Study for the Use of Alteplase in Patients Who Awaken With Stroke (AWOKE)

Alteplase for Waking Onset STROKE

This is a pilot study of thrombolytic therapy in patients with ischemic stroke who present with stroke symptoms upon awakening.

Study Overview

• Status: Withdrawn
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Alteplase (tPA)

Detailed Description

Patients with ischemic stroke are currently only eligible for the treatment with intravenous thrombolysis if the stroke is diagnosed within 4.5 hours from known onset of symptoms.

Many patients awaken with stroke and are excluded from this therapy, following current guidelines.

Patients who suffer from a stroke just before or after waking up may be candidates for thrombolysis and our study will use advanced neuroimaging to select those patients.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037-0979
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥22
2. Stroke upon awakening
3. Measurable deficit by NIHSS
4. No deficit before sleep or last seen normal before to sleep
5. Head CT with no evidence of intracranial hemorrhage.
6. Able to receive IV t-PA treatment within 2.5 hrs after patient awoke with deficit.
7. Written informed consent signed and dated by the patient (or patient's authorized representative)
8. Core lesion: ASPECTS ≥7 on MRI-DWI, CTP-CBV or CTA source imaging.
9. Mismatch of at least 20% measured by CT CVB/MMT or DWI/TTP

Exclusion Criteria:

1. Stroke or serious head trauma within the preceding 3 months
2. Major surgery or serious trauma within 14 days
3. History of intracranial hemorrhage
4. Systolic blood pressure above 185 mm Hg or diastolic blood pressure above 110 mm Hg that is not controlled after aggressive measures.
5. Rapidly improving or minor symptoms
6. Symptoms suggestive of subarachnoid hemorrhage.
7. Gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 21 days.
8. Arterial puncture at a non-compressible site within the previous 7 days
9. Seizure at the onset of stroke and considered the cause for the neurological symptom.
10. Patients who are taking anticoagulants or who had received heparin within the 48 hours preceding the onset of stroke and have an elevated partial-thromboplastin time, INR>1.7 or platelet counts below 100,000/mm3
11. Finger sticks glucose below 50 mg/dl (2.7 mmol/ Lt) or above 400 mg per deciliter (22.2 mmol/Lt) and considered the cause for the neurological symptom.
12. Active internal bleeding
13. Pregnancy in women of child-bearing potential (must have pregnancy test, urine or blood, prior to therapy).
14. Lumbar puncture within 7 days.
15. Known co-morbid conditions likely to complicate therapy or interfere with patient assessment, such us: heart failure stage 4, severe dementia, end-stage AIDS, pericarditis, cirrhosis or known cancer.
16. Unable to obtain CTA or perfusion brain studies (PWI or CTP)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alteplase; Alteplase 0.9mg/kg (maximum 90mg), 10% IV bolus over 1 minute and the remainder over one hour infusion in patients with ischemic stroke after awaking.	Drug: Alteplase (tPA); 0.9mg/KG (maximum 90mg), 10% bolus over one minutes, remainder over one hour.; Other Names: tPA; t-PA; rt-PA; Activase®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic Intracranial Hemorrhage	sICH is defined as any confluent dense hematoma occupying greater than 30% of the infarcted area with substantial space occupying effect, or any brain hemorrhage outside the infarcted area that occurs within 72 hours of tPA treatment and is associated with an increase of at least 4 points in the NIHSS.	0-72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale	A good outcome is defined as a modified Rankin Scale (mRS) of ≤1 or return to baseline mRS.	90 days
National Institutes of Health Stroke Scale (NIHSS)	An improvement of the NIHSS is defined as a 4-point improvement in the NIHSS, or NIHSS 0 measured 24 hours after treatment.	24 hours

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Scripps Health

Publications and helpful links

Helpful Links

• UCSD Stroke Center

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: June 23, 2010
• First Submitted That Met QC Criteria: June 23, 2010
• First Posted (Estimate): June 24, 2010

Study Record Updates

• Last Update Posted (Estimate): September 13, 2013
• Last Update Submitted That Met QC Criteria: September 11, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: thrombolysis; sleep; stroke; Alteplase; ischemia; tPA; t-PA; rt-PA; wake-up stroke; Activase®; thrombolytics; waking onset stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: AWOKE; 5P50NS044148 (U.S. NIH Grant/Contract)