Phase 3, Randomized, Placebo-Controlled, Double-Blinded Trial of the Combined Lysis of Thrombus With Ultrasound and Systemic Tissue Plasminogen Activator (tPA) for Emergent Revascularization in Acute Ischemic Stroke "CLOTBUST-ER"

Terminated

Phase 3 Results N/A

Trial Description

This is a randomized, placebo-controlled, phase 3 clinical trial to evaluate the efficacy and safety of transcranial ultrasound (US) as an adjunctive therapy to tissue plasminogen activator (tPA) treatment in subjects with acute ischemic stroke.

Detailed Description

The primary objective of this trial is to provide information regarding the efficacy of a combined treatment with transcranial US and systemic tPA (Target group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke. The primary efficacy endpoint is functional outcome at 3 months from stroke onset (modified Rankin Score ordinal shift analysis). The primary safety endpoint is the proportion of subjects in the Target vs Control group experiencing symptomatic intracranial hemorrhage (sICH) within 24 hours of treatment.

Conditions

Interventions

  • Tissue plasminogen activator (Activase┬«)Drug
    Other Names: Alteplase; tPA
    Intervention Desc: Thrombