Dose-effect Relationship of Rt-PA on ICH Evacuation

Tongji Hospital

Status and phase: Unknown; Phase 2

Conditions: Hypertensive Intracerebral Hemorrhage

Treatments: Drug: rt-PA; Device: YL-1 type of intracranial hematoma puncture needle

Study type: Interventional

Funder types: Other

Identifiers

NCT02472574

20150403

Details and patient eligibility

About

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。

Full 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.

Enrollment: 108 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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108 participants in 3 patient groups

0.3 mg

Experimental group

Description:

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.

Treatment:

Drug: rt-PA

Device: YL-1 type of intracranial hematoma puncture needle

0.5 mg

Experimental group

Description:

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.

Treatment:

Drug: rt-PA

Device: YL-1 type of intracranial hematoma puncture needle

1.0 mg

Experimental group

Description:

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.

Treatment:

Drug: rt-PA

Device: YL-1 type of intracranial hematoma puncture needle