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Effects of adding adjunctive hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers: a protocol for a systematic review with meta-analysis and trial sequential analysis
  1. Julie Vinkel1,
  2. Niels Frederich Rose Holm1,
  3. Janus C Jakobsen2,3,4,5,
  4. Ole Hyldegaard1
  1. 1Department of Anaesthesia, Centre of Head and Orthopaedics, Copenhagen University Hospital, Copenhagen, Rigshospitalet, Denmark
  2. 2The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Rigshospitalet, Denmark
  3. 3Department of Cardiology, Holbaek Sygehus, Holbaek, Sjaelland, Denmark
  4. 4Department of Regional Health Research, The Faculty of Heath Sciences University of Southern Denmark, Odense, Denmark
  5. 5Department of Cardiology, Holbæk Hospital, Holbaek, Denmark
  1. Correspondence to Dr Julie Vinkel; julie.vinkel.clausen{at}


Introduction Diabetic foot ulcer represents a major health problem globally. Preliminary studies have indicated that systemic treatment of diabetic foot ulcer patients with hyperbaric oxygen therapy have beneficial effects on wound healing, risk of amputation, glycaemic control, atherosclerosis, inflammatory markers and other clinical and laboratory parameters. This protocol for a systematic review aims at identifying the beneficial and harmful effects of adding hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers.

Methods and analysis This protocol was performed following the recommendations of the Cochrane Collaboration and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the effects of hyperbaric oxygen therapy in the treatment of diabetic foot ulcer versus any control group with any intervention defined as standard wound care or similar, together with sham interventions. Our primary outcome will be: all-cause mortality, serious adverse events and quality of life. Our secondary outcomes will be: healing of index wound, major amputation and wound infection. Any eligible trial will be assessed and classified as either high risk of bias or low risk of bias, and our conclusions will be based on trials with low risk of bias. The analyses of the extracted data will be performed using Review Manager 5 and Trial Sequential Analysis. For both our primary and secondary outcomes, we will create a ‘Summary of Findings’ table and use GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment to assess the quality of the evidence.

Ethics and dissemination We use publicly accessible documents as evidence, there is no participant involvement at an individual level and an institutional ethics approval is not required. The results of the review will be sought published in a peer-reviewed journals, also in the event of insignificant results or null results, and thereby it will be disseminated to clinicians and public available.

PROSPERO registration number CRD42019139256.

  • diabetic foot
  • trial sequential analysis
  • meta-analysis
  • systematic review
  • hyperbaric oxygen therapy

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Contributors JV drafted the protocol. NFRH, JCJ and OH amended the protocol. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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