Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial

Trials (2023) 24:488 Coucke et al. Trials https://doi.org/10.1186/s13063-023-07492-w Open Access STUDY PROTOCOL Leukocyte‑ and platelet‑rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel‑group, single‑blinded randomized controlled non‑inferiority trial Birgit Coucke1,2* , Anaïs Van Hoylandt3, Mark Jorissen4,5, Jeroen Meulemans4,6, Thomas Decramer1,3, Johannes van Loon1,3, Vincent Vander Poorten4,6, Tom Theys1,3† and Laura Van Gerven2,4,5† Abstract Background Recent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETArelated skull base reconstruction reinforcement. Methods/design This multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed. Discussion With this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants. Trial registration ClinicalTrials.gov NCT03910374. Registered on 10 April 2019. Keywords Cerebrospinal fluid leakage, Endoscopic endonasal transsphenoidal approach, Dura, Regenerative medicine, Skull base, Prevention, Leukocyte- and platelet-rich fibrin † Tom Theys and Laura Van Gerven shared the last authorship. *Correspondence: Birgit Coucke Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Coucke et al. Trials (2023) 24:488 Administrative information We used the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2013) checklist when writing our report [1]. The numbers in curly brackets in this protocol correspond to the SPIRIT checklist item numbers. Title {1} Leukocyte- and platelet-rich fibrin endoscopic endonasal skull base reconstruction: a multicenter prospective, randomized controlled trial. Trial registration {2} ClinicalTrials.gov (ID: NCT03910374) https://clinicaltrials.gov/ct2/show/NCT03 910374 KU/UZ Leuven: S61636 Protocol version {3} V5 dd 9-11-2021 Funding {4} FWO TBM grant T003018N The design of the study has been reviewed by FWO, but FWO has no role in data collection, analysis, and interpretation of data nor in writing the manuscript. Author details {5a} Otorhinolaryngology-Head and Neck Surgery, UZ Leuven, Leuven, Belgium Neurosurgery, UZ Leuven, Leuven, Belgium Name and contact informa- UZ Leuven tion for the trial sponsor {5b} Herestraat 49, 3000 Leuven, Belgium +32 16 33 22 11 Role of sponsor {5c} The sponsor has no role in the design of the study, study conduct, collection of data, analysis nor in writing of trial manuscripts. Date and version identifier {3} Date Version 16-5-2018 Original (v1) 30-8-2018 Amendment no.1: Sample size recalculation (v3) 5-2-2020 Amendment no.2: Addition of ICF translated in English 17-3-2020 Digital follow-up possible (COVID-19 restrictions) 8-5-2020 Amendment no. 3: Addition of ICF translated in French 30-3-2021 Amendment no. 4: Addition of quality control measures (v4) 30-6-2022 Amendment no. 5: Addition of a third participating center: UZ Gent (v5) Background and rationale {6a} The endoscopic endonasal transsphenoidal approach (EETA) to the skull base is a minimally invasive surgical technique that is used to treat a wide range of conditions affecting the skull base, such as pituitary tumors, suprasellar tumors and other diseases of the skull base. EETA is performed through the nasal cavity, without the need for an open craniotomy or facial incision, which leads to a faster recovery, reduced postoperative pain, and a lower risk of complications. Page 2 of 11 However, the nasal cavity is a delicate and complex area that requires precise surgical techniques and can be susceptible to bleeding and inflammation. Additionally, recent advancements in endoscopic endonasal approaches (EEA) for skull base lesions have resulted in a significant increase in the extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to improve healing and prevent reconstruction failure. One major complication of EETA is postoperative cerebrospinal fluid (CSF) leakage. Our recently published systematic review, summarizing data from 113 studies, showed an average postoperative CSF leakage rate of 4.1% in endoscopic transsphenoidal surgeries [2]. A well-known risk factor for postoperative CSF leak is the presence of intraoperative leakage, in case of malignancy or, in cases where a thinned arachnoid herniates into the sella. As the pituitary is located in the diaphragma sellae, a double fold of the du (...truncated)