accuracy of two different stool antigen tests (Premier Platinum HpSA and novel ImmunoCard STAT! rapid test) for the diagnosis of Helicobacter pylori infection.

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.

Meta-analysis of three-in-one single capsule bismuth-containing quadruple therapy for the eradication of Helicobacter pylori.

BACKGROUND: Bismuth-containing quadruple therapy has been suggested as first-line and rescue alternative for Helicobacter pylori eradication. Our objective was to perform a meta-analysis evaluating the efficacy and safety of single capsule Pylera® (bismuth, metronidazole, and tetracycline) plus a proton-pump inhibitor (PPI) in any line of treatment. METHODS: Studies were selected up to October 2018. Outcomes were eradication and adverse events (AEs) rates pooled using the generic inverse variance method. RESULTS: In total, 30 studies (6482 patients) were included in the systematic review. The intention-to-treat (ITT) efficacy was 90% (95% CI: 87%-92%, 21 studies, I2  = 88%) in first-line therapy, 89% (95% CI: 86%-93%, 12 studies, I2  = 78%) in second-line and 82% (95% CI: 78%-87%, nine studies, I2  = 60%) in third-line; with no differences by the type or dosage of PPI used. For metronidazole-resistant infection, the ITT efficacy as first-line therapy was 93% (95% CI: 90%-96%, six studies, I2  = 0%). In second-line therapies where patients had been previously treated with clarithromycin, the ITT efficacy was 90% (95% CI: 87%-93%, 11 studies, I2  = 78%). The overall incidence of AEs was 43% (95% CI: 35%-50%, 24 studies, I2  = 92%) and they were mostly mild. In nearly 3% of the cases, treatment was interrupted due to AEs. CONCLUSIONS: A 10-day treatment with Pylera® achieved an effective eradication rate of approximately 90% both in first- and second-line therapy. This applies regardless of the type and dose of the PPI, in patients with clarithromycin- or metronidazole-resistant strains, and in those previously treated with clarithromycin.

Protocol of the European Registry on the management of Helicobacter pylori infection (Hp-EuReg).

INTRODUCTION: Helicobacter pylori selectively infects the human stomach, being the most prevalent chronic infection in the world. H pylori presence causes chronic gastritis in 100% of infected patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease, and gastric cancer; it is for this reason that from a public health standpoint, it is considered a high-impact pathogen, responsible of a significant morbidity and mortality. Nowadays, there are consensus and clinical guidelines regarding the infection management at a European level and in most of European countries, but no data have shown the level of implementation of these recommendations. The high costs that this infection carries both socially and to the health system require the continuous and systematic assessment of the diagnostic and treatment strategies, as well as the accessibility to diagnostic methods and most efficient drugs. AIM: To register the diagnosis, management strategies, and treatment of H pylori-infected adult patients in the Digestive Services outpatient clinics throughout Europe. METHODS: Noninterventionist prospective multicentre international Registry promoted by the European Helicobacter and Microbiota Study Group. National Coordinators will select recruiting gastroenterologists in their country that will register the H pylori-related routine clinical practice consultations they receive in an electronic case report form (e-CRF) provided by AEG-REDCap. Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation, and outcome data. The database will allow researchers to perform specific subanalyses after approval by the Scientific Committee of the study.

Spanish primary care survey on the management of Helicobacter pylori infection and dyspepsia: Information, attitudes, and decisions.

INTRODUCTION: Dyspepsia and Helicobacter pylori are two of the most relevant digestive conditions in primary care. Several consensuses on the subject have been published, but the assimilation/implementation of these guidelines is uncertain. AIMS AND METHODS: To evaluate the attitudes, perceptions, limitations, and adherence to recommendations of Spanish primary care physicians using an open online survey. Responses were anonymously codified. Estimated margin of error was 3.4%. Responses were weighted by province, gender, age, and type of practice. Survey was performed using the AEG-REDCap platform. RESULTS: A total of 1445 responses, received between December 2017 and April 2018, were analyzed. Women represented 54%, and the average age was 48 years; 59% were from urban context, 20% from semi-urban, and 21% from rural; 93% provided public practice. Over 40% had read at least one Maastricht consensus (24% Maastricht V), and 34% had attended a course related to H. pylori. 16% reported no direct access to any validated diagnostic method, only 44% to urea breath test, and 33% did not systematically refer to eradication confirmation test. The first-line treatment of choice was standard triple therapy in 56%, followed by concomitant therapy (28%). Only 20% of physicians had optimal adherence to recommendations. CONCLUSION: Even though some improvements from guidelines have been partially incorporated, the level of penetration of recommendations is still poor and delayed. To provide optimal primary care, the barriers for implementation, access to diagnostic tests and to continuous medical education, should be removed. Rigorous dissemination, implementation, and evaluation programs are desired in future consensuses.

