Reviewer ’s report  
 
Title: Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth  
quadruple therapy for the first -line eradication of Helicobact er pylori: a prospective, multi center,  
randomized clinical trial  
 
Version: 0 Date: 03 Feb 2016  
 
Reviewer: Jean Charles Delchier  
 
Reviewer's report:  
 
General  comment :  
 
 
This manuscript reports an important prospective, multicenter, randomized study including 390 
patients comparing 10 day sequential  therapy with 14 day modified bismuth quadruple therapy( 
PPI-bismuth - tetracycline -amoxicillin).  
 
 
 Results are rather disappoi nting  as neither the control arm(SQT) nor the test arm (bismuth 
quadruple) reached optimal results (per protocol > 90%).  
 
 
This study had probably too much objectives: to demonstrate efficacy of the amox -tetracycline 
bismuh quadruple therapy, to search for a well tolerated quadruple therapy…  
 
 
The selected control arm (SQT) was known as not optimal as discussed in the background 
section ( p 5 -6)  due to the high level of clarithromycin and metronidazole resistance in Korea. It 
is now well admitted that non bi smuth concomitant quadruple therapy(PPI -claithromycin -
metronidazole -amoxicllin) is more efficient than SQT and should become the reference  non 
bismuth treatment in countries with a high level of clarithromycin resistance.  
 
 
It would have been more interesti ng to compare different  bismuth quadruple therapy for 
example the most popular  14 day PPI -bismuth - tetracyclin - metronidazole versus 14 day  PPI -
tetracycline -amoxicillin -bismuth or 14 day  PPI -tetracycline b.i.d -amoxicillin b.i.d -bismuth vs 
14 day  PPI -tetracycline b.i.d -amoxicillin b.i.d -bismuth b.i.d  vs  14 day  PPI -tetracycline q.d.s -
amoxicillin b.i.d -bismuth t.d.s. This last fprmulation was indeed used in the trial by Chi et all 
(ref 23) who reported favorable results in comparison  with the amox -tetra- bismuth quadruple 
therapy.  
 
 
In summary, the choice of the treatment arms should be discussed in the paper.  
 
Minor comments  
 
- The authors should mention the interest of the new gallenic  formulation including bismuth salt, 
tetracycline and metronidazo le.  With this formulation administred q.d.s, PP eradication rates in 
first line treatment was always >90%.  
 
 
- ref 18 is misquoted  
 
 
 
 
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, conside ring 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'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wis h to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth  
quadruple therapy for the first -line eradication of Helicobact er pylori: a prospective, multi center,  
randomized clinical trial  
 
Version: 0 Date: 03 Feb 2016  
 
Reviewer: Jean Charles Delchier  
 
Reviewer's report:  
 
General  comment :  
 
 
This manuscript reports an important prospective, multicenter, randomized study including 390 
patients comparing 10 day sequential  therapy with 14 day modified bismuth quadruple therapy( 
PPI-bismuth - tetracycline -amoxicillin).  
 
 
 Results are rather disappoi nting  as neither the control arm(SQT) nor the test arm (bismuth 
quadruple) reached optimal results (per protocol > 90%).  
 
 
This study had probably too much objectives: to demonstrate efficacy of the amox -tetracycline 
bismuh quadruple therapy, to search for a well tolerated quadruple therapy…  
 
 
The selected control arm (SQT) was known as not optimal as discussed in the background 
section ( p 5 -6)  due to the high level of clarithromycin and metronidazole resistance in Korea. It 
is now well admitted that non bi smuth concomitant quadruple therapy(PPI -claithromycin -
metronidazole -amoxicllin) is more efficient than SQT and should become the reference  non 
bismuth treatment in countries with a high level of clarithromycin resistance.  
 
 
It would have been more interesti ng to compare different  bismuth quadruple therapy for 
example the most popular  14 day PPI -bismuth - tetracyclin - metronidazole versus 14 day  PPI -
tetracycline -amoxicillin -bismuth or 14 day  PPI -tetracycline b.i.d -amoxicillin b.i.d -bismuth vs 
14 day  PPI -tetracycline b.i.d -amoxicillin b.i.d -bismuth b.i.d  vs  14 day  PPI -tetracycline q.d.s -
amoxicillin b.i.d -bismuth t.d.s. This last fprmulation was indeed used in the trial by Chi et all 
(ref 23) who reported favorable results in comparison  with the amox -tetra- bismuth quadruple 
therapy.  
 
 
In summary, the choice of the treatment arms should be discussed in the paper.  
 
Minor comments  
 
- The authors should mention the interest of the new gallenic  formulation including bismuth salt, 
tetracycline and metronidazo le.  With this formulation administred q.d.s, PP eradication rates in 
first line treatment was always >90%.  
 
 
- ref 18 is misquoted  
 
 
 
 
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, conside ring 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'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wis h to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth  
quadruple therapy for the first -line eradication of Helicobact er pylori: a prospective, multi center,  
randomized clinical trial  
 
Version: 0 Date: 03 Feb 2016  
 
Reviewer: Jean Charles Delchier  
 
Reviewer's report:  
 
General  comment :  
 
 
This manuscript reports an important prospective, multicenter, randomized study including 390 
patients comparing 10 day sequential  therapy with 14 day modified bismuth quadruple therapy( 
PPI-bismuth - tetracycline -amoxicillin).  
 
 
 Results are rather disappoi nting  as neither the control arm(SQT) nor the test arm (bismuth 
quadruple) reached optimal results (per protocol > 90%).  
 
 
This study had probably too much objectives: to demonstrate efficacy of the amox -tetracycline 
bismuh quadruple therapy, to search for a well tolerated quadruple therapy…  
 
 
The selected control arm (SQT) was known as not optimal as discussed in the background 
section ( p 5 -6)  due to the high level of clarithromycin and metronidazole resistance in Korea. It 
is now well admitted that non bi smuth concomitant quadruple therapy(PPI -claithromycin -
metronidazole -amoxicllin) is more efficient than SQT and should become the reference  non 
bismuth treatment in countries with a high level of clarithromycin resistance.  
 
 
It would have been more interesti ng to compare different  bismuth quadruple therapy for 
example the most popular  14 day PPI -bismuth - tetracyclin - metronidazole versus 14 day  PPI -
tetracycline -amoxicillin -bismuth or 14 day  PPI -tetracycline b.i.d -amoxicillin b.i.d -bismuth vs 
14 day  PPI -tetracycline b.i.d -amoxicillin b.i.d -bismuth b.i.d  vs  14 day  PPI -tetracycline q.d.s -
amoxicillin b.i.d -bismuth t.d.s. This last fprmulation was indeed used in the trial by Chi et all 
(ref 23) who reported favorable results in comparison  with the amox -tetra- bismuth quadruple 
therapy.  
 
 
In summary, the choice of the treatment arms should be discussed in the paper.  
 
Minor comments  
 
- The authors should mention the interest of the new gallenic  formulation including bismuth salt, 
tetracycline and metronidazo le.  With this formulation administred q.d.s, PP eradication rates in 
first line treatment was always >90%.  
 
 
- ref 18 is misquoted  
 
 
 
 
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, conside ring 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'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wis h to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant