Endoscopic Intraventricular Hematoma Evacuation Surgery Versus EVD for IVH

Endoscopic Intraventricular Hematoma Evacuation Surgery Versus External Ventricular Drainage for the Treatment of Patients With Moderate to Severe Intraventricular Hemorrhage: a Multicenter, Randomized, Controlled Trial

Intraventricular hemorrhage (IVH) accounts for about 20% of intracerebral hemorrhage, but its mortality rate is as high as 50%-80%. External ventricular drainage (EVD) can rapidly reduce intracranial pressure, but clinical practice found that drainage catheters are often blocked by blood clots and long-term thrombolytic therapy is likely to cause secondary bleeding. The application of neuroendoscopy in IVH has attracted more and more attention in recent years. Studies have shown that the use of neuroendoscopy for IVH evacuation (with EVD) has advantages over EVD alone. However, the cases of most current research are small and all of them are retrospective studies, which means lacking prospective clinical studies to provide high-quality evidence. Based on this, we intend to conduct a randomized, controlled, multi-center clinical trial to compare the prognosis of patients who undergo endoscopic IVH evacuation surgery versus those who undergo external ventricular drainage for moderate to severe IVH.

Study Overview

• Status: Unknown
• Conditions: Intraventricular Hemorrhage, Endoscopic Intraventricular Evacuation Surgery, Extraventricular Drainage
• Intervention / Treatment: Procedure: endoscopic intraventricular evacuation surgery

Detailed Description

Spontaneous Intraventricular hemorrhage (IVH) is defined as bleeding into the cerebral ventricular system caused by spontaneous rupture of brain arteries, veins and capillaries instead of trauma. IVH accounts for about 20% of cerebral hemorrhage, but its mortality rate is as high as 50%-80%. According to the results of the STICH trial, the prognosis of patients with IVH is worse than that of patients without IVH (p<0.00001); if patients with IVH have hydrocephalus, the prognosis is the worst.

According to the edition of 2015 Chinese multidisciplinary experts' consensus for spontaneous cerebral hemorrhage diagnosis and treatment and 2015 AHA/ASA spontaneous cerebral hemorrhage diagnosis and treatment guidelines, for patients with small amount of IVH without obstructive hydrocephalus, conservative treatment or continuous lumbar drainage can be effective. For patients with large amount of IVH (hematoma occupying more than 50% of the lateral ventricle, secondary obstructive hydrocephalus or obviously increased intracranial pressure), the occupancy effect is dramatic and patients are prone to suffering from hydrocephalus and cerebral palsy, in which circumstances urgent evacuation of hematoma is required, but it is controversial whether it is beneficial for the patients and whether it can improve the prognosis of patients.

As the regular treatment for IVH, external ventricular drainage (EVD) can rapidly reduce intracranial pressure, but clinical practice found that drainage catheters are often blocked by blood clots, and long-term thrombolytic therapy is likely to cause secondary bleeding. Usually, the catheters need to be removed or replaced one week after placement as for the increasing risk of infection.

The application of endoscopy in IVH has attracted more and more attention. Studies have shown that the use of endoscopy for IVH evacuation (with EVD) has advantages over EVD alone. The incidence of postoperative hydrocephalus and the need for ventricular-peritoneal shunt surgery is lower. However, the cases of most current research are small and all of them are retrospective studies. There are no such clinical trials registered at home and abroad, and that is, there is a lack of prospective high-quality clinical studies to further demonstrate the effect of endoscopic treatment for IVH.

Based on this, we intend to conduct a randomized, controlled, multi-center clinical trial to compare the prognosis of patients who undergo endoscopic IVH evacuation surgery versus those who undergo external ventricular drainage for moderate to severe IVH.

