Dose-effect Relationship of Rt-PA on ICH Evacuation

Sponsor

Tongji Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02472574

Collaborator

(none)

108

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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。

Condition or Disease	Intervention/Treatment	Phase
Hypertensive Intracerebral Hemorrhage	Device: YL-1 type of intracranial hematoma puncture needle Drug: rt-PA	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.3 mg 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 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. Other Names: aspiration drainage Drug: rt-PA 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. Other Names: recombinant tissue plasminogen activator
Experimental: 0.5 mg 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 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. Other Names: aspiration drainage Drug: rt-PA 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. Other Names: recombinant tissue plasminogen activator
Experimental: 1.0 mg 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 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. Other Names: aspiration drainage Drug: rt-PA 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. Other Names: recombinant tissue plasminogen activator

Arm

Intervention/Treatment

Experimental: 0.3 mg

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

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.

Other Names:

aspiration drainage

Drug: rt-PA

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.

Other Names:

recombinant tissue plasminogen activator

Experimental: 0.5 mg

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

Other Names:

aspiration drainage

Drug: rt-PA

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.

Other Names:

recombinant tissue plasminogen activator

Experimental: 1.0 mg

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

Other Names:

aspiration drainage

Drug: rt-PA

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.

Other Names:

recombinant tissue plasminogen activator

Outcome Measures

Primary Outcome Measures

rate of clot size removal [baseline to 24 hours(±12) post the last dose of rt-PA]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.