Corrigendum: Research to the N-Power: The Strengths of Networked Clinical Collaboration in Spain.

This corrects the article DOI: 10.1038/ajg.2017.416.

Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. DESIGN: Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. RESULTS: A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (ß -0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy. CONCLUSION: Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.

Helicobacter Pylori Treatment Results in Slovenia in the Period 2013-2015 as a Part of European Registry on Helicobacter Pylori Management.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in the world affecting over 50% of the world's population. H. pylori is a grade I carcinogen, responsible for the development of 89 % of noncardia gastric cancers. In the present study we analyzed the data for H. pylori eradication treatments in Slovenia. PATIENTS AND METHODS: Slovenia is a part of the European Registry on Helicobacter pylori Management from the beginning. In seven medical institutions data for H. pylori eradication treatments was collected for 1774 patients from April 16th 2013 to May 15th 2016. For further modified intention to treat (mITT) analysis 1519 patients were eligible and for per protocol (PP) analysis 1346 patients. RESULTS: Patients' dropout was 11.4%. Eradication rate for 7 day triple therapy with proton pump inhibitor (PPI) + Clarithromycin (C) + Amoxicillin (A) was 88.7% PP and 72.0% mITT; for PPI + C + Metronidazole (M) 85.2% PP and 84.4% mITT. Second line 14 day therapy PPI + A + Levofloxacin had 92.3% eradication rate PP and 87.1% mITT. Ten to fourteen day Bismuth quadruple therapy was the therapy in difficult to treat patients. At the end all patients that adhered to prescribed regimens were cured of their H. pylori infection. CONCLUSIONS: High dropout rate deserves further analysis. Slovenia is still a country with < 15% H. pylori resistance to clarithromycin, triple therapy with PPI plus two antibiotics reaches PP eradication rate > 85%, but mITT eradication rates are suboptimal.

Optimization strategies aimed to increase the efficacy of H. pylori eradication therapies.

BACKGROUND: As with any other infectious disease, we should aim for treatments offering ≥90% Helicobacter pylori eradication rates in clinical practice. AIM: To summarize optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. METHODS: A systematic bibliographic search (in PubMed up to August 2016) was designed to identify studies investigating optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. RESULTS: The most direct way to optimize a treatment is using higher doses of drugs unless it has been shown that lower doses are equally effective. Similarly, prescriptions should use 14-day duration unless a shorter scheme has been shown locally to be equally effective. Double-dose proton-pump inhibitor therapy is recommended for triple therapy and may probably increase the efficacy of nonbismuth concomitant regimen as well. The efficacy of triple therapies in the presence of resistance can be significantly improved by the addition of bismuth salts, which offer an additive effect in combination with antibiotics. Overall, probiotics seem to reduce antibiotic side effects, but the increase in eradication rates is not so evident; therefore, they cannot be generally recommended for clinical practice yet. CONCLUSIONS: Using potent acid inhibition and/or higher antibiotic doses-especially by increasing the number of daily intakes-and lengthening treatments up to 14 days improves efficacy in most regimens and should be generally recommended. Triple therapies can be efficiently improved by the addition of bismuth salts, turning them into quadruple therapies. Finally, some treatments will require a combination of optimization strategies to significantly improve results.

Efficacy and safety of rifaximin associated with standard triple therapy (omeprazole, clarithromycin and amoxicillin) for H. pylori eradication: A phase IV pilot clinical trial.

BACKGROUND: A progressive decrease in Helicobacter pylori eradication rates has been described over the years, driving the need for new antibiotic treatments. AIM: To evaluate the efficacy and safety of the addition of rifaximin (Spiraxin®) to standard triple therapy (omeprazole, amoxicillin and clarithromycin) for the eradication of H. pylori. METHODS: Independent prospective clinical trial (EUDRACT no.: 2013-001080-23). Forty consecutive adult patients were included with H. pylori infection, dyspeptic symptoms and naive to eradication treatment. A full blood test was performed in the first five patients enrolled to evaluate the safety of the treatment. H. pylori eradication was confirmed with the 13C-urea breath test at least four weeks after the end of treatment with rifaximin 400mg/8h, clarithromycin 500mg/12h, amoxicillin 1g/12h and omeprazole 20mg/12h for 10 days. RESULTS: Forty patients were consecutively enrolled, 53% woman, mean age 44 years. Indication for eradication: 60% non-investigated dyspepsia, 38% functional dyspepsia and 2% gastric ulcer. Four patients did not attend the eradication confirmatory breath test. The eradication rate was 61% (95% CI: 45-77%) for the protocol and 55% (40-70%) for intention-to-treat. About 76% of the patients experienced adverse events (35% diarrhea, 14% nausea and 24% metallic taste), none of which was serious. The blood tests did not show significant alterations. CONCLUSION: Acceptable H. pylori eradication rates are not achieved with rifaximin associated with standard triple therapy for 10 days.

