Reviewer’s report
Title: 
Ten-day bismuth-containing quadruple therapy versus 7-day proton pump
inhibitor-clarithromycin containing triple therapy as first-line empirical therapy
for the Helicobacter pylori infection in Korea: A randomized open-label trial
Version: 
0 
Date: 
05 Jul 2020
Reviewer's report:
Kim et al. reported an original article in title "Ten-day bismuth-containing
quadruple therapy versus 7-day proton pump inhibitor-clarithromycin containing
triple therapy as first-line empirical therapy for the Helicobacter pylori infection
in Korea: A randomized open-label trial". They concluded that ten-day BQT had
higher eradication rates compared to that of the 7-day STT as an empirical first-
line treatment for H. pylori eradication in Korea.
The topic is a high originality but less novelty. Some criticizes and suggestion
are list below.
The major comments
1. According to the consensuses after 2017 of Maastricht V/Florence, Taiwan,
and Toronto, optimal treatment of H pylori infection requires local antibiotic
resistance data and PPI based triple therapy needs a 14-day therapy (Gut
2017;66(1):6-30; Helicobacter 2017;22:e12368; Gastroenterology
2016;151(1):51-69.e14.). Therefore, the control group using a 7-day triple
therapy seems to be inappropriate. Do the majority of clinicians using a 7-day
PPI based triple therapy for H. pylori eradication in Korea?
2. Bismuth-containing quadruple therapy usually used for the 2nd line therapy
for H. pylori eradication. The idea for changing it to the first line reagent is
novel. However, based on the result of ITT (74.3%) and high adverse (23.1%) of
BQT, it seems to be hard to accept for the first line therapy.
3. The limitation of this study is lack of antimicrobial susceptibility data. As in
the sample size calculation, you assume the clarithromycin-resistant rate was
20% (may be from local data). BQT could be an alternative choice for the first
line therapy in Korea.
The minor comments
1. Page 11, lines 1-3: "Thus, 134 participants from the STT group and 143 from
the BQT group were included in the modified ITT analysis for the overall
eradication rate." It is not clear.
2. Also in Page 11, lines 4-7: "Overall eradication rates were not significantly
different between the groups (97.8% [131/134 participants] for the STT group
and 98.6% [141/143 participants] for the BQT group; p= 0.676; Table 2)." Do
you mean that to combine the BQT and STT, the eradication rate is equal in
either choosing BQT (98.6%) or STT (97.8%) for the first line therapy? Do you
find the 2nd line therapy (both BQT and STT) had a higher eradication rate that
the first line therapy? Theoretically, it is very rare.
Publons Reviewer Recognition
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No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests below.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Reviewer’s report
Title: 
Ten-day bismuth-containing quadruple therapy versus 7-day proton pump
inhibitor-clarithromycin containing triple therapy as first-line empirical therapy
for the Helicobacter pylori infection in Korea: A randomized open-label trial
Version: 
0 
Date: 
05 Jul 2020
Reviewer's report:
Kim et al. reported an original article in title "Ten-day bismuth-containing
quadruple therapy versus 7-day proton pump inhibitor-clarithromycin containing
triple therapy as first-line empirical therapy for the Helicobacter pylori infection
in Korea: A randomized open-label trial". They concluded that ten-day BQT had
higher eradication rates compared to that of the 7-day STT as an empirical first-
line treatment for H. pylori eradication in Korea.
The topic is a high originality but less novelty. Some criticizes and suggestion
are list below.
The major comments
1. According to the consensuses after 2017 of Maastricht V/Florence, Taiwan,
and Toronto, optimal treatment of H pylori infection requires local antibiotic
resistance data and PPI based triple therapy needs a 14-day therapy (Gut
2017;66(1):6-30; Helicobacter 2017;22:e12368; Gastroenterology
2016;151(1):51-69.e14.). Therefore, the control group using a 7-day triple
therapy seems to be inappropriate. Do the majority of clinicians using a 7-day
PPI based triple therapy for H. pylori eradication in Korea?
