Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2018-023131 on 28 October 2018. Downloaded from Efficacy of compoundLactobacillus acidophilus tablets combined with quadruple therapy for Helicobacter pylori eradication and its correlation with pH value in the stomach: a study protocol of a randomised, assessor- blinded, single-centre study Wen Ji, Wei-Qing Chen, Xu Tian To cite: Ji W, Chen W-Q, ABSTRACT Strengths and limitations of this study Tian X. Efficacy of compound Introduction Helicobacter pylori (Hp) is an important Lactobacillus acidophilus tablets pathogenic factor for chronic gastritis, peptic ulcer, ► The trial design is prospective, assessor-blinded and combined with quadruple gastric cancer, gastric mucosa-associated lymphoid therapy for Helicobacter randomised controlled, with a large sample size of tissue lymphoma and other diseases. In China, the pylori eradication and its 526. Hp infection rate is high, but the eradication rate is correlation with pH value in the ► The kit for 14C-urea breath test has the advantages decreasing. A large number of literatures have shown stomach: a study protocol of a of simplicity, rapidity, accuracy, no pain, no trauma that the addition of Lactobacillus acidophilus can randomised, assessor-blinded, and no cross-infection. single-centre study. BMJ Open improve the Hp eradication rate and reduce the side ► Lactobacillus acidophilus is expected to become a 2018;8:e023131. doi:10.1136/ effects of antibiotic treatments. At present, the exact new method for precisely eradicating Helicobacter bmjopen-2018-023131 mechanism and curative effect of L. acidophilus in the pylori. Prepublication history for eradication of Hp have not yet been determined, and the ► ► In different stages of this study, special personnel conclusions obtained from relevant meta-analyses at http://bmjopen.bmj.com/ this paper is available online. will be assigned to take charge of related work. To view these files, please visit home and abroad are different. Thus, it is very necessary ► The subjects were unable to perform blind methods the journal online (http:// dx. doi. and urgent to further complete a high-quality, clinical, due to limitations in the characteristics of the study. org/ 10. 1136/ bmjopen- 2018- randomised controlled trial research. If this study is 023131). successful, it can provide a new idea and a plan for Hp eradication therapy. INTRODUCTIon WJ and W-QC contributed Methods and analysis This study is a prospective, equally. randomised controlled, single-blinded, parallel-design As we all know, Helicobacter pylori (Hp) is an trial. We will randomly assign 526 adult patients (≥18 important pathogenic factor for chronic Received 24 March 2018 years but <70 years) with Hp confirmed positive by gastritis, peptic ulcer, gastric cancer, on September 24, 2021 by guest. Protected copyright. Revised 8 September 2018 the kit for 14C-urea breath test. Eligible subjects were gastric mucosa-associated lymphoid tissue Accepted 12 September 2018 randomly divided into two groups (group A and group B), lymphoma and other diseases, and has also with 263 subjects in each group. Group A is a quadruple been recognised by the WHO as the first type therapy group, while group B is an L. acidophilus tablets of pathogenic factor for gastric cancer. Hp combined with quadruple therapy group. All patients infection is currently considered an infec- were examined by gastroscopy, and 50 patients in each tious disease1 and patients should be given © Author(s) (or their group will be placed under gastric pH monitor. The Hp employer(s)) 2018. Re-use 2 eradication rate is the primary outcome. The secondary eradication therapy. permitted under CC BY-NC. No Hp is one of the hot spots in the field of commercial re-use. See rights outcomes include gastric pH situation and adverse drug and permissions. Published by reactions. gastroenteropathy. It has been a long time BMJ. Ethics and dissemination The study protocol for anti-Hp research in our country. In the Department of Gastroenterology, has been approved by the Clinical Research Ethics 1990s, the two or three regimens of Hp erad- Chongqing University Cancer Committees of Chongqing University Cancer Hospital ication treatment experienced a brilliant Hospital &Chongqing Cancer and Chongqing Cancer Hospital (2018[012]). The results period of 90% or higher eradication rate. Institute & Chongqing Cancer from this trial will be submitted for publication in peer- In recent years, however, the eradication Hospital, Chongqing, China reviewed journals and will be presented at national and rate has been decreasing, especially in many international conferences. Correspondence to developed areas and urban populations. Trial registration number ChiCTR17014185; Pre-results. Wen Ji; hellovip5@ 126. com The triple therapy, once known as the ‘gold Ji W, et al. BMJ Open 2018;8:e023131. doi:10.1136/bmjopen-2018-023131 1 Open access BMJ Open: first published as 10.1136/bmjopen-2018-023131 on 28 October 2018. Downloaded from standard’, has an eradication rate that can