Clinical trial NCT04572568: Registry of Multimodality Treatment for Brain Arteriovenous Malformation in Mainland China
Official title: Registry of Multimodality Treatment for Brain Arteriovenous Malformation in Mainland China
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Brain Arteriovenous Malformation
Keywords: Brain Arteriovenous Malformation
multi-disciplinary treatment
embolization
stereotactic radiosurgery
microsurgical resection
hybrid surgery
conservative/medical treatment
hemodynamic
outcomes
subsequent hemorrhage
obliteration
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Neurosurgical Institute
name: Peking University International Hospital
name: West China Hospital
name: First Affiliated Hospital of Harbin Medical University
name: Sichuan Provincial People's Hospital
name: The First Hospital of Jilin University
name: Shanxi Provincial People's Hospital
name: The Second Hospital of Shandong University
name: The First Affiliated Hospital of Zhengzhou University
name: First Affiliated Hospital of Xinjiang Medical University
name: The General Hospital of Central Theater Command
name: The Affiliated Hospital Of Guizhou Medical University
name: First Affiliated Hospital of Guangxi Medical University
name: Tianjin Medical University Second Hospital
name: The First Affiliated Hospital of Shanxi Medical University
name: Shengjing Hospital
name: Second Affiliated Hospital of Guangzhou Medical University
name: Hainan People's Hospital
name: The Second Affiliated Hospital of Kunming Medical University
name: The Affiliated Hospital of Qingdao University
name: Second Xiangya Hospital of Central South University
name: Second Affiliated Hospital of Soochow University
name: General Hospital of Ningxia Medical University
name: Lanzhou University Second Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: First Affiliated Hospital of Zhejiang University
name: Qilu Hospital of Shandong University
name: Jining Medical University
name: First Affiliated Hospital of Chongqing Medical University
name: First Affiliated Hospital of Fujian Medical University
name: Shandong Provincial Hospital
name: The Affiliated Hospital of Xuzhou Medical University
name: Henan Provincial People's Hospital
name: Binzhou Medical University
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
First posted: 2020-10-01
Enrollment: 2000
Sex: ALL
Minimum age (years): 1
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with the diagnosis of AVM was confirmed with digital subtraction angiography (DSA) and/or magnetic resonance imaging(MRI).

Brief summary: This study is a multi-center, prospective, registry study. This research was supported by the National Key Research and Development Program. They were divided into experimental group and control group according to whether the treatment plan was formulated by a multidisciplinary team. Patients of experimental group is strictly in accordance with standardized multi-disciplinary treatment protocols and meet the following criteria: 1. A multi-disciplinary conference discussion; 2. Detailed preoperative evaluation based on CT, MRI, fMRI and DSA. 3. Treatment modalities meet the following treatment criteria（craniotomy, embolization and stereotactic radiosurgery）. The control group was patients who had not been treated according to a multi-disciplinary treatment protocol.

Patient baseline data, AVM angioarchitectural features, imaging DICOM data, surgical information, and follow-up information were registered. All patients were evaluated for neurofunction at baseline, 3 months, 12 months, and 3 years after treatment. Main observation endpoints: 1. Modified Rankin Scale; 2. Obliteration rate; 3. Subsequent hemorrhage; 4. Complication rate (such as morbidity rate, new-onset neurological dysfunction, and radiation-related complications). Secondary observation endpoint: improvement of clinical symptoms (epilepsy, headache, neurological dysfunction) at 3 months, 12 months, and 3 years after treatment.

Detailed description: This study is a multi-center, prospective registry study led by Beijing Tiantan Hospital, and a number of comprehensive hospitals in mainland China, aiming to uncover the long-term outcomes of AVM in Real-World in China and to discover a standardized diagnosis and treatment process for the comprehensive treatment of brain AVMs. This study is an observational study that will last for 20 years. All patients were enrolled prospectively, and the study will not influence the choice of treatment modalities.

The study cohort of this study was AVM patients aged 1-80 years. The inclusion criteria were as follows: 1. The diagnosis of AVM was confirmed with digital subtraction angiography (DSA) and/or magnetic resonance imaging(MRI); 2.Patients with complete clinical and imaging data; 3. Patient or patient's legal representative agreed to collection of information for this study and signed informed consent. The exclusion criteria were as follows: 1. Received other treatment (surgery, embolization or SRS)before inclusion; 2. Expected survival time is less than 6 months; 3. Spinal AVMs; 4. Patients missing critical baseline and imaging data.

Patients will be divided into two groups: experimental group and control group. Experimental group: Patients who had received a multidisciplinary assessment to develop a treatment plan were included in the experimental group. The details were as follows: Ruptured AVMs: 1. AVMs not involved vital eloquent areas, or more than 5 mm away from functional fiber bundles, microsurgery or hybrid surgery can be performed; 2. Targeted embolization for hemorrhagic predictors could be considered as a monotherapy; embolization can be used as an adjunctive strategy to reduce flow or volume before microsurgery or stereotactic radiosurgery (SRS); 3. SRS for patients with a volume less than 10ml and not in the acute phase(\< 3months) of hemorrhage. Volume-stage or dose-stage can be used for giant AVMs involving important eloquent areas; 4.Conservation can be used for AVMs that are prone to severe disability due to intervention. Unruptured AVMs: Interventions are recommended if unruptured AVMs are assessed as being at high rupture risk, or have refractory epilepsy or acceptable postoperative neurological deficits, otherwise conservative treatment is recommended. The choice of intervention strategy was the same as for ruptured AVM. Control group: Patients who had not received a multidisciplinary assessment to develop a treatment plan were included in the control group. It should be noted that the multidisciplinary team for AVM was formed in June 2018, so the prospective AVM cohort from August 2011 to June 2018 and the AVM cohort after June 2018 without comprehensive evaluation of treatment regimens by the multidisciplinary team served as the control group.

