Clinical trial NCT02472574: Dose-effect Relationship of Rt-PA on ICH Evacuation
Official title: Phase 2 Study of Rt-PA Dose-effect Relationship on ICH Evacuation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hypertensive Intracerebral Hemorrhage
Keywords: Intracerebral Hemorrhage
minimally invasive surgery
recombinant tissue plasminogen activator
Dose-effect Relationship
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2015-06-16
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: rate of clot size removal
timeFrame: baseline to 24 hours(±12) post the last dose of rt-PA
Secondary outcomes:
measure: Mortality
timeFrame: 30 days
measure: Procedure related mortality
timeFrame: 30 days
measure: Incidence of intracranial infection
timeFrame: 30 days
measure: Rate of rebleeding
timeFrame: 30 days
measure: Glasgow outcome scale gos
timeFrame: 90 days
measure: Glasgow outcome scale gos
timeFrame: 180 days
measure: Rankin stroke impact scale
timeFrame: 90 days
measure: Rankin stroke impact scale
timeFrame: 180 days
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Hubei Tongji Hospital
name: Zhu Suiqiang, doctor
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1007/978-3-211-09469-3_30.
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.
citation: 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):165-171. doi: 10.1007/s11596-014-1252-x. Epub 2014 Apr 8.
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.