A Multicenter, RAndomlzed, coNtrolled, umBrella Trial fOr Minimally Invasive Neurosurgery With Al-assisted Robotic guidanCe for Hemorrhagic Stroke: Large Basal Ganglia Hemorrhage (RAINBOW-LBH)

This substudy is a prospective, multicenter, parallel-controlled, randomized controlled trial designed to evaluate whether robot-assisted endoscopic evacuation of large basal ganglia hematomas can improve patient outcomes compared with traditional surgical approaches such as small craniotomy or large-bone-flap intracranial hematoma evacuation.

Study Overview

• Status: Recruiting
• Conditions: Hematoma Brain; Large Basal Ganglia Hemorrhage
• Intervention / Treatment: Procedure: Robot-Assisted Endoscopic Minimally Invasive Surgery; Procedure: Traditional Surgical Approaches

Detailed Description

This substudy adopts an open-label design, while outcome assessment is performed in a blinded manner. The primary outcome is the modified Rankin Scale (mRS) at 6 months. Outcomes at 30 days, 90 days, and 6 months will also be assessed. Follow-up will be conducted at baseline; 24 hours after surgery/ 30 hours after randomization; 48 hours; Day 3; Day 14 or at discharge; Day 30; Day 90; and Month 6. During follow-up, data will be collected on mortality, survival, ambulation status, living situation, modified Rankin Scale, EQ-5D-5L, Fatigue Severity Scale, AD8, Lawton-Brody Instrumental Activities of Daily Living Scale, National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale, laboratory tests, and neuroimaging findings.

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chun-Hua Hang, PhD; Phone Number: 025-83106666; Email: hang_neurosurgery@163.com

Study Locations

• China
  • Nanjing, China
    • Recruiting
    • The Affiliated Drum Tower Hospital of Nanjing University Medical School
    • Contact: Chunhua Hang; Phone Number: 025-83106666; Email: hang_neurosurgery@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years at randomization;
2. Diagnosed with hypertensive basal ganglia hemorrhage via imaging (CT, CTA, etc.);
3. Hematoma volume ≥30 mL prior to randomization;
4. Glasgow Coma Scale (GCS) score ≥ 5;
5. Available for surgery within 72 hours after onset;
6. Modified Rankin Scale (mRS) score ≤ 1 prior to this hemorrhage;
7. Informed consent obtained in accordance with national laws, regulations, and applicable ethics committee requirements.

Exclusion Criteria:

