Efficacy and Safety Evaluation of Absorbable and Moldable Skull Base Support Plates in Extended Endoscopic Endonasal Transsphenoidal Surgery: A Prospective, Randomized, Controlled Study
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 126
- Locations
- 8
- Primary Endpoint
- Incidence of cerebrospinal fluid (CSF) rhinorrhea
Overview
Brief Summary
Primary objective: To evaluate the effect of absorbable and moldable skull base support plates used in extended endoscopic endonasal transsphenoidal surgery on the incidence of cerebrospinal fluid (CSF) rhinorrhea within 1 month after surgery.
Secondary objectives:
- To evaluate the effect of absorbable and moldable skull base support plates used in extended endoscopic endonasal transsphenoidal surgery on the incidence of intracranial infection within 1 months after surgery;
- To evaluate the effect of absorbable and moldable skull base support plates used in extended endoscopic endonasal transsphenoidal surgery on the duration of the surgery and length of postoperative hospital stay;
- To monitor and evaluate the safety of absorbable and moldable skull base support plates, especially the occurrence of nasal complications.
Detailed Description
This is a multicenter, two-arm, open-label, randomized, controlled phase II clinical trial. It plans to enroll patients with sellar region tumors who will undergo extended endoscopic endonasal transsphenoidal approach. The aim is to compare the incidence of CSF rhinorrhea within 1 month after surgery between the combination of standard sellar floor repair + absorbable and moldable skull base support plate repair and the standard sellar floor repair group, and evaluate its safety and efficacy, so as to provide new strategies and basis for clinical treatment.
Statistical Analysis
Analysis Sets:
Full Analysis Set (FAS), Per Protocol Set (PPS), and Safety Set (SS) will be used for statistical analysis.
- Full Analysis Set (FAS): Refers to the set of all subjects who have received the trial after enrollment and have undergone at least one efficacy assessment.
- Safety Set (SS):
Refers to the set of all subjects who have received the trial after enrollment and have undergone at least one safety indicator evaluation.
- Per Protocol Set (PPS): The set of cases in the Full Analysis Set that have completed the trial as specified in the protocol and have no serious violations of the trial protocol.
This is a phase II clinical trial. The sample size of this study will be calculated based on the hypothesis of a 1:1 parallel design sample rate in the two groups. The specific method is to compare the incidence of CSF rhinorrhea (CSF Leakage Rate, CLR) within 1 month after surgery in the experimental group (i.e., standard sellar floor repair + absorbable and moldable skull base support plate repair group) with that in the standard sellar floor repair group. It is assumed that the CLR in the experimental group is 1% (p1=0.01) and that in the standard sellar floor repair group is 15% (p2=0.15). The significance level is set at 0.025 (one-sided test), and the power is 80%. According to literature references and study design, we expect to recruit approximately 56 subjects in each group. Allowing for a 10% loss to follow-up, the sample size will be increased to N = 126 (63 subjects per group).
All statistical analyses will be performed using SAS 9.2 statistical analysis software.
Follow-up Face-to-face oral follow-up will be conducted for patients who return to the hospital for reexamination, and telephone follow-up will be conducted for patients who cannot return to the hospital for reexamination.
Statistical Methods
Data Processing:
Data processing and analysis will be performed using SAS 9.2 statistical analysis software. All continuous variables will be expressed as mean ± standard deviation (Mean ± SD) or median (interquartile range), and categorical variables will be expressed as frequency and percentage.
Analysis of Primary Efficacy Indicators:
Incidence of CSF rhinorrhea (CLR) within 1 month after surgery: Evaluated according to clinical symptoms, imaging, and nasal endoscopy standards. Chi-square test or Fisher's exact test will be used to analyze the CLR of each group.
Analysis of Secondary Efficacy Indicators:
- Incidence of intracranial infection within 1 month after surgery: Inter-group analysis will be performed using chi-square test or Fisher's exact test.
- Utilization rate of autologous fascia, fat, and nasal septum mucosal flaps: Inter-group analysis will be performed using chi-square test or Fisher's exact test.
- Length of duration of the surgery and postoperative hospital stay: Inter-group analysis will be performed using t-test or non-parametric test.
