Penumbral Based Novel Thrombolytic Therapy in Acute Ischemic Stroke (TIAS)
|ClinicalTrials.gov Identifier: NCT02101606|
Recruitment Status : Completed
First Posted : April 2, 2014
Last Update Posted : April 6, 2018
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.
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Cerebral Infarction Brain Ischemia Stroke||Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Penumbral Based Novel Thrombolytic Therapy in Acute Ischemic Stroke|
|Study Start Date :||October 2009|
|Actual Primary Completion Date :||November 2017|
|Actual Study Completion Date :||November 2017|
Drug: 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.
- Frequency of symptomatic hemorrhagic transformation evident on MRI or CT [ Time Frame: 2-5 days post treatment ]The ECASS II system for rating hemorrhagic transformation will be applied to all GRE / SWI / CT images
- Imaging: Change in volume of hypoperfused tissue at follow up perfusion imaging [ Time Frame: At 24 hours follow up perfusion scan ]The primary efficacy endpoint is the change in volume of hypoperfused tissue, defined as that having a Tmax delay of >4s, between the acute and 24 hour post-treatment PWI or CTP scans. It is hypothesized that the perfusion deficit volume will decrease significantly between the two scans.
- Clinical: Clinical improvement as shown by change in NIHSS [ Time Frame: At 24 h, 3, 30 and 90 days ]All follow-up neurological examinations and scoring will be performed during face-to-face examinations in the Stroke Clinic or, if necessary, in the facility where the patient is at that time. Day 90 is the standard time point for measuring outcome in stroke trials, as most patients destined to improve will have had the bulk of their neurological recovery by then. All clinical assessments will be done by study personnel certified in NIHSS administration and blinded to image analysis. All adverse events, including those related to imaging procedures will be recorded
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02101606
|University of Alberta|
|Edmonton, Alberta, Canada, T6G2B7|
|Principal Investigator:||Kenneth Butcher, MD, PhD||University of Alberta|