Comparing the Efficacy of Sequential and Standard Quadruple Therapy for Eradication of H. Pylori Infection

Acta Medica (Hradec Králové) 2020; 63(4): 183–187 https://doi.org/10.14712/18059694.2020.61 © 2020 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Comparing the Efficacy of Sequential and Standard Quadruple Therapy for Eradication of H. Pylori Infection


INTRODUCTION
Helicobacter pylori (H. pylori) infection is a worldwide and chronic infection. Its incidence is related to several factors including rate of acquisition of infection with H. pylori, rate of loss of the infection, and long-term survival of bacteria in the gastric mucosa between infection and eradication (1). H. pylori infection is associated with incidence of gastrointestinal diseases such as peptic ulcer, gastric inflammation and gastric cancer (2). It may lead to dyspeptic symptoms via changing the gastric acid secretion (3,4), post-infective alterating gastroduodenal mucosa and activating inflammation of gastric mucosa (4). The prevalence of H. pylori infection in developing countries is greater compared to developed countries (3). Furthermore, this prevalence varies in different countries and geographic regions of Asia (5). In this regard, prevalence rate in Japan, China, and Singapore is 39%, 58%, and 31%, respectively. Moreover, report of H. pylori infection rate is different in various areas of Iran (6)(7).
Eradicating H. pylori prevents the recurrence of disease, decreases the risk of gastric cancer and heals peptic ulcers (8). In addition, after treating with antibiotics, other H. pylori-associated disorders including chronic atrophic gastritis, intestinal metaplasia and mucosa-associated lymphoid tissue can be regressed (8). However, an important issue in treatment of anti-H. pylori is antibiotic resistance (9) which has an effect on treatment efficacy (10).
Given that prevalence of H. pylori infection in Iran is high (9) and few studies have evaluated efficacy of these two treatments as the first line therapy for H. pylori infection in our country, the aim of current study was comparison the effectiveness of sequential therapy and standard quadruple therapy on eradication of H. pylori infection.

MATERIALS AND METHODS
This clinical trial study was conducted on patients with dyspepsia or gastroduodenal ulcer referred to Shahid Beheshti hospital, Kashan, Iran during 2018. After taking consent from patients, current research was approved by Kashan University of Medical Sciences.
Inclusion and exclusion criteria were as following. Helicobacter pylori eradication was assessed at least 2 months after the end of antibiotic treatment or at least 2 weeks after omeprazole discontinuation via fecal antigen. Information including age, sex, history of H. pylori infection, history of non-steroidal anti-inflammatory drugs and alcohol intake and smoking were extracted from medical records.

STATISTICAL ANALYSIS
Data were entered SPSS, version 19. Chi square test and Fisher exact test were used for analysis of data. P-value < 0.05 was considered statistically significant.

