Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)

Completed

Phase 2 Results

Trial Description

To determine whether the extent of the ischemic penumbra apparent on perfusion-diffusion MRI can be used to identify patients who would respond positively and safely to tissue plasminogen activator (tPA) beyond 3 hours post-stroke.

Conditions

Interventions

Trial Design

  • Allocation: Randomized
  • Masking: Double-Blind
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

All 100 participants will have baseline MRI studies with gadolinium contrast, including DWI, perfusion-weighted imaging (PWI), and magnetic resonance angiography (MRA). All participants will be randomized into tPA or placebo groups within 3-6 hours after stroke onset. tPA for all patients will be dosed at 0.9 mg/kg, with a maximum dose of 90 mg, and will be delivered with 10% injected in a 1-minute bolus, and the remainder infused over 60 minutes. Placebo infusions will be delivered in an identical manner. Patients will be observed every 15 minutes for 2 hours, every hour for 4 hours, every 2 hours for 12 hours, and every 4 hours until reviewed by an investigator. All patients will receive repeat MRI studies (DWI, PWI, MRA) at 3-5 days, and at 90 days post-stroke.

Outcomes

Type Measure Time Frame Safety Issue
Primary Change in the size of the ischemic lesion between baseline and follow-up studies, as visualized with diffusion-weighted imaging (T2 lesion volume - acute DWI volume).
Secondary Reperfusion defined as change between acute PWI volume(3-6 hours) and subacute PWI volume (3-5 days); symptomatic hemorrhagic transformation at day 3, as assessed by MRI; infarct volume, as measured with T2-weighted MRI; degree of recanalization of the MCA; proportion of patients making an 8-point improvement in their NIHSS score or outcome score of 0,1; percentage of patients reaching an MRS score of 0 - 2.
Primary Primary Hypothesis - lesion growth
Primary In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA.
Secondary Secondary Hypotheses
Secondary In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA.
Secondary Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA.
Secondary That the proportion of patients achieving good neurological outcome (an 8 point improvement in NIH-SS or outcome NIH-SS of 0, 1) will be greater in those patients with a penumbra receiving tPA.
Secondary Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA.
Secondary Reperfusion (greater than 90% PWI lesion reduction, or recanalisation on MRA, between the acute and sub-acute interval), will be increased (in patients with penumbra) receiving tPA.
Secondary In patients with malignant mismatch (Definition DWI 100ml or more and / or PWI 100ml or more) there will be unfavourable clinical outcome (even if there is attenuation of growth).

Sponsors