only reach can clear Hp colonisation in the gerbil stomach in a about 70%,3 and had to be removed from the recom- short time (2 weeks), and the clearance rate reaches mended first-line treatment programme. Even with the about 60%. Yaşar et al13 have reported that Lactobacillus currently recommended quadruple regimen4 5 of proton acidophilus combined with triple therapy can increase pump inhibitor (PPI) + colloidal bismuth + two antibi- Hp eradication rates. ‘The fifth consensus report on otics, it is difficult to achieve an Hp eradication rate of the treatment of helicobacter pylori infection’ also indi- 85% in many populations (85% is the basic requirement cates that studies have shown that supplementation with for internationally accepted eradication rates for recom- microecological agents during eradication of Hp may mended regimens). From 2013 to 2014, the Hp resistance reduce the adverse effects of antibiotics on intestinal rate of 740 patients in 11 provinces and cities of China microecology.14 15 Therefore, L. acidophilus used for was investigated by the Hp group of the digestive diseases anti-Hp treatment may improve the eradication rate of branch of the Chinese Medical Association: the double anti-Hp treatment and reduce the side effects of a large resistance rate of antibiotics was 23.47% and the triple number of antibiotic treatment, and is expected to be a resistance rate was 12.91%.6 The choice and substitution new method of accurate eradication of Hp. of antibiotics are limited in our country, and it is difficult At present, the exact mechanism and curative effect to select antibiotics rationally in empirical treatment. At of probiotics in the eradication of Hp have not yet been present, there is little room for improvement, whether in determined, and the conclusions obtained from relevant the number of combined drugs, dosage or the course of meta-analyses are different in the world.16 17 Whether treatment. With the increase of Hp resistance to antibi- probiotics (L. acidophilus) could improve the eradication otics, some of the previous Hp eradication rates of the rate of Hp or reduce the gastrointestinal side effects of programme will also be reduced. Therefore, it is impera- Hp treatment remains to be confirmed, so it is very neces- tive to develop a new method to precisely eradicate Hp. sary and urgent to further complete high-quality clinical Hp is implanted on the surface of the gastric mucosal research. epithelial cells and covered by a mucus layer, which makes There is also one thing worth noting: antibiotics are eradication difficult. It is difficult for most antimicrobial the core drugs in anti-Hp treatment. The minimal inhibi- agents to penetrate directly through the mucus layer. PPI tory concentration (MIC) of many antibiotics (eg, amoxi- can effectively kill Hp by inhibiting gastric acid secre- cillin) to Hp depends on the pH value of the stomach, and tion and changing the pH value in the stomach. There- the MIC increases when the pH decreases. The desired fore, all currently recommended eradication protocols acid strength requires more than 16 hours of intragastric contain PPI. Bismuth can penetrate the mucus layer and pH >5 within 24 hours. When amoxicillin was included in act directly on Hp, depositing on the cell wall of the Hp the regimen, an intragastric pH >6 could achieve better thalli, which leads to the rupture and death of Hp. In results. pH 5.0–5.5 is also the best pH for L. acidophilus general, PPI and bismuth agents play an auxiliary and growth. Therefore, it is necessary to accurately detect the http://bmjopen.bmj.com/ synergistic role in anti-Hp treatment, while antibiotics pH level in the stomach and explore the most suitable pH still play a central role. Current protocols for the eradi- range in the process of anti-Hp treatment. cation of Hp contain two antibiotics; however, large-dose combination of antibiotics can cause short-term changes 7 8 in the intestinal flora, which may lead to antibiotic resis- METHODS AND ANALYSIS tance, antibiotic-related diarrhoea and severe Clostridium We developed this protocol according to the Standard difficile infection, and the long-term safety of treatment is Protocol Items: Recommendations for Interventional worrisome. Trials.18 The trial is registered at the Chinese Clin- on September 24, 2021 by guest. Protected copyright. The acidic environment in the stomach (pH 2.0 or so) ical Trial Registry (www. chictr. org. cn) with identifier inhibited the growth of most bacteria, forming a unique ChiCTR-INR-17014185. flora structure and microenvironment in the stomach.9 10 Once the structure of the flora in the stomach changes, Objectives an imbalance of the gastrointestinal microenvironment The purposes of this trial are to explore the clinical value will lead to a disease.11 Lactobacillus is the main microbial of probiotic preparation compound L. acidophilus as an flora in the human stomach, and it can be successfully auxiliary treatment for Hp eradication and to find out the colonised in the non-acid region of the stomach.