CerebroSpinal Fluid (CSF) LeakNoSealNCT07216157
NoSeal Trial: Comparing Sealants Versus No Sealant for Preventing CSF Leak After Endonasal Skull Base Surgery
A study testing Standard multilayer closure without sealant, Fibrin sealant application and Synthetic polyethylene glycol-based sealant in people with CerebroSpinal Fluid (CSF) Leak, run by Maria Sklodowska-Curie National Research Institute of Oncology at 1 site in Poland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CerebroSpinal Fluid (CSF) Leak
- What is being tested?
- Standard multilayer closure without sealant, Fibrin sealant application and Synthetic polyethylene glycol-based sealant
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 1 sitePoland
- Study dates
- 15 Aug 2025to 15 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
Maria Sklodowska-Curie Institute - Oncology Center
Warsaw
About this study
Official title: The NoSeal Trial - Nasal Outcome Study Evaluating Artificial Leak-Sealing: A Prospective, Randomized, Controlled, Single-Blinded, Single-Center Clinical Trial Comparing Fibrin Glue (Tisseel®) and a Two-Component Synthetic Polymer Sealant (PEI/PEG, Adherus®) Versus No Sealant for the Prevention of Cerebrospinal Fluid Leak and Promotion of Wound Healing Following Endonasal Skull Base Surgery, Designed in Accordance With the SPIRIT 2025 Guidelines
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.
Read the 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
- Being tested
- Standard multilayer closure without sealant, Fibrin sealant application, Synthetic polyethylene glycol-based sealant
- Keywords
- csf, pituitary adenoma, csf leak, sealant
- Medical subject headings
- Pituitary Neoplasms, Cerebrospinal Fluid Otorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard multilayer closure without sealantProcedure or surgery
Also called No-sealant technique, Control arm
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 sealant applicationDevice
Also called Tisseel®, Fibrin glue, Human fibrinogen/thrombin sealant
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 polyethylene glycol-based sealantDevice
Also called Adherus®, PEI/PEG sealant, Synthetic dural 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.
| Study group | Role | What they receive |
|---|---|---|
| No Sealant - Standard Multilayer Closure | Experimental | 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. Receives: Procedure: Standard multilayer closure without sealant |
| Fibrin Glue - Tisseel® Application | Experimental | 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. Receives: Device: Fibrin sealant application |
| Synthetic Sealant - Adherus® Application | Experimental | 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. Receives: Device: Synthetic polyethylene glycol-based sealant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of postoperative cerebrospinal fluid (CSF) leak within 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.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2025
- Study start15 Aug 2025
- Primary completion30 Dec 2026 (estimated)
- Study completion15 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CerebroSpinal Fluid (CSF) LeakStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maria Sklodowska-Curie National Research Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wojciech Czyżewski, Maria Sklodowska-Curie National Research Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07216157
- Sponsor's protocol ID
- NIO-NS2025
- Acronym
- NoSeal
- Status last verified
- Jul 2025
- First submitted
- 28 Sep 2025
- Last updated
- 14 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified individual participant data (IPD) to be shared will include: Demographics (age, sex) Preoperative imaging risk features Intraoperative findings (CSF leak grade, reconstruction technique) Treatment allocation (sealant type or no sealant) Primary and secondary outcomes (e.g., CSF leak occurrence, mucosal healing scores, complication rates, SNOT-22 and VAS scores) Follow-up data at 4 and 12 weeks Reoperation status Adverse events
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NoSeal Trial - Nasal Outcome Study Evaluating Artificial Leak-Sealing: A Prospective, Randomized, Controlled, Single-Blinded, Single-Center Clinical Trial Comparing Fibrin Glue (Tisseel®) and a Two-Component Synthetic Polymer Sealant (PEI/PEG, Adherus®) Versus No Sealant for the Prevention of Cerebrospinal Fluid Leak and Promotion of Wound Healing Following Endonasal Skull Base Surgery, Designed in Accordance With the SPIRIT 2025 Guidelines
- ClinicalTrials.gov ID
- NCT07216157
- Acronym / sponsor ID
- NoSeal / NIO-NS2025
- Conditions
- CerebroSpinal Fluid (CSF) Leak
- Keywords
- csf, pituitary adenoma, csf leak, sealant
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- Maria Sklodowska-Curie National Research Institute of OncologyUniversity, hospital or other
- Study start
- 15 Aug 2025 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 15 Mar 2027 (estimated)
- First posted
- 14 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| No Sealant - Standard Multilayer Closure | Experimental | Procedure: Standard multilayer closure without sealantPatients 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. |
| Fibrin Glue - Tisseel® Application | Experimental | Device: Fibrin sealant applicationPatients 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. |
| Synthetic Sealant - Adherus® Application | Experimental | Device: Synthetic polyethylene glycol-based sealantThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard multilayer closure without sealantAlso: No-sealant technique, Control armPatients 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. | Procedure or surgery | No Sealant - Standard Multilayer Closure |
| Fibrin sealant applicationAlso: Tisseel®, Fibrin glue, Human fibrinogen/thrombin sealantFollowing 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. | Device | Fibrin Glue - Tisseel® Application |
| Synthetic polyethylene glycol-based sealantAlso: Adherus®, PEI/PEG sealant, Synthetic dural sealantAfter 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. | Device | Synthetic Sealant - Adherus® Application |
Primary outcome
Incidence of postoperative cerebrospinal fluid (CSF) leak within 90 days
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2025.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) to be shared will include: Demographics (age, sex) Preoperative imaging risk features Intraoperative findings (CSF leak grade, reconstruction technique) Treatment allocation (sealant type or no sealant) Primary and secondary outcomes (e.g., CSF leak occurrence, mucosal healing scores, complication rates, SNOT-22 and VAS scores) Follow-up data at 4 and 12 weeks Reoperation status Adverse events
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard multilayer closure without sealant, Fibrin sealant application and Synthetic polyethylene glycol-based sealant in people with CerebroSpinal Fluid (CSF) Leak, run by Maria Sklodowska-Curie National Research Institute of Oncology at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wojciech Czyzewski, MD PhD, MD PhD (+48788599550, wojciech.w.czyzewski@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of postoperative cerebrospinal fluid (CSF) leak within 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025.