Clinical trial NCT04198181: The Effectiveness and Safety of Resective Epilepsy Surgery for TRE
Official title: Clinical Evaluation of the Effectiveness and Safety of Resective Epilepsy Surgery for Tuberous Sclerosis Complex Related Epilepsy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Tuberous Sclerosis Complex
Epilepsy
Keywords: epilepsy
tuberous sclerosis complex
resective epilepsy surgery
Lead sponsor: Beijing Children's Hospital
Sponsor class: OTHER
Collaborators: name: Shenzhen Children's Hospital
name: Capital Medical University
name: Peking University People's Hospital
name: Guangdong 999 Brain Hospital
name: Xinqiao Hospital, Amry Medical University
name: Shandong Provincial Hospital
name: West China Hospital
name: Henan Provincial People's Hospital
name: Shanghai Children's Hospital
name: First Medical Center, PLA General Hospital
name: Fourth Medical Center, PLA General Hospital
name: The First Affiliated Hospital of University of Science and Technology of China
name: Ruijin Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: The Second Hospital of Hebei Medical University
name: The First Affiliated Hospital of Shanxi Medical University
name: Xuanwu Hospital, Beijing
name: The First Hospital of Jilin University
name: Xiangya Hospital of Central South University
name: Beijing Sanbo Brain Hospital
name: Nanjing Medical University
First posted: 2019-12-13
Enrollment: 200
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from participating medical institutions

Brief summary: A prospective cohort studies to identify clinical seizure control, cognitive changes, and safety in resective epilepsy surgery in patients with TSC-related drug-resistant epilepsy.

Detailed description: Two hundred candidates are recruited and assigned to the control and surgery groups with 100 cases in each group, respectively. All patients will accept first-stage pre-enrollment evaluations and patients in surgery group will accept second-stage invasive evaluation.

All patients will be advised to visit the hospitals for examination each year after enrollment. Seizure outcomes will be assessed with reference to patients' seizure diaries and caregivers' oral statements by both neurosurgeons and neurologists.

All adverse effects will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (2017).

Statistical analyses were conducted using SPSS (version 26.0, IBM, USA), Stata (version 16.0, Stata Corp LLC, USA), and R (version 4.3.3, R Foundation for Statistical Computing, Austria). Outcomes were presented according to data type as percentages, mean ± standard deviation, or median (interquartile range, IQR).

Multiple imputation was employed to address missing data for IQ and QOL at enrollment and the 2-year follow-up. A sensitivity analysis was conducted to assess the robustness of the multiple imputation results. The "mi impute regress" statement in Stata facilitated the multiple imputations. 20 T-tests were utilized for comparing continuous variables, with results reported as mean ± standard deviation. The Mann-Whitney U test was applied for non-normally distributed continuous variables, presenting results as median values and IQRs. Chi-square and Fisher's exact tests were used for univariate analyses. A significance level of p \< 0.05 was established.

To account for differences in covariates between the surgery and medicine groups, propensity score matching (PSM) was performed. Based on PSM, Kaplan-Meier curves and the log-rank test were utilized to analyze time-to-seizure recurrence differences between the surgery and medicine groups. Additionally, multivariable Cox proportional hazards regression was applied to predict risk factors for postoperative seizure recurrence within a 51-month follow-up period after PSM.

Eligibility criteria: Inclusion Criteria:

* 2 years old and above, no gender restriction, TSC gene monitoring with or without abnormality
* Diagnosis of tuberous sclerosis- related drug-resistant epilepsy
* Epilepsy course for more than 1 year
* Patients who have taken 3 or more reasonable choices with appropriate and tolerable antiepileptic drugs (excluding mTOR inhibitors and traditional Chinese medicine and prescriptions) had seizures more than 12 times in the 3 months before enrollment
* The family members agreed to enroll and signed the informed consent.

Exclusion Criteria：

* Obvious renal angiomyolipoma, pulmonary lymphoma leiomyomatosis, and subventricular giant cell astrocytoma
* Abnormal heart, lung, liver, and kidney functions and coagulation function
* Preoperative evaluation, it is considered that no surgical treatment is needed
* The patient received other craniocerebral surgical treatment within 1 year during the follow-up period

Primary outcomes:
measure: % of patients with ILAE grading
timeFrame: 3 years
Secondary outcomes:
measure: IQ
timeFrame: 3 years
measure: Quality of Life: QOLIE-31
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital
state: Beijing
Study officials:
References: