Penumbral Based Novel Thrombolytic Therapy in Acute Ischemic Stroke

NCT ID: NCT02101606

Last Updated: 2018-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2017-11-30

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. 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. It is hypothesized that treatment with TNK in patients with penumbral patterns will be associated with reperfusion, early neurological improvement and penumbral tissue salvage.

Study Design The study is planned as an open label feasibility and safety study of acute treatment with TNK in ischemic stroke patients with penumbral patterns evident on advanced MRI or CT perfusion sequences.

Study Outcomes The primary outcome of this study is a safety endpoint, specifically the frequency of symptomatic hemorrhagic transformation evident on MRI or CT images on 24 h or day 5 scans. The ECASS II system for rating hemorrhagic transformation will be applied to all GRE/SWI images

Significance Current treatment paradigms have not permitted success of tPA to be extended beyond narrow and limiting therapeutic window of 4.5 hours. Clearly, more effective patient selection criteria are required. Penumbral imaging is biologically plausible, practical and has been shown to be predictive of outcome. Application of these imaging techniques to the acute stroke population is the most promising strategy for extending the therapeutic window and for introducing superior thrombolytic agents.

Conditions

Cerebral Infarction; Brain Ischemia; Stroke

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tenecteplase

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. All patients will be 18 years or older.

3. Baseline NIHSS must be 4-18 inclusive.

4. 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.

5. Female patients of child-bearing potential will have a negative pregnancy test prior to enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Ken Butcher

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenneth Butcher, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta

Edmonton, Alberta, Canada

Countries

Canada

Other Identifiers

Pro00009050

Identifier Type: -

Identifier Source: org_study_id