RESULTS
In current study, 160 patients were classified to two groups. The mean age of patients in group A and B was 45.92 ± 14.18 and 41.43 ± 13.61 (p = 0.043).
Other characteristics of patients in two groups are shown in Table 1.
As shown in Table 1, no significant difference was seen between two groups, in terms of characteristics such as sex, smoking, History of H. pylori infection and Taking non-steroidal anti-inflammatory drugs (p > 0.05).
Frequency of H. pylori eradication in two groups is shown in Table 2.
As shown in Table 2, no significant difference was seen between two groups, regarding H. pylori eradication (p > 0.05).
Frequency distribution of side effects in two groups is demonstrated in Table 3. small intestine (28)(29)(30)(31). Moreover, H. pylori infection causes mortality and morbidity with an economic impact, thus requiring a proper therapeutic approach. Physicians usually treat stomach pain and ulcers created by H. pylori via combination of various antibiotics for several days. Recently, increasing resistance to standard antibiotic therapy for H. pylori infection was reported (16)(17)(18)(19)(20)(21)(22). Actually after standard therapy, infection was observed in one of every six patients with peptic ulcer disease. Therefore, H. pylori treatment is a challenge for physicians and no current first-line therapies are capable to treat the infection in all treated individuals (32). Based on findings of recent studies, sequential therapy is identified as first-line therapy in treatment of patients with H. pylori infection (32). The findings of current study showed that the sequential regimen was superior to the quadruple therapy in the treatment of H. pylori infection, although no statistically significant were observed between two groups. In this study 78.8% of patients in sequential group and 68.8% of patients in quadruple diet group have recovered. Vaira et al., assessed sequential therapy versus standard triple therapy for eradication of H. pylori. The findings showed that eradication with sequential therapy was greater than standard therapy in these patients, which was consistent with our study (32).
Sánchez-Delgado et al., assessed ten-day sequential therapy for H. pylori eradication. They selected 139 patients and sequential regime consisted of a 10-day treatment such as a proton pump inhibitor b.d., 1 g b.d. amoxicillin for the first 5 days, followed by a PPI b.d., 500 mg b.d. clarithromycin and 500 mg b.d. metronidazole for the next 5 days. According to findings of this study, eradication was seen in 117 out of 129 patients who returned. It seems that sequential treatment is effective for eradicating H. pylori (33). Zhou et al., in China assessed sequential therapy regimen compared to conventional triple therapy for H. pylori eradication. Then, patients in group A received clarithromycin (500 mg), esomeprazole (20 mg) for the first 5 days, following esomeprazole (20 mg), clarithromycin (500 mg), amoxicillin (1000 mg) for the remaining 5 days. Group B received esomeprazole (20 mg), amoxicillin (1000 mg) for 5 days, followed by clarithromycin (500 mg), esomeprazole (20 mg), and amoxicillin (1000 mg) the remaining 5 days. The findings of this study showed that both treatments can alleviate symptoms in patients. Moreover, they believed that sequential therapy was better than standard As shown in Table 3, the most common side effect in group A and B was bitterness of mouth and nausea, respectively (p < 0.001). Moreover significant differences was observed between two groups, regarding bitterness of mouth (p < 0.001) (Chi square test).
Logistic regression analysis of studied variables is presented in Table 4.
After eliminating confounding effect of independent variables, there was no significant difference between two groups, regarding eradication of H. pylori infection (Table 4).

DISCUSSION
H. pylori infection is not associated with symptoms in 50% of cases. However, some individuals develop inflammation of the gastritis or ulcers in the stomach or upper  (35). Varia et al., reported 7-14 days triple therapy is reducing around the world with unsatisfactory low eradication rate in various country. They believed that sequential therapy is the most effective in first-line therapy and had superiority over standard triple therapy on more than 2300 treated patients. In addition, they reported that the sequential therapy is successful against those clarithromycin-resistant strains that have the A2143G point mutation, which significantly reduces the effectiveness of standard triple therapy (32). The precise mechanism of sequential therapy was unknown. There are several reasons, but all remain unconfirmed at this time.
One of the reasons is that reducing the bacterial density in the stomach via medications including amoxicillin and improving the efficacy of subsequently administered combination such as tinidazole and clarithromycin (36).
In addition, the most common side effects in group A and B was bitterness of mouth and nausea, respectively. Moreover, significant difference was observed between two groups, regarding side effects. Kaboli et al., compared sequential regimen and standard therapy for H. pylori eradication. The findings showed significant difference between two groups, regarding side effects, which was consistent with our study (37). Aminian et al., compared sequential regimen and standard quadruple therapy in patients with dyspepsia. The findings showed that there was significant difference between sequential regimen and standard quadruple regimen, considering side effects (38). This study also was consistent with our study.
It is noteworthy that the eradication rate of Helicobacter pylori in the two treatment groups was compared with controlling confounding variables of age, sex, use of nonsteroidal anti-inflammatory drugs, smoking and family history of Helicobacter pylori infection via logistic regression analysis (Table 4). This caused to control the effect of confounding factors.

CONCLUSION
Although no significant difference was seen between two groups in terms of eradication of H. pylori infection, higher rate of eradication of H. pylori infection was observed in sequential treatment regimens than standard regimens. Therefore, it was considered as a more appropriate treatment regimen compared to standard regimens in first-line therapy of H. pylori infection. In addition, this medication regimen was associated with fewer side effects.