1. Hematoma involving the thalamus (volume >5 mL or diameter >2 cm), midbrain, or ventricles (Graeb score ≥3), or other locations;
2. Radiologically confirmed cerebral vascular abnormalities including ruptured aneurysms, arteriovenous malformations (AVMs), or Moyamoya disease; hemorrhagic transformation of ischemic infarcts; or recent (within 1 year) recurrence of intracerebral hemorrhage;
3. Signs of impending herniation such as midline shift exceeding 1 cm or ipsilateral pupillary changes;
4. Any irreversible coagulation disorder or known coagulopathy; platelet count <100,000; INR >1.4; or use of anticoagulant medication within 7 days before the current hemorrhage;
5. Current or probable pregnancy;
6. Patients with concurrent severe illness likely to influence outcome assessment;
7. Difficulty in follow-up or poor compliance due to any cause.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Robot-Assisted Endoscopic Minimally Invasive Surgery; Neurosurgeons participating in the robot-assisted endoscopic procedure must be qualified doctors who have completed standardized training and certification by the coordinating center. They must be capable of performing endoscopic hematoma evacuation and managing common intraoperative complications. Each certified surgeon is required to regularly review the surgical protocol and the technical components of the procedure. Surgical trajectory: The incision and burr-hole location are determined using an AI-integrated neuroimaging automatic surgical trajectory planning system. The planning principles include, but are not limited to: avoiding critical functional areas such as language and motor cortices; avoiding vascular-dense regions; and selecting the individualized optimal trajectory based on the three-dimensional morphology and spatial orientation of the hematoma. Plan review by supporting units: All preoperative imaging data and trajectory plans are automatically stored and uploaded	Procedure: Robot-Assisted Endoscopic Minimally Invasive Surgery; Neurosurgeons participating in the robot-assisted endoscopic procedure must be qualified doctors who have completed standardized training and certification by the coordinating center. They must be capable of performing endoscopic hematoma evacuation and managing common intraoperative complications. Each certified surgeon is required to regularly review the surgical protocol and the technical components of the procedure. Surgical trajectory: The incision and burr-hole location are determined using an AI-integrated neuroimaging automatic surgical trajectory planning system. The planning principles include, but are not limited to: avoiding critical functional areas such as language and motor cortices; avoiding vascular-dense regions; and selecting the individualized optimal trajectory based on the three-dimensional morphology and spatial orientation of the hematoma. Plan review by supporting units: All preoperative imaging data and trajectory plans are automatically stored and uploaded b
Sham Comparator: Traditional Surgical Approaches; A small craniotomy or large bone flap craniotomy is performed to microscopically evacuate the basal ganglia hematoma, followed by electrocoagulation for hemostasis. Depending on preoperative brain herniation or intraoperative brain swelling, the surgeon may decide whether to remove the bone flap.	Procedure: Traditional Surgical Approaches; A small craniotomy or large bone flap craniotomy is performed to microscopically evacuate the basal ganglia hematoma, followed by electrocoagulation for hemostasis. Depending on preoperative brain herniation or intraoperative brain swelling, the surgeon may decide whether to remove the bone flap.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) score at 6 months	The primary analysis will compare differences between the two groups based on utility-weighted mRS.	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal shift in mRS scores at 6 months (ordinal shift)	The difference in the distribution of scores on the modified Rankin Scale (mRS, range 0-6) between the treatment and control groups was assessed at 6 months after onset (or treatment) using a shift analysis.	up to 6 months
Favorable functional outcome at 6 months (mRS 0-1)	The proportion of patients achieving an excellent functional outcome (defined as mRS score of 0 or 1) at 6 months.	up to 6 months
Functional independence at 6 months (mRS 0-2)	The proportion of patients achieving functional independence (defined as mRS score of 0, 1, 2) at 6 months.	up to 6 months
Health-related quality of life (HRQoL) at 6 months, assessed by the EQ-5D-5L questionnaire	Assessed using the EQ-5D-5L questionnaire at 6 months post-onset/post-surgery. The instrument comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with five levels of severity, plus a Visual Analogue Scale (EQ-VAS)	up to 6 months
Total length of hospital stay	Total length of hospital stay is defined as the number of days from admission to discharge from the neurosurgical unit.	up to 6 months
Cognitive function at 6 months	Cognitive status will be evaluated at the 6-month follow-up visit using the Montreal Cognitive Assessment (MoCA).	up to 6 months
Hematoma clearance rate at 48 hours postoperatively	Hematoma volumes were quantified using semi-automated planimetric analysis (e.g., 3D Slicer software) on standard non-contrast CT scans obtained at baseline and 48 hours after surgery. This method was chosen to ensure accuracy over the ellipsoid (ABC/2) method, particularly for irregular post-operative hematoma shapes	up to 6 months
Costs during hospitalization	Direct medical costs incurred during the inpatient period were extracted from the hospital information system. Costs were categorized into four domains: (1) surgical and anesthesia fees (including disposables); (2) ward and ICU nursing fees; (3) medication costs; and (4) diagnostic imaging and laboratory fees	up to 6 months
Intraoperative blood loss	Blood loss was estimated using the standard formula: $Total Loss = (Volume_{suction} - Volume_{irrigation}) + (Weight_{wet\ gauze} - Weight_{dry\ gauze}).	up to 6 months
Incidence of rebleeding within 14 days	Rebleeding was defined as a radiographic expansion of the hematoma volume by > 33% or an absolute increase of > 5 mL on follow-up CT scans compared with the post-operative baseline CT.	up to 6 months
Incidence of related complications within 14 days, including pulmonary infection, aphasia, seizures, and deep vein thrombosis of the lower limbs	Incidence of perioperative complications within 14 days. Specific Complications: Pulmonary Infection: Defined according to CDC criteria, requiring radiographic evidence of new infiltrates combined with clinical signs (fever, purulent sputum). Aphasia: Defined as new-onset language deficits or worsening of existing aphasia (NIHSS language subscore increase ≥ 1). Seizures: Documented clinical epileptic events confirmed by neurological examination or EEG. Deep Vein Thrombosis (DVT): Confirmed by Doppler ultrasonography screening performed between postoperative days 7 and 14.	up to 6 months

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Nanchang University; Huashan Hospital; Second Affiliated Hospital, School of Medicine, Zhejiang University; Hebei General Hospital; The First Affiliated Hospital of Zhengzhou University; China-Japan Friendship Hospital; Shanghai East Hospital; Renmin Hospital of Wuhan University; Second Affiliated Hospital of Xi'an Jiaotong University; Shaoxing Central Hospital; Jinhua Central Hospital; First Affiliated Hospital of Chongqing Medical University; The Affiliated Hospital of Inner Mongolia Medical University; First Affiliated Hospital of Harbin Medical University; The First People's Hospital of Lianyungang; The Second Affiliated Hospital of Kunming Medical University; First Affiliated Hospital of Guangxi Medical University; Jinshan Hospital Fudan University; Affiliated Hospital of Nantong University; Minhang District Central Hospital of Shanghai; Aerospace Center Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: multicenter; controlled; umbrella trial; Large Basal Ganglia Hemorrhage; Al-assisted robotic guidance; Randomlzed
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Hematoma
• Other Study ID Numbers: SQ2023AAA030147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No