Dose-effect Relationship of Rt-PA on ICH Evacuation

NCT02472574 | Unknown Phase 2 DMC

• 1 other identifier: 20150403
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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。

Conditions

Hypertensive Intracerebral Hemorrhage

Keywords

Intracerebral Hemorrhage; minimally invasive surgery; recombinant tissue plasminogen activator; Dose-effect Relationship

Outcome Measures

Primary Outcomes (1)

• rate of clot size removal

  baseline to 24 hours(±12) post the last dose of rt-PA

Secondary Outcomes (8)

• 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

Study Arms (3)

0.3 mg

EXPERIMENTAL

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; Drug: rt-PA

0.5 mg

EXPERIMENTAL

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; Drug: rt-PA

1.0 mg

EXPERIMENTAL

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; Drug: rt-PA

Interventions

YL-1 type of intracranial hematoma puncture needle DEVICE

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.

Also known as: aspiration drainage

0.3 mg; 0.5 mg; 1.0 mg

rt-PA DRUG

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.

Also known as: recombinant tissue plasminogen activator

0.3 mg; 0.5 mg; 1.0 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80.
• GCS \< 14 or a NIHSS \> or equal to 6.
• Spontaneous supratentorial ICH ≥ 20 mL diagnosed using radiographic imaging (CT, CTA, etc.)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

Related Publications (4)

• 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.

  PMID: 19066101 BACKGROUND

• 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.

  PMID: 23391763 BACKGROUND

• 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.

  PMID: 24710926 BACKGROUND

• 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.

  PMID: 22274965 BACKGROUND

MeSH Terms

Conditions

Intracranial Hemorrhage, Hypertensive; Cerebral Hemorrhage

Interventions

Suction; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drainage; Surgical Procedures, Operative; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Zhu Suiqiang, doctor

  Hubei Tongji Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director of the neurology

Study Record Dates

• First Submitted: May 17, 2015
• First Posted: June 16, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: June 16, 2015

Record last verified: 2015-06

Locations

CN (1)