Dose-effect Relationship of Rt-PA on ICH Evacuation

Hypertensive Intracerebral Hemorrhage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02472574
• Other study ID #: 20150403
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 17, 2015
• Last updated: June 11, 2015
• Start date: June 2015
• Est. completion date: June 2018

Study information

• Verified date: June 2015
• Source: Tongji Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Interventional

Clinical Trial 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。

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Hypertensive Intracerebral Hemorrhage
• Intracranial Hemorrhage, Hypertensive

Intervention

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.

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.

Locations

Country	Name	City	State
China	Tongji Hospital	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Tongji Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Lian LF, Xu F, Tang ZP, Xue Z, Liang QM, Hu Q, Zhu WH, Kang HC, Liu XY, Wang FR, Zhu SQ. Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage. J Huazhong Univ Sci Technolog Med Sci. 2014 Apr;34(2):165-71. doi: 10.1007/s11596-014-1252-x. Epub 2014 Apr 8. — View Citation

Morgan T, Zuccarello M, Narayan R, Keyl P, Lane K, Hanley D. Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial. Acta Neurochir Suppl. 2008;105:147-51. — View Citation

Mould WA, Carhuapoma JR, Muschelli J, Lane K, Morgan TC, McBee NA, Bistran-Hall AJ, Ullman NL, Vespa P, Martin NA, Awad I, Zuccarello M, Hanley DF; MISTIE Investigators. Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke. 2013 Mar;44(3):627-34. doi: 10.1161/STROKEAHA.111.000411. Epub 2013 Feb 7. — View Citation

Tang ZP, Shi YH, Yin XP, Xu JZ, Zhang SM, Wang W. Modifying the details of aspiration operation may contribute to the improvement of prognosis of patients with ICH. Turk Neurosurg. 2012;22(1):13-20. doi: 10.5137/1019-5149.JTN.4219-11.0. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of clot size removal		baseline to 24 hours(±12) post the last dose of rt-PA	No
Secondary	Mortality		30 days	Yes
Secondary	Procedure related mortality		30 days	Yes
Secondary	Incidence of intracranial infection		30 days	Yes
Secondary	Rate of rebleeding		30 days	Yes
Secondary	Glasgow outcome scale gos		90 days	No
Secondary	Glasgow outcome scale gos		180 days	No
Secondary	Rankin stroke impact scale		90 days	No
Secondary	Rankin stroke impact scale		180 days	No