Safety of Intravenous Thrombolysis for Wake-up Stroke

NCT01183533 | Completed Phase 2 Results DMC

• 1 other identifier: HSC-MS-10-0195
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose is to demonstrate the safety of intravenous tissue plasminogen activator (IV t-PA) in ischemic stroke patients who present to the emergency department (ED) after awakening with the symptoms of suspected ischemic stroke.

Conditions

Ischemic Stroke

Keywords

Wake-Up Stroke; Ischemic stroke; ischemic stroke patients who wake-up with their symptoms

Outcome Measures

Primary Outcomes (1)

• Frequency of Symptomatic Hemorrhagic Transformation Safety of iv Rt-PA in Wake up Stroke Patients

  The primary outcome of this study is the frequency of symptomatic hemorrhagic transformation evident within 24 hours of treatment with IV t-PA. Symptomatic was defined as significant clinical deterioration with at least a 4 point or more increase in the NIH Stroke scale.

  24 hours

Secondary Outcomes (2)

• 90-day Modified Rankin Scale (mRS) Score 0 or 1

  90 days

• Mortality

  90 days

Study Arms (1)

off label rt-PA used

EXPERIMENTAL

off label rt-PA used on all subject enrolled within 3 hours of waking with stroke symptoms at the standard of care dose.

Drug: Alteplase (iv t-PA)

Interventions

Alteplase (iv t-PA) DRUG

0.9 mg/kg (maximum of 90 mg) IV t-PA will be administered with 10% bolus given over 1 minute, the rest given as an infusion over the remaining hour.

Also known as: Activase®, Alteplase, tissue plasminogen activator, t-PA

off label rt-PA used

Eligibility Criteria

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

You may qualify if:

• Suspected acute ischemic stroke that occurred during sleep or patients who wake up with focal neurological symptoms. This includes all patients who were last known to be neurologically normal the night before,but then found upon awakening with stroke deficits. It will be considered that the last known onset time is the time when the patient was last known to be well.
• to 80 years old
• NIHSS (National Institutes of Health Stroke Scale) ≤25
• Blood Pressure ≤185 mmHg systolic \& ≤110 mmHg diastolic at the time of enrollment.
• Treatment of higher systolic BP is permitted, prior to enrollment
• IV t-PA must be given within 3 hours of awakening from sleep
• Female patients of child-bearing potential must have a negative pregnancy test prior to enrollment

You may not qualify if:

• Prior ischemic stroke within 3 months of the presenting event
• History of intracranial hemorrhage
• Known secured or unsecured cerebral aneurysm or vascular malformation
• Inability to control systolic BP \> 185 mmHg or diastolic BP \> 110 mmHg with IV anti-hypertensive medications
• Known coagulopathy or evidence of active bleeding
• Surgical procedures, biopsy, subclavian venous or arterial puncture, trauma within 14 days of the event
• Gastrointestinal or genitourinary bleeding within 14 days of the event
• Treated with IV heparin within the previous 24 hours \& an abnormal (partial thromboplastin time) PTT
• Oral anticoagulants \& an (international normalized ratio) INR \>1.7
• Platelet count \<100,000
• Venous glucose either \<50 or \>450
• Any patient who qualifies for this protocol should not be treated with (intra-arterial therapy) IAT If the treating physician believes a patient should undergo IAT, those patients should be identified a priori and not enrolled into this protocol

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Genentech, Inc.: collaborator

Study Sites (3)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Swedish Medical Center

Englewood, Colorado, 80113, United States

Location

UT-Houston Health Science Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Barreto AD, Fanale CV, Alexandrov AV, Gaffney KC, Vahidy FS, Nguyen CB, Sarraj A, Rahbar M, Grotta JC, Savitz SI; Wake-Up Stroke Investigators. Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke. Ann Neurol. 2016 Aug;80(2):211-8. doi: 10.1002/ana.24700. Epub 2016 Jul 12.

  PMID: 27273860 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The single-arm / open-label design suffers from limitations such as possible bias in patient selection and outcome assessment. However, adverse events were adjudicated by the DSMB. Small trial size warrants caution; further studies are necessary.

Results Point of Contact

• Title: Sean I. Savitz, MD
• Organization: University of Texas Health Science Center at Houston

sean.i.savitz@uth.tmc.edu

713-500-7083

Study Officials

• Sean I Savitz, MD

  UT-Houston Health Science Center

  PRINCIPAL INVESTIGATOR

• Andrew D Barreto, MD

  Study Co-PI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 16, 2010
• First Posted: August 17, 2010
• Study Start: July 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2014
• Last Updated: November 25, 2014
• Results First Posted: November 25, 2014

Record last verified: 2014-11

Locations

US (3)