• Study Type: Interventional
• Enrollment (Anticipated): 956
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Jinling Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Age ranging from 18 to 70 years old; 2. Imaging examination shows deep brain hemorrhage breaking into the ventricles or primary intraventricular hemorrhage, and the amount of bleeding is large, more than 50% of the lateral ventricle or complete ventricle cast; 3. Graeb score > 4 points; 4. Voluntary signing of informed consent;

Exclusion Criteria:

• 1. Patients with a history of chronic obstructive pulmonary disease, coronary heart disease, chronic kidney disease, blood disorders, cancer, systemic autoimmune disease, or long-term oral corticosteroids; 2. Imaging examination shows cerebellum and brain stem hemorrhage; 3. Detected cerebrovascular diseases in CTA/MRA/MRV/DSA examinations (choose 1 or 2 examinations); 4. Ultra-early (within 72 hours) or late enhanced MRI suggests the presence of brain tumors; 5. Coagulopathy or long-term oral anticoagulant;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endoscopic Treatment; Endoscopy was performed using a rigid endoscope. The hematoma was removed by a technique using irrigation and aspiration. The ventricular drainage catheter was placed on the surgical side. Six hours after surgery, we administered 20,000 U urokinase with 5 ml saline every 8 hours through the catheter and the catheter was closed for 1 hour to allow drug-clot interaction and then reopened to allow for gravitational drainage. Subsequent CT scans were done for any safety concern or every 24 hours. Administration of urokinase was stopped when the CT scans showed that the circulation of cerebrospinal fluid is unobstructed. When CT scans showed that the intracerebral hematoma was significantly reduced and the circulation of cerebrospinal fluid is unobstructed, the catheter could be clamped for 24 h. If there was no acute intracranial pressure increase, the catheter could then be removed.	Procedure: endoscopic intraventricular evacuation surgery; According to the discussion between the patient and the doctor, the patient signed the consent form and voluntarily enrolled and subsequently the patient was included in the endoscopic intraventricular evacuation surgery group.
Active Comparator: EVD Treatment; The surgeons used a soft catheter to puncture in depth of about 5 cm. The next step was to fix the drainage catheter. Postoperative CT was done immediately to confirm positioning of the soft catheter and stability of the hematoma. Six hours or more after catheter placement, we administered 20,000 U urokinase with 5 ml saline every 8 hours and the catheter was closed for 1 h to allow drug-clot interaction and then reopened to allow for gravitational drainage. Subsequent CT scans were done for any safety concern or every 24 hours. Administration of urokinase was stopped when the CT scans showed that the circulation of cerebrospinal fluid is unobstructed. When CT scans showed that the intracerebral hematoma was significantly reduced and the circulation of cerebrospinal fluid is unobstructed, the catheter could be clamped for 24 h. If there was no acute intracranial pressure increase, the catheter could then be removed.	Procedure: endoscopic intraventricular evacuation surgery; According to the discussion between the patient and the doctor, the patient signed the consent form and voluntarily enrolled and subsequently the patient was included in the endoscopic intraventricular evacuation surgery group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival of patients at 12 months postoperatively	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin score	Modified Rankin score	preoperative, one month, three months, six months, twelve months
Proportion of patients who need ventricular-peritoneal shunt Incidence of postoperative hydrocephalus	Proportion of patients who need ventricular-peritoneal shunt Incidence of postoperative hydrocephalus	0-12 month
Incidence of postoperative intracranial infection	Incidence of postoperative intracranial infection	0-12 month
Hospital stay	Hospital stay	0-12 month
Hospitalization expenses	Hospitalization expenses	0-12 month

Collaborators and Investigators

• Sponsor: Nanjing PLA General Hospital

Publications and helpful links

General Publications

• Zhu J, Tang C, Cong Z, Yang J, Cai X, Liu Y, Ma C. Endoscopic intraventricular hematoma evacuation surgery versus external ventricular drainage for the treatment of patients with moderate to severe intraventricular hemorrhage: a multicenter, randomized, controlled trial. Trials. 2020 Jul 13;21(1):640. doi: 10.1186/s13063-020-04560-3.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 26, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Hematoma
• Other Study ID Numbers: 2019NZKY-014-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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