2. Bismuth-containing quadruple therapy usually used for the 2nd line therapy
for H. pylori eradication. The idea for changing it to the first line reagent is
novel. However, based on the result of ITT (74.3%) and high adverse (23.1%) of
BQT, it seems to be hard to accept for the first line therapy.
3. The limitation of this study is lack of antimicrobial susceptibility data. As in
the sample size calculation, you assume the clarithromycin-resistant rate was
20% (may be from local data). BQT could be an alternative choice for the first
line therapy in Korea.
The minor comments
1. Page 11, lines 1-3: "Thus, 134 participants from the STT group and 143 from
the BQT group were included in the modified ITT analysis for the overall
eradication rate." It is not clear.
2. Also in Page 11, lines 4-7: "Overall eradication rates were not significantly
different between the groups (97.8% [131/134 participants] for the STT group
and 98.6% [141/143 participants] for the BQT group; p= 0.676; Table 2)." Do
you mean that to combine the BQT and STT, the eradication rate is equal in
either choosing BQT (98.6%) or STT (97.8%) for the first line therapy? Do you
find the 2nd line therapy (both BQT and STT) had a higher eradication rate that
the first line therapy? Theoretically, it is very rare.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests below.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Please review this paper.
user
Reviewer’s report
Title: 
Ten-day bismuth-containing quadruple therapy versus 7-day proton pump
inhibitor-clarithromycin containing triple therapy as first-line empirical therapy
for the Helicobacter pylori infection in Korea: A randomized open-label trial
Version: 
0 
Date: 
05 Jul 2020
Reviewer's report:
Kim et al. reported an original article in title "Ten-day bismuth-containing
quadruple therapy versus 7-day proton pump inhibitor-clarithromycin containing
triple therapy as first-line empirical therapy for the Helicobacter pylori infection
in Korea: A randomized open-label trial". They concluded that ten-day BQT had
higher eradication rates compared to that of the 7-day STT as an empirical first-
line treatment for H. pylori eradication in Korea.
The topic is a high originality but less novelty. Some criticizes and suggestion
are list below.
The major comments
1. According to the consensuses after 2017 of Maastricht V/Florence, Taiwan,
and Toronto, optimal treatment of H pylori infection requires local antibiotic
resistance data and PPI based triple therapy needs a 14-day therapy (Gut
2017;66(1):6-30; Helicobacter 2017;22:e12368; Gastroenterology
2016;151(1):51-69.e14.). Therefore, the control group using a 7-day triple
therapy seems to be inappropriate. Do the majority of clinicians using a 7-day
PPI based triple therapy for H. pylori eradication in Korea?
2. Bismuth-containing quadruple therapy usually used for the 2nd line therapy
for H. pylori eradication. The idea for changing it to the first line reagent is
novel. However, based on the result of ITT (74.3%) and high adverse (23.1%) of
BQT, it seems to be hard to accept for the first line therapy.
3. The limitation of this study is lack of antimicrobial susceptibility data. As in
the sample size calculation, you assume the clarithromycin-resistant rate was
20% (may be from local data). BQT could be an alternative choice for the first
line therapy in Korea.
The minor comments
1. Page 11, lines 1-3: "Thus, 134 participants from the STT group and 143 from
the BQT group were included in the modified ITT analysis for the overall
eradication rate." It is not clear.
2. Also in Page 11, lines 4-7: "Overall eradication rates were not significantly
different between the groups (97.8% [131/134 participants] for the STT group
and 98.6% [141/143 participants] for the BQT group; p= 0.676; Table 2)." Do
you mean that to combine the BQT and STT, the eradication rate is equal in
either choosing BQT (98.6%) or STT (97.8%) for the first line therapy? Do you
find the 2nd line therapy (both BQT and STT) had a higher eradication rate that
the first line therapy? Theoretically, it is very rare.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests below.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
assistant