Safety Analysis:
Treatment-related adverse events will be evaluated according to the CTCAE 5.0 standard. The incidence of adverse events in each group will be analyzed using chi-square test or Fisher's exact test, and the frequency and severity of adverse events will be described by category.
Significance Level:
All statistical tests are two-sided tests, and the significance level is set at P < 0.05. P < 0.05 is considered statistically significant.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 80 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Aged 1-80 years, regardless of gender;
- •Diagnosed with sellar region tumors confirmed by clinical symptoms, endocrine examinations, and imaging data;
- •Planned to undergo extended endoscopic endonasal transsphenoidal approach surgery as determined by departmental discussion;
- •Karnofsky Performance Status score ≥ 70, with an expected survival period ≥ 24 months;
- •Laboratory indicators (such as liver and kidney function, blood routine, etc.) within the normal range or controllable range;
- •Sign the informed consent form and are willing to participate in the study.
Exclusion Criteria
- •Patients with other concurrent intracranial tumors or severe brain lesions;
- •Patients scheduled to undergo craniotomy or non-extended endoscopic endonasal transsphenoidal surgery;
- •Patients with uncontrolled severe heart, lung, kidney, or liver diseases;
- •Pregnant or lactating women;
- •Patients who have previously received radiotherapy or chemotherapy;
- •Patients with active nasal infections, inflammation, or severe nasal diseases;
- •Patients with a history of severe allergies to drugs or synthetic materials;
- •Patients with extensive skull base bone destruction evaluated by preoperative imaging, for whom it is estimated that support materials cannot be used during surgery;
- •Patients with mental illness or cognitive impairment who are unable to complete follow-up or understand the purpose of the study.
Arms & Interventions
Standard skull base reconstruction plus the absorbable and moldable skull base support plate
The intervention is performed during the skull base repair phase of the surgery. The sellar floor repair and reconstruction technique used in this study generally follows the multi-layer reconstruction and repair technique widely adopted in the classic endoscopic endonasal transsphenoidal approach :
Assess the intraoperative grade of cerebrospinal fluid (CSF) leakage (Esposito classification).
Obliterate the tumor cavity: After tumor resection, the subarachnoid space and sellar cavity are usually packed with gelatin sponge (or autologous fat in a minority of patients, etc.).
Repair the dura mater: Perform routine inlay repair with an impermeable artificial biomembrane to restore the dural layer.
Trimming, shaping, and placement of the skull base support plate. Covering with mucosa: Cover the outer surface of the support plate with a pedicled or free nasal septal mucosal flap, and pack and stabilize it with gelatin sponge
Intervention: Absorbable and moldable skull base support plate (Device)
Standard skull base reconstruction protocol
No intervention is performed during the skull base repair phase of the surgery. The sellar floor repair and reconstruction technique used in this study generally follows the multi-layer reconstruction and repair technique widely adopted in the classic endoscopic endonasal transsphenoidal approach : Assess the intraoperative grade of cerebrospinal fluid (CSF) leakage (Esposito classification). Obliterate the tumor cavity: After tumor resection, the subarachnoid space and sellar cavity are usually packed with gelatin sponge (or autologous fat in a minority of patients, etc.). Repair the dura mater: Perform routine inlay repair with an impermeable artificial biomembrane to restore the dural layer. Cover with mucosa: Cover the outer surface of the dural layer with a pedicled or free nasal septal mucosal flap, and pack and stabilize it with gelatin sponge
Outcomes
Primary Outcomes
Incidence of cerebrospinal fluid (CSF) rhinorrhea
Time Frame: Within 1 month postoperatively
Confirmed by combining clinical symptoms, imaging examinations, and nasal endoscopy, including but not limited to the following indicators: Clinical symptoms: persistent high fever (maximum temperature \> 38.5 °C for more than 3 days), nausea and vomiting, decreased consciousness, positive meningeal irritation signs, etc.; Imaging examinations: CT or MRI showing fluid accumulation in the paranasal sinuses, intracranial pneumocephalus, etc.; Nasal endoscopy demonstrating persistent cerebrospinal fluid leakage from the sellar floor wound.
Secondary Outcomes
- Incidence of intracranial infection(Within 1 month postoperatively)