Dear Dr. Rabelo-Silva,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 17 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Madhuradhar Chegondi, MD

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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6. We note that the original protocol that you have uploaded as a Supporting Information file contains an institutional logo. As this logo is likely copyrighted, we ask that you please remove it from this file and upload an updated version upon resubmission.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: Interesting protocol

Some issues should be addressed

1) background in abstract shoudld be shortened

2)methods: it is not clear how randomization will be performed

3)sample calculation is not clear to me>authors should state if they start from some infections rates and go back to others. Moreover it should be performed on primary end point

4) do authors think that subgroup analysis should be performed

Reviewer #2: In this ambitious multicentric trial, the authors wish to investigate if tunneled PICC lines in adult patients provide benefit compared to standard PICC insertion techniques. In this trial, the authors wish to enroll 840 patients in three centers in Brazil and use stratified randomization. The primary outcome variable is the isolated or combined adverse events from PICC lines (infection, thrombosis, obstruction, or dislodgement).

Overall, the study design is pretty straightforward. In the supplemental protocol, the authors mentioned that the study team members inserting the tunnel for clients would be specifically trained. It is fairly ambitious with the amount of funding available to them. But if baseline insertions are part of standard patient management, then it should be feasible.

The authors’ sample size is based on an estimate of a 50% reduction in composite outcomes. This appears very, very optimistic. The authors have not provided any information on how they estimated a 50% reduction. This is important because an inadequately powered study (because of overestimation of potential benefit) with standard frequentist analysis is very likely to lead to a null effect.

The authors also mentioned that the research team would be blinded for tunneled vs. non-tunneled catheters. This is really not very feasible, as it is easy to identify tunneled vs. non-tunneled catheters. While blinding at the time of analysis can be ensured, data collection would have to be open-label, which is okay, as blinding is not realistic in this type of study.

The authors have also not mentioned any data collection on the success rate of inserting tunneled catheters and complications/costs associated with tunneled catheters compared to standard insertions. It seems like the authors wish to do an intention-to-treat analysis, which is okay. However, they should also do a per-protocol analysis as a sensitivity analysis.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: Yes: Fabrizio D'Ascenzo

Reviewer #2: Yes: Sandeep Tripathi

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To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

TUNNELED PERIPHERALLY INSERTED CENTRAL CATHETER VERSUS NON-TUNNELED AND ITS EFFECTS IN CLINICAL OUTCOMES: A MULTICENTER RANDOMIZED CLINICAL TRIAL PROTOCOL

PONE-D-25-38258R1

Dear Professor Eneida Rejane Rabelo-Silva,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Madhuradhar Chegondi, MD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: all comments have been addressed and authors should be complimented for this good revision again, although synthetic in answers

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: Yes: Fabrizio D'Ascenzo

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