Sequential versus standard triple first-line therapy for Helicobacter pylori eradication.

BACKGROUND: Non-bismuth quadruple sequential therapy (SEQ) comprising a first induction phase with a dual regimen of amoxicillin and a proton pump inhibitor (PPI) for five days followed by a triple regimen phase with a PPI, clarithromycin and metronidazole for another five days, has been suggested as a new first-line treatment option to replace the standard triple therapy (STT) comprising a proton pump inhibitor (PPI), clarithromycin and amoxicillin, in which eradication proportions have declined to disappointing levels. OBJECTIVES: To conduct a meta-analysis of randomised controlled trials (RCTs) comparing the efficacy of a SEQ regimen with STT for the eradication of H. pylori infection, and to compare the incidence of adverse effects associated with both STT and SEQ H. pylori eradication therapies. SEARCH METHODS: We conducted bibliographical searches in electronic databases, and handsearched abstracts from Congresses up to April 2015. SELECTION CRITERIA: We sought randomised controlled trials (RCTs) comparing 10-day SEQ and STT (of at least seven days) for the eradication of H. pylori. Participants were adults and children diagnosed as positive for H. pylori infection and naïve to H. pylori treatment. DATA COLLECTION AND ANALYSIS: We used a pre-piloted, tabular summary to collect demographic and medical information of included study participants as well as therapeutic data and information related to the diagnosis and confirmatory tests.We evaluated the difference in intention-to-treat eradication between SEQ and STT regimens across studies, and assessed sources of the heterogeneity of this risk difference (RD) using subgroup analyses.We evaluated the quality of the evidence following Cochrane standards, and summarised it using GRADE methodology. MAIN RESULTS: We included 44 RCTs with a total of 12,284 participants (6042 in SEQ and 6242 in STT). The overall analysis showed that SEQ was significantly more effective than STT (82% vs 75% in the intention-to-treat analysis; RD 0.09, 95% confidence interval (CI) 0.06 to 0.11; P < 0.001, moderate-quality evidence). Results were highly heterogeneous (I² = 75%), and 20 studies did not demonstrate differences between therapies.Reporting by geographic region (RD 0.09, 95% CI 0.06 to 0.12; studies = 44; I² = 75%, based on low-quality evidence) showed that differences between SEQ and STT were greater in Europe (RD 0.16, 95% CI 0.14 to 0.19) when compared to Asia, Africa or South America. European studies also showed a tendency towards better efficacy with SEQ; however, this tendency was reversed in 33% of the Asian studies. Africa reported the closest risk difference (RD 0.14 , 95% 0.07 to 0.22) to Europe among studied regions, but confidence intervals were wider and therefore the quality of the evidence showing SEQ to be superior to STT was reduced for this region.Based on high-quality evidence, subgroup analyses showed that SEQ and STT therapies were equivalent when STT lasted for 14 days. Although, overall, the mean eradication proportion with SEQ was over 80%, we noted a tendency towards a lower average effect with this regimen in the more recent studies (2008 and after); weighted linear regression showed that the efficacies of both regimens evolved differently over the years, having a higher reduction in the efficacy of SEQ (-1.72% yearly) than in STT (-0.9% yearly). In these more recent studies (2008 and after) we were also unable to detect the superiority of SEQ over STT when STT was given for 10 days.Based on very low-quality evidence, subgroup analyses on antibiotic resistance showed that the widest difference in efficacy between SEQ and STT was in the subgroup analysis based on clarithromycin-resistant participants, in which SEQ reached a 75% average efficacy versus 43% with STT.Reporting on adverse events (AEs) (RD 0.00, 95% CI -0.02 to 0.02; participants = 8103; studies = 27; I² = 26%, based on high-quality evidence) showed no significant differences between SEQ and STT (20.4% vs 19.5%, respectively) and results were homogeneous.The quality of the studies was limited due to a lack of systematic reporting of the factors affecting risk of bias. Although randomisation was reported, its methodology (e.g. algorithms, number of blocks) was not specified in several studies. Additionally, the other 'Risk of bias' domains (such as allocation concealment of the sequence randomisation, or blinding during either performance or outcome assessment) were also unreported.However, subgroup analyses as well as sensitivity analyses or funnel plots indicated that treatment outcomes were not influenced by the quality of the included studies. On the other hand, we rated 'length of STT' and AEs for the main outcome as high-quality according to GRADE classification; but we downgraded 'publication date' quality to moderate, and 'geographic region' and 'antibiotic resistance' to low- and very low-quality, respectively. AUTHORS' CONCLUSIONS: Our meta-analysis indicates that prior to 2008 SEQ was more effective than STT, especially when STT was given for only seven days. Nevertheless, the apparent advantage of sequential treatment has decreased over time, and more recent studies do not show SEQ to have a higher efficacy versus STT when STT is given for 10 days.Based on the results of this meta-analysis, although SEQ offers an advantage when compared with STT, it cannot be presented as a valid alternative, given that neither SEQ nor STT regimens achieved optimal efficacy ( ≥ 90% eradication rate).

