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

NCT ID: NCT07216157

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-15
• Study Completion Date: 2027-03-15

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.

Conditions

CerebroSpinal Fluid (CSF) Leak

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

No Sealant - Standard Multilayer Closure

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.

Group Type: EXPERIMENTAL

Standard multilayer closure without sealant

Intervention Type: PROCEDURE

Patients will undergo standard skull base reconstruction using mucosal flap repositioning and absorbable hemostatics (e.g., Surgicel®, TachoSil®), without application of any fibrin or synthetic sealant. This serves as the control group for comparison with sealant-assisted closures.

Fibrin Glue - Tisseel® Application

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.

Group Type: EXPERIMENTAL

Fibrin sealant application

Intervention Type: DEVICE

Following standard multilayer closure, patients in this group will receive topical application of a fibrin-based biological sealant (Tisseel®). The intervention aims to assess its effectiveness in preventing postoperative cerebrospinal fluid (CSF) leak and promoting mucosal healing after endoscopic endonasal skull base surgery.

Synthetic Sealant - Adherus® Application

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.

Group Type: EXPERIMENTAL

Synthetic polyethylene glycol-based sealant

Intervention Type: DEVICE

After standard multilayer closure, a synthetic two-component sealant (Adherus®, composed of polyethylene glycol and polyethylenimine) will be applied to reinforce the reconstruction site. This group is used to evaluate the efficacy and safety of synthetic sealant in preventing CSF leaks and supporting wound healing.

Interventions

Standard multilayer closure without sealant

Patients will undergo standard skull base reconstruction using mucosal flap repositioning and absorbable hemostatics (e.g., Surgicel®, TachoSil®), without application of any fibrin or synthetic sealant. This serves as the control group for comparison with sealant-assisted closures.

Intervention Type: PROCEDURE

Fibrin sealant application

Following standard multilayer closure, patients in this group will receive topical application of a fibrin-based biological sealant (Tisseel®). The intervention aims to assess its effectiveness in preventing postoperative cerebrospinal fluid (CSF) leak and promoting mucosal healing after endoscopic endonasal skull base surgery.

Intervention Type: DEVICE

Synthetic polyethylene glycol-based sealant

After standard multilayer closure, a synthetic two-component sealant (Adherus®, composed of polyethylene glycol and polyethylenimine) will be applied to reinforce the reconstruction site. This group is used to evaluate the efficacy and safety of synthetic sealant in preventing CSF leaks and supporting wound healing.

Intervention Type: DEVICE

Other Intervention Names

No-sealant technique; Control arm; Tisseel®; Fibrin glue; Human fibrinogen/thrombin sealant; Adherus®; PEI/PEG sealant; Synthetic dural sealant

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maria Sklodowska-Curie National Research Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Wojciech Czyżewski

Wojciech Czyżewski MD, PhD, Neurosurgery Specialist, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Maria Sklodowska-Curie Institute - Oncology Center

Warsaw, , Poland

Site Status: RECRUITING

Countries

Poland

Central Contacts

Wojciech Czyzewski, MD PhD, MD PhD

Role: CONTACT

wojciech.w.czyzewski@gmail.com

+48788599550

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NIO-NS2025

Identifier Type: -

Identifier Source: org_study_id