The Application of High-Dose Proton Pump Inhibitor Induction Treatment before Dual Therapy for Helicobacter pylori Eradication: An Open-Label Random Trial

Round 1

Reviewer 1 Report

In the present article, the authors performed prospective, randomized, open-label trial to evaluate whether high-dose rabeprazole induction treatment before dual eradication therapy and taking 14-day rabeprazole and amoxicillin simultaneously at meal time and bedtime could achieve an acceptable H. pylori eradication rate and drug compliance. This report suggests newly regimen with the result indicating that high-frequency rabeprazole could improve the H. pylori eradication rate with dual therapy even with taking the drugs simultaneously.

Minor comment:

Line 136 and 146

The authors should describe the information about reference No. 28 and 29 in the reference list.

Author Response

Question 1: Line 136 and 146

The authors should describe the information about reference No. 28 and

29 in the reference list.

Answer: Thanks for pointing out the missed references. We add these two missed references and adjust the sequence of reference as below:

Reference No 28 into No 21

21. de Boer WA, Thys JC, Borody TJ, et al. Proposal for use of a standard side effect scoring system in studies exploring Helicobacter pylori treatment regimens. Eur J Gastroenterol Hepatol 1996;8:641–643.

Reference No 29 into No 23

23. Liou JM, Chang CY, Chen MJ, et al. The primary resistance of Helicobacter pylori in Taiwan after the national policy to restrict antibiotic consumption and its relation to virulence factors –A nationwide study. PLoS ONE. 2015;10:e0124199.

Reviewer 2 Report

In this study the AA compared efficacy of a 14 day Rabepraziole/amoxicillin modified dual therapy versus a traditional 14 day Rabeprazole/Amoxcicillin/Clarithromycin triple therapy for H. pylori infection.
In detail, modified dual therapy comprised an oral Rabeprazole (20 mg qid) pre-treatment intake  for 3 days   followed by a  combined and simultaneous Rabeprazole (20 mg qid) and Amoxicillin (500 mg qid)  administration (breakfast, lunch, dinner, and bedtime) for 14 days. The PPI-pretreatment was justified by attempt to increase intragastric pH and to induce H. pylori to replicative and more antimicrobial-susceptible status whilst the simultaneous intake of PPI and Amoxicillin was justified by attempt to increase patient’s compliance.

The results found higher eradication rates by using  modified dual  respect to triple therapy (91.7% vs. 77.1% at ITT; 94.3% vs. 84.3%, per PP analysis) without reaching statistical significance.

The study appears of clinical interest and the results confirm previous findings about the role, still significant,  of dual therapy in the management of H. pylori infection.

Criticisms

The study enrolled very small patient’s sample. Therefore, the results (with wide 95% CI)   must be considered with caution.

The search  found the now suboptimal and unacceptable efficacy of classic triple therapy eleven in Southern-East Asiatic  countries. This last aspect would be underlined in discussion.

Treatment costs must be reported.

Author Response

Thanks for reviewer's valuable comments.

Reviewer 2 has three questions.

Question 1: The study enrolled very small patient’s sample. Therefore, the results (with wide 95% CI) must be considered with caution.

Answer: We agree that a small sample size is a limitation which will induce statistical bias. We have added this shortcoming and “a wide range of 95% CI in the results must be considered with caution” in the limitation section. The source of the subjects was a community UBT screening for H. pylori infection. Because the coronavirus disease 2019 pandemic developed and removing face masks was forbidden, UBT screening was conducted for a long period in this study. Although the minimal number of subjects was calculated at the start of the study, the statistical power was not strong when only a minimal number of subjects were included. A type II error may be made in the present of results. We added this description in the limitation section. (Page 7, limitation section)

Question 2: The search found the now suboptimal and unacceptable efficacy of classic triple therapy eleven in Southern-East Asiatic countries. This last aspect would be underlined in discussion.

Answer: We add the statement in the discussion section as below:

“Because of the increasing clarithromycin resistance of H. pylori, the eradication rate of clarithromycin-based triple therapy is now suboptimal and unacceptable efficacy in some Southern-East Asiatic countries. Although antimicrobial susceptibility testing is recommended for the choice of eradication regimens in regions of high antibiotic resistance, it is not available in some areas. A treatment design combining PPI with low resistance drug, such as amoxicillin, is more practical without the need for susceptibility testing.” (Page 6, result section)

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Question 3: Treatment costs must be reported.

Answer: The unit prices of amoxicillin (500 mg), rabeprazole (20 mg) and clarithromycin (500 mg) are 4, 11 and 16 new Taiwan dollar (NTD) separately. The gross prices of HDDT regimens and CATT regimens are 972 NTD (about 29.77 EUR or 35.03 USD) and 980 NTD (about 30.01 EUR or 35.32 USD). We add treatment costs description in the result section. (Page 6)