Dose-effect Relationship of Rt-PA on ICH Evacuation

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to determine the optimal dose of rt-PA in the treatment of intracerebral hemorrhage (ICH) using a combination of minimally invasive surgery and clot lysis with rt-PA。

Detailed Description
-----------------
The minimally invasive surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) is one of the best choices in the treatment of a large-scale deep supratentorial intracerebral hematoma. It uses hardware access technology, in a relatively short time to enter the hematoma center with favourable accuracy and safety. The dose of rt-PA range from 0.3 mg to 4.0 mg in different research。We propose to determine the optimal dose of rt-PA with three dose control groups.

Official Title
-----------------
Phase 2 Study of Rt-PA Dose-effect Relationship on ICH Evacuation

Conditions
-----------------
Hypertensive Intracerebral Hemorrhage

Intervention / Treatment
-----------------
* Device: YL-1 type of intracranial hematoma puncture needle
* Drug: rt-PA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-80. GCS < 14 or a NIHSS > or equal to 6. Spontaneous supratentorial ICH ≥ 20 mL diagnosed using radiographic imaging (CT, CTA, etc.) Symptoms less than 24 hours prior to diagnostic CT(dCT) scan (an unknown time of symptom onset is exclusionary). Six-hour clot size equal to the most previous clot size (within 5 mL) as determined by additional CT scans at least 6 hours apart using the ABC/2 method. Intention to initiate surgery between 12 and 72 hours after after diagnostic CT. First dose can be given within 76 hours after dCT (delays for post surgical stabilization of catheter bleeding). SBP < 180 mmHg sustained for 6 hours recorded closest to time of randomization. Historical Rankin score of 0 or 1. Negative pregnancy test. Exclusion Criteria: Infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy). Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4. Intraventricular hemorrhage requiring treatment with extraventricular drainage (obstruction of third and fourth ventricles). Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease diagnosed with radiographic imaging. Any irreversible coagulopathy or known clotting disorder. or having the experience of the use of anticoagulant drug. Platelet count < 100,000, INR > 1.7, or an elevated prothrombin time (PT) or activated partial thromboplastin time (aPTT). Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization. Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease. Historical Rankin score greater than or equal to 2.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.3 mg<br>Subjects randomized to the 0.3 mg arm will undergo minimally invasive surgery with YL-1 type of intracranial hematoma puncture needle, followed by up to 4 doses of 0.3 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution. | Device: YL-1 type of intracranial hematoma puncture needle<br>* YL-1 type of intracranial hematoma puncture needle(Pat. NO.is ZL：93244252•8) was originated by Beijing WanTeFu Medical Apparatus Co.Ltd in 1997. With integration of needle and bur drill it is designed as hard tunnel.By the technique of skull self-holding, the puncture needle can being fixed in the target of haematoma for several days.This technique is convenient, simple and safe. To position haematoma's location, drills 3 millimeter holes in the localization point of puncture, then insert the drainage tube to inhale hematoma, gives the filament resolver interrupted for liquefication drainage afterward.<br>* Other names: aspiration drainage;Drug: rt-PA<br>* Up to 4 doses of 0.3 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.<br>* Other names: recombinant tissue plasminogen activator;|
| Experimental: 0.5 mg<br>Subjects randomized to the 0.5 mg arm will undergo minimally invasive surgery with YL-1 type of intracranial hematoma puncture needle,followed by up to 4 doses of 0.5 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution. | Device: YL-1 type of intracranial hematoma puncture needle<br>* YL-1 type of intracranial hematoma puncture needle(Pat. NO.is ZL：93244252•8) was originated by Beijing WanTeFu Medical Apparatus Co.Ltd in 1997. With integration of needle and bur drill it is designed as hard tunnel.By the technique of skull self-holding, the puncture needle can being fixed in the target of haematoma for several days.This technique is convenient, simple and safe. To position haematoma's location, drills 3 millimeter holes in the localization point of puncture, then insert the drainage tube to inhale hematoma, gives the filament resolver interrupted for liquefication drainage afterward.<br>* Other names: aspiration drainage;Drug: rt-PA<br>* Up to 4 doses of 0.3 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.<br>* Other names: recombinant tissue plasminogen activator;|
| Experimental: 1.0 mg<br>Subjects randomized to the 1.0 mg arm will undergo minimally invasive surgery with YL-1 type of intracranial hematoma puncture needle,followed by up to 4 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution. | Device: YL-1 type of intracranial hematoma puncture needle<br>* YL-1 type of intracranial hematoma puncture needle(Pat. NO.is ZL：93244252•8) was originated by Beijing WanTeFu Medical Apparatus Co.Ltd in 1997. With integration of needle and bur drill it is designed as hard tunnel.By the technique of skull self-holding, the puncture needle can being fixed in the target of haematoma for several days.This technique is convenient, simple and safe. To position haematoma's location, drills 3 millimeter holes in the localization point of puncture, then insert the drainage tube to inhale hematoma, gives the filament resolver interrupted for liquefication drainage afterward.<br>* Other names: aspiration drainage;Drug: rt-PA<br>* Up to 4 doses of 0.3 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.<br>* Other names: recombinant tissue plasminogen activator;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of clot size removal |  | baseline to 24 hours(±12) post the last dose of rt-PA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 30 days | 
| Procedure related mortality |  | 30 days | 
| Incidence of intracranial infection |  | 30 days | 
| Rate of rebleeding |  | 30 days | 
| Glasgow outcome scale gos |  | 90 days | 
| Glasgow outcome scale gos |  | 180 days | 
| Rankin stroke impact scale |  | 90 days | 
| Rankin stroke impact scale |  | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intracerebral Hemorrhage, minimally invasive surgery, recombinant tissue plasminogen activator, Dose-effect Relationship