Penumbral Based Novel Thrombolytic Therapy in Acute Ischemic Stroke

NCT02101606 | Completed Phase 2

• 1 other identifier: Pro00009050
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale The only proven therapy for acute stroke is tPA within 4.5 hours of symptom onset. This is the standard of care for patients presenting to our hospital within that time frame. Thrombolysis outside the 4.5 hour window is considered only on experimental or compassionate grounds. Tenecteplase (TNK) is a genetically modified variant of tPA that has many theoretical advantages in acute stroke. Studies show that systemic plasminogen activation is higher after tPA administration, relative to TNK and this is associated with an increased risk of bleeding events. Imaging cerebral blood flow (CBF) with MRI (perfusion weighted imaging-PWI) and CT perfusion (CTP) can be performed routinely with standard clinical scanners. Patients with evidence of large volumes of tissue with low CBF, that is also structurally intact, as demonstrated by either normal signal on Diffusion weighted imaging (DWI) or normal cerebral blood volume (CBV) are considered to have penumbral patterns. Patients with penumbral patterns appear to be the ideal candidates for thrombolytic therapy, regardless of time from onset. Study Hypotheses

1. 1.The primary aim of this study is to demonstrate the feasibility and safety of TNK based thrombolysis in ischemic stroke patients presenting 4.5-24 hours after symptom onset.
2. 2.It is hypothesized that treatment with TNK in patients with penumbral patterns will be associated with reperfusion, early neurological improvement and penumbral tissue salvage.

Conditions

Cerebral Infarction; Brain Ischemia; Stroke

Keywords

Acute Stroke; Cerebral Stroke; Brain Ischemia; Perfusion Imaging; MRI, Diffusion Weighted; MRI, Perfusion Weighted

Outcome Measures

Primary Outcomes (1)

• Frequency of symptomatic hemorrhagic transformation evident on MRI or CT

  The ECASS II system for rating hemorrhagic transformation will be applied to all GRE / SWI / CT images

  2-5 days post treatment

Secondary Outcomes (2)

• Imaging: Change in volume of hypoperfused tissue at follow up perfusion imaging

  At 24 hours follow up perfusion scan

• Clinical: Clinical improvement as shown by change in NIHSS

  At 24 h, 3, 30 and 90 days

Study Arms (1)

Tenecteplase

EXPERIMENTAL

Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg)

Interventions

Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg) DRUG

TNK will be administered within 30 minutes once MRI and CTP inclusion criteria are determined to have been met.

Tenecteplase

Eligibility Criteria

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

You may qualify if:

• Acute ischemic stroke patients, within 24 hours of symptom onset. In cases where onset time can not be established, including symptoms upon waking, it will be considered to be the time when the patient was last known to be well.
• All patients will be 18 years or older.
• Baseline NIHSS must be 4-18 inclusive.
• Blood pressure (BP) must be ≤180 mmHg systolic and ≤105 mmHg diastolic at the time of enrolment. Treatment of higher systolic BP is permitted, prior to enrolment.
• Female patients of child-bearing potential will have a negative pregnancy test prior to enrollment.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G2B7, Canada

Location

MeSH Terms

Conditions

Cerebral Infarction; Brain Ischemia; Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Brain Infarction; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; 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

Study Officials

• Kenneth Butcher, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

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: Professor

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: October 1, 2009
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: April 6, 2018

Record last verified: 2018-04

Locations

CA (1)