NoSeal Trial: Comparing Sealants Versus No Sealant for Preventing CSF Leak After Endonasal Skull Base Surgery

Maria Sklodowska-Curie National Research Institute of Oncology

Status: Enrolling

Conditions: CerebroSpinal Fluid (CSF) Leak

Treatments: Procedure: Standard multilayer closure without sealant; Device: Fibrin sealant application; Device: Synthetic polyethylene glycol-based sealant

Study type: Interventional

Funder types: Other

Identifiers

NCT07216157

NIO-NS2025

Details and patient eligibility

About

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.

Full 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.

Enrollment: 225 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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225 participants in 3 patient groups

No Sealant - Standard Multilayer Closure

Experimental group

Description:

Patients in this arm will receive standard multilayer closure without the use of any sealant. Closure will involve mucosal flap repositioning and hemostatic agents (e.g., Surgicel®, TachoSil®), in accordance with standard endoscopic skull base reconstruction techniques.

Treatment:

Procedure: Standard multilayer closure without sealant

Fibrin Glue - Tisseel® Application

Experimental group

Description:

Patients will undergo standard multilayer closure followed by application of fibrin sealant (Tisseel®). This arm evaluates the effect of biologic tissue glue in preventing postoperative CSF leaks and promoting wound healing following endonasal skull base surgery.

Treatment:

Device: Fibrin sealant application

Synthetic Sealant - Adherus® Application

Experimental group

Description:

This arm involves standard multilayer closure followed by the application of a two-component synthetic polyethylene glycol-based sealant (Adherus®). The objective is to evaluate the synthetic agent's efficacy and cost-effectiveness in reducing postoperative CSF leaks.

Treatment:

Device: Synthetic polyethylene glycol-based sealant