IV Spanish Consensus Conference on Helicobacter pylori infection treatment. / IV Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori.

Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended.

[European Registry on the management of Helicobacter pylori infection (Hp-EuReg protocol): The first results of Russian centers].

AIM: To assess the clinical practice of diagnosis and treatment in patients with Helicobacter pylori infection and to compare this practice with the international guidelines in the European Registry on the management of Helicobacter pylori infection, Hp-EuReg protocol), a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group. MATERIALs AND METHODS: The data of 813 patients infected with H. pylori and entered in the Hp-EuReg register by the Russian centers in 2013-2015 were analyzed. RESULTS: The most common methods for the primary diagnosis of H. pylori infection are histology (40.3%), rapid urease test (35.7%), and serology (17.2%). The duration of H. pylori eradication therapy was 7, 10, and 14 days in 18.0, 49.3, and 25.1%, respectively. To monitor the effectiveness of treatment, the investigators used a histological examination (34%), a urea breath test (27.3%), H. pylori stool antigen (22.8%), and a rapid urease test (16.3%). A serological test was carried out in 2.5% of the cases. No monitoring was done in 13.5% of the patients. The average eradication efficiency was 82.6%. If the therapy was ineffective, 80% of physicians did not intend to prescribe a new cycle of treatment. CONCLUSION: Significant differences were found between clinical practice and the current guidelines.

Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

BACKGROUND: Helicobacter pylori eradication is a challenge in penicillin allergy. AIM: To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. METHODS: Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. RESULTS: In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p < 0.05). Compliance with treatment was 94 and 98 %, respectively. Adverse events were reported in 14 % with both regimens (all mild). (2) Second-line treatment: Intention-to-treat eradication rate with omeprazole-clarithromycin-levofloxacin was 64 % both after triple and quadruple failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. CONCLUSION: In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice.

OBJECTIVES: No trial has compared non-bismuth quadruple 'sequential' and 'concomitant' regimens in settings with increasing clarithromycin rates. The study aims to compare the effectiveness and safety of these therapies for Helicobacter pylori treatment. DESIGN: Prospective randomised clinical trial in 11 Spanish hospitals. Patients naïve to eradication therapy with non-investigated/functional dyspepsia or peptic ulcer disease were included. Randomised (1:1) to sequential (omeprazole (20 mg/12 h) and amoxicillin (1 g/12 h) for 5 days, followed by 5 days of omeprazole (20 mg/12 h), clarithromycin (500 mg/12 h) and metronidazole (500 mg/12 h)), or concomitant treatment (same drugs taken concomitantly for 10 days). Eradication was confirmed with (13)C-urea breath test or histology 4 weeks after treatment. Adverse events (AEs) and compliance were evaluated with questionnaires and residual medication count. RESULTS: 338 consecutive patients were randomised. Mean age was 47 years, 60% were women, 22% smokers and 20% had peptic ulcer. Concomitant and sequential eradication rates were, respectively, 87% vs 81% by intention-to-treat (p=0.15) and 91% vs 86% (p=0.131) per protocol. Respective compliances were 83% vs 82%. Treatment-emergent AEs were reported in 59% of patients (no differences found between treatments). AEs were mostly mild (60%), and average length was 6.1 days, causing discontinuation only in 12 patients. Multivariate analysis: 'concomitant' treatment showed an OR of 1.5 towards better eradication rate in a borderline significance CI (95% CI 0.9 to 2.8). CONCLUSIONS: Concomitant therapy led to a non-statistically significant advantage (5%) over sequential therapy, coming closer to 90% cure rates. Both therapies showed an acceptable safety profile. ClincialTrials.gov: NCT01273441.