Reviewer ’s report  
 
Title:  Preventive effect of ecabet sodium on low -dose aspirin -induced small intestinal mucosal 
injury: A randomized, double -blind, pilot study  
 
Version: 2 Date: 20 Nov 2018 
 
Reviewer:  Takuma  Higurashi  
 
Reviewer’s report:  
 
The authors prospectively analyzed high -dose ecabet sodium affects low -dose aspirin -induced 
small intestinal mucosal injury in healthy volunteers. The authors showed a significant difference 
in the median number of small intestinal lesions between baseline  and two weeks after low -dose 
aspirin administration in group A, but not in group B. Furthermore, they showed , in group B, 
although the median numberof lesions in the first tertile of the small intestine did not increase 
two weeks after low -dose aspirin a dministration. Then, they concluded ecabet sodium had a 
preventive effect on low -dose aspirin -induced small intestinal mucosal injury in the upper part of 
the small intestine.  
 
This is well written study and novel information, however, this study has some l imitations, in the 
following areas.  
 
 
<Major＞ 
 
1. What is the base of sample size? The authors should describe sample size calculation.  
 
2. What is the basis of dose setting of ecabet sodium?  The authors should describe about it .  
 
3. The authors compared wit h before and after intervention in each groups. However, I 
guess this study design is comparison between parallel groups? Then authors should 
compare the small instestinal lesion after invention between group A and group B.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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.  
No 
 
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:  
 
Needs some language corrections before being published  
 
Declaration of competing interes ts 
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 publ ication 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 g ive 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 rep ort 
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 wish 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:  Preventive effect of ecabet sodium on low -dose aspirin -induced small intestinal mucosal 
injury: A randomized, double -blind, pilot study  
 
Version: 2 Date: 20 Nov 2018 
 
Reviewer:  Takuma  Higurashi  
 
Reviewer’s report:  
 
The authors prospectively analyzed high -dose ecabet sodium affects low -dose aspirin -induced 
small intestinal mucosal injury in healthy volunteers. The authors showed a significant difference 
in the median number of small intestinal lesions between baseline  and two weeks after low -dose 
aspirin administration in group A, but not in group B. Furthermore, they showed , in group B, 
although the median numberof lesions in the first tertile of the small intestine did not increase 
two weeks after low -dose aspirin a dministration. Then, they concluded ecabet sodium had a 
preventive effect on low -dose aspirin -induced small intestinal mucosal injury in the upper part of 
the small intestine.  
 
This is well written study and novel information, however, this study has some l imitations, in the 
following areas.  
 
 
<Major＞ 
 
1. What is the base of sample size? The authors should describe sample size calculation.  
 
2. What is the basis of dose setting of ecabet sodium?  The authors should describe about it .  
 
3. The authors compared wit h before and after intervention in each groups. However, I 
guess this study design is comparison between parallel groups? Then authors should 
compare the small instestinal lesion after invention between group A and group B.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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.  
No 
 
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:  
 
Needs some language corrections before being published  
 
Declaration of competing interes ts 
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 publ ication 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 g ive 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 rep ort 
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 wish 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:  Preventive effect of ecabet sodium on low -dose aspirin -induced small intestinal mucosal 
injury: A randomized, double -blind, pilot study  
 
Version: 2 Date: 20 Nov 2018 
 
Reviewer:  Takuma  Higurashi  
 
Reviewer’s report:  
 
The authors prospectively analyzed high -dose ecabet sodium affects low -dose aspirin -induced 
small intestinal mucosal injury in healthy volunteers. The authors showed a significant difference 
in the median number of small intestinal lesions between baseline  and two weeks after low -dose 
aspirin administration in group A, but not in group B. Furthermore, they showed , in group B, 
although the median numberof lesions in the first tertile of the small intestine did not increase 
two weeks after low -dose aspirin a dministration. Then, they concluded ecabet sodium had a 
preventive effect on low -dose aspirin -induced small intestinal mucosal injury in the upper part of 
the small intestine.  
 
This is well written study and novel information, however, this study has some l imitations, in the 
following areas.  
 
 
<Major＞ 
 
1. What is the base of sample size? The authors should describe sample size calculation.  
 
2. What is the basis of dose setting of ecabet sodium?  The authors should describe about it .  
 
3. The authors compared wit h before and after intervention in each groups. However, I 
guess this study design is comparison between parallel groups? Then authors should 
compare the small instestinal lesion after invention between group A and group B.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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.  
No 
 
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:  
 
Needs some language corrections before being published  
 
Declaration of competing interes ts 
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 publ ication 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 g ive 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 rep ort 
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 wish 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