NoSeal Trial: Comparing Sealants Versus No Sealant for Preventing CSF Leak After Endonasal Skull Base Surgery
- Conditions
- CerebroSpinal Fluid (CSF) Leak
- Registration Number
- NCT07216157
- Brief Summary
Postoperative cerebrospinal fluid (CSF) leak is a significant complication of endoscopic endonasal approaches (EEA) to the skull base. The use of tissue sealants such as fibrin glue (Tisseel) or synthetic agents (PEI/PEG) is widespread in surgical practice, however, recent high-quality evidence challenges their clinical benefit and cost-effectiveness. This study aims to investigate whether the routine use of sealants in patient with peri-operatively assessed low CSF leak risk, significantly improves outcomes over no sealant use, to guide more cost- effective, evidence-based closure strategies. To the best of our knowledge, the present study is the first randomized clinical trial to evaluate the necessity and comparative effectiveness of fibrin and synthetic sealants versus no sealant in preventing postoperative CSF leaks following endoscopic endonasal surgery in low-post operative CSF leak risk patients.
- Detailed Description
Introduction Postoperative cerebrospinal fluid (CSF) leak is a significant complication of endoscopic endonasal approaches (EEA) to the skull base. The use of tissue sealants such as fibrin glue (Tisseel) or synthetic agents (PEI/PEG) is widespread in surgical practice, however, recent high-quality evidence challenges their clinical benefit and cost-effectiveness. This study aims to investigate whether the routine use of sealants in patient with peri-operatively assessed low CSF leak risk, significantly improves outcomes over no sealant use, to guide more cost- effective, evidence-based closure strategies. To the best of our knowledge, the present study is the first randomized clinical trial to evaluate the necessity and comparative effectiveness of fibrin and synthetic sealants versus no sealant in preventing postoperative CSF leaks following endoscopic endonasal surgery in low-post operative CSF leak risk patients. Materials and Methods This is a prospective, randomized, controlled, single-center clinical trial conducted at the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland.
Adult patients scheduled for endoscopic endonasal surgery (EES) will first undergo screening based on medical history and detailed radiological evaluation. Those who meet all predefined inclusion and exclusion criteria will be enrolled and randomized preoperatively using a computer-generated allocation sequence into one of three treatment arms: (1) no sealant (standard multilayer closure), (2) fibrin glue application (Tisseel®), or (3) synthetic polyethylene glycol-based sealant (Adherus®). Following randomization, surgery will be performed in accordance with the assigned intervention. The primary endpoint is the incidence of postoperative cerebrospinal fluid (CSF) leak within 3 months. Secondary outcomes include endoscopic evaluation of mucosal healing at 6 weeks and 3 months, postoperative complication rates (e.g., meningitis, pneumocephalus), reoperation rate, patient-reported quality of life, and a cost-effectiveness analysis comparing sealant use to standard closure. The study is designed and will be reported in accordance with the SPIRIT 2025 (Standard Protocol Items: Recommendations for Interventional Trials) guidelines to ensure methodological transparency and reproducibility. Results Initial enrollment includes a target of 225 patients (75 per arm). Interim data analysis focuses on early healing parameters, safety profiles, and cost metrics. Hypothesis testing will determine if either sealant significantly reduces CSF leak rates compared to no sealant and whether the marginal benefit justifies routine use in all patients. Exploratory endpoints include biomaterial handling characteristics and surgeon-reported usability. Conclusion The NoSeal Trial addresses a critical gap in evidence regarding the necessity and comparative performance of sealants in skull base reconstruction. By evaluating both clinical outcomes and economic impact, the study seeks to optimize surgical protocols and improve the safety and efficiency of endonasal neurosurgical procedures.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 225
- Age ≥ 18 years
- Scheduled for endoscopic endonasal surgery involving standard skull base reconstruction
- Informed written consent obtained prior to enrollment
- Hemodynamic and electrolyte stability before surgery
- Procedure expected to be completed without use of high-flow intraoperative CSF diversion techniques
- Revision surgery or extended endoscopic approaches requiring complex reconstruction (e.g., clival or cribriform defects)
- Tumors requiring complex sella reconstruction from the start
- Preoperative hydrocephalus
- Known allergy to fibrin-based or synthetic sealant components
- Active sinus infection or systemic inflammatory disease
- Prior radiotherapy to the sellar or parasellar region
- Uncontrolled diabetes mellitus (HbA1c > 7.0%)
- Participation in another interventional trial that may influence wound healing or CSF assessment
- Radiologic signs of chronic intracranial hypertension or hypotension
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Incidence of postoperative cerebrospinal fluid (CSF) leak within 90 days 90 days Postoperative CSF leak will be assessed clinically and endoscopically at multiple time points (Day 2, Day 30, Day 90). A leak will be defined as visible or symptomatic leakage of cerebrospinal fluid from the nasal cavity, confirmed by clinical exam and/or imaging when necessary. Assessment will be blinded and recorded using standardized diagnostic criteria.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Maria Sklodowska-Curie Institute - Oncology Center
🇵🇱Warsaw, Poland
Maria Sklodowska-Curie Institute - Oncology Center🇵🇱Warsaw, Poland