An electronic data capture system (EDC) was developed and used for data collection. All the clinical baseline data and imaging data were stored through a cloud server to facilitate the input work at different locations and at different times. Follow-up was conducted at the first 3-6 months and annually after surgery by clinical visit and telephone interview. The evaluation of mRS score was conducted by neurosurgeons who have at least 5 years' experience of clinical practice and all the images were interpreted by at least 2 radiologists independently who are with at least 5 years of clinical experience in radiology center of our institute. Researchers who performed follow-up assessments were blinded to treatment modalities.

The primary outcomes were as follows: modified Rankin Scale, obliteration rate, subsequent hemorrhage, complication rate (such as morbidity rate, new-onset neurological dysfunction, and radiation-related complications) at 3 months, 12 months, and 3 years after treatment. The secondary outcomes were as follows: improvement of clinical symptoms (epilepsy, headache, neurological dysfunction) at 3 months, 12 months, and 3 years after treatment.

Through the final follow-up data, we could compare the short-term outcomes and long-term outcomes between experimental and control group. In addition, intra-group comparisons can be made among subgroups of different intervention strategies to explore the best individualized treatment strategies for different AVM patients.

Treatment criteria for craniotomy: 1. For patients with a history of rupture and bleeding: a. If the lesion is not located in the deep functional area, surgical treatment is recommended; b. If the lesion is multi-system blood supply or high blood flow, the volume is large, and with a deep blood supply, hybrid surgery (embolization + resection) can be performed; c. If the lesion is located in the deep functional area, craniotomy is not recommended. 2. For patients with unruptured hemorrhage: a. If the lesion is not located in the deep brain tissue, and is not located in an important functional area or the fiber bundle is more than 5mm away from the lesion, then surgery or combined surgery can be performed; b. If the lesion is located in the deep brain tissue, important functional areas or fiber bundles are less than 5mm away from the lesion, craniotomy is not recommended; c. If the lesion does not have the above characteristics, surgical resection alone can be performed.

Interventional embolization treatment standards: 1. Ruptured bAVM should be actively treated. If there is no need for craniotomy to clear the hematoma in the acute phase, DSA should be performed 2-6 weeks after hemorrhage, and individualized treatment plans should be developed and actively treated. 2. Unruptured bAVM, if there are bleeding-related risk factors (aneurysm or high-flow fistula), relevant risk factors should be actively treated; When stereotactic radiation is planned, when craniotomy or SRS was planned, preoperative embolization for flow reduction or volume reduction is recommended; 3. Unruptured bAVM, without the above risk factors, conservative treatment was suggested if symptoms could be well controlled.

Stereotactic radiosurgery standard treatment: 1. No history of bleeding: Patients with no indications for craniotomy and with appropriate volume for radiosurgery, and poor symptom controlled. Pre-treatment imaging assessment DSA (required) and enhanced MRI was required to clarify the structure of the malformation; 2. There is a history of bleeding: the period between bleeding time and the time of consultation is less than 3 months, it is recommended to wait head-enhanced MRI and DSA were performed after the hemorrhage was absorbed (3 months) to confirm the vascular architecture. 3.Volume-stage or dose-stage can be used for giant AVMs involving important eloquent areas.

Conservation standard treatment: 1. Ruptured AVMs: Patients prone to severe disability due to intervention; 2. Unruptured AVMs: Patients were assessed as having a low rupture risk, or without refractory epilepsy or with a high risk of postoperative neurological deficits.

Eligibility criteria: Inclusion Criteria:

1. The diagnosis of AVM was confirmed with digital subtraction angiography (DSA) and/or magnetic resonance imaging(MRI).
2. Patients with complete clinical and imaging data.
3. Patient or patient's legal representative agreed to collection of information for this study and signed informed consent.

Exclusion Criteria:

1. Received other treatment (surgery, embolization or SRS)before inclusion;
2. Expected survival time is less than 6 months;
3. Spinal AVMs;
4. Patients missing critical baseline and imaging data.

Primary outcomes:
measure: modified Rankin Scale
timeFrame: 3 months, 1 year, and 3 years after treatment
measure: obliteration rate
timeFrame: 3 months, 1 year, and 3 years after treatment
measure: subsequent hemorrhage
timeFrame: 3 months, 1 year, and 3 years after treatment
measure: complication rate
timeFrame: 3 months, 1 year, and 3 years after treatment
Secondary outcomes:
measure: Improvement of epilepsy
timeFrame: 3 months, 1 year, and 3 years after treatment
measure: Improvement of headache
timeFrame: 3 months, 1 year, and 3 years after treatment
measure: Improvement of neurological dysfunction
timeFrame: 3 months, 1 year, and 3 years after treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital medical university affiliated Beijing Tiantan hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Wang Shuo, MD
role: STUDY_CHAIR
affiliation: Beijing Neurosurgical Institute
name: Li Youxiang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Neurosurgical Institute
name: Liu Ali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Neurosurgical Institute
name: Zhao Yuanli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Neurosurgical Institute
name: Chen Xiaolin, MD
role: PRINCIPAL_INVESTIGATOR
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