Clinical trial NCT01014975: A Safety and Dose Finding Study of Plasmin (Human) Administered Into the Middle Cerebral Artery of Stroke Patients
Official title: A Phase 1/2a, Open Label, Dose Escalation, Safety Study of Intra-thrombus Plasmin (Human) Administration in Acute, Middle Cerebral Artery, Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Ischemic Stroke
Keywords: stroke
plasmin
thrombus
ischemic
middle cerebral artery
thrombolysis
intra-arterial
fibrin
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2009-11-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study tests the drug, Plasmin (Human), in patients with a stroke due to a clot in the middle cerebral artery (MCA). Plasmin is an enzyme that causes clot lysis by cleaving a clot component, fibrin. In this study, Plasmin (Human) is administered locally through a catheter to the clot within 9 hours of the stroke onset. Three doses of Plasmin (Human) (20 mg, 40 mg, and 80 mg) are being tested in 3 different groups of patients. Patients are monitored by imaging of the affected artery and functional testing.

Detailed description: This is a Phase 1/2a, open-label, multi-center, sequential dose escalation, safety study of Plasmin (Human) in acute ischemic stroke caused by middle cerebral artery occlusion documented by arteriography. Plasmin (Human) will be administered through a catheter into the thrombus within 9 hours of stroke onset. Approximately sixty-one (61) patients will be enrolled and will receive Plasmin (Human). The objectives of this study are to determine the safety of escalating doses of Plasmin (Human) and to determine the proportion of patients with treatment success, defined as partial or full recanalization.

Eligibility criteria: Inclusion Criteria:

1. 18 to 85 years of age
2. Male or female
3. New focal, potentially disabling neurologic deficit clinically localized to the MCA distribution
4. Intra-arterial therapy with Plasmin completed within 9 hours of stroke onset
5. A National Institutes of Health Stroke Scale score ≥ 4 and ≤ 25

Exclusion Criteria:

1. Intracranial procedures or intracranial or systemic bleeding within the last year
2. Intracranial neoplasm (except meningioma), septic embolism, or unsecured aneurysm
3. Active bleeding
4. History of stroke in previous 6 weeks
5. Uncontrolled hypertension
6. Renal disease or renal dialysis
7. Treatment with any plasminogen activator within the last 48 hrs.
8. Therapy with a Glycoprotein IIb/IIIa inhibitor in 5 days prior to study enrollment or at any time during study

Primary outcomes:
measure: Incidence of Symptomatic Intracranial Hemorrhage (SICH) by Dose Cohort
timeFrame: 90 days
Secondary outcomes:
Other outcomes:
Locations:
city: Heidelberg
country: Australia
facility: Heidelberg Repatriation Hospital, Melbourne
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Linz
country: Austria
facility: O.O. Landes-Nervenklinik Wagner-Jauregg
state: Upper Austria
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik Salzburg,Universitätsklinik für Neurologie
city: Clermont-Ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Clinic for Vascular and Endovascular Surgery
city: Belgrade
country: Serbia
facility: Special Hospital for Cerebrovascular Diseases "Sveti Sava"
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac, Center for Radiology Diagnostic
city: Niš
country: Serbia
facility: Clinical Center Niš, Center of Radiology
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina, Center for Radiology
city: Banská Bystrica
country: Slovakia
facility: Neurology Clinic Hospital with Policlinic of F.D. Roosevelt
city: Bratislava
country: Slovakia
facility: I. Neurology Clinic, University Hospital Bratislava
city: Martin
country: Slovakia
facility: Radiology Clinic, University Hospital Martin
city: Nitra
country: Slovakia
facility: Neurology Clinic, Faculty Hospital Nitra
city: Ružomberok
country: Slovakia
facility: Neurology Clinic, Central Military Faculty Hospital
city: L´Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital General Vall d'Hebron, Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
Study officials:
affiliation: University of California, Los Angeles
name: Jeffrey Saver, MD
role: STUDY_DIRECTOR
affiliation: Melbourne Health
name: Peter Mitchell, MD
role: STUDY_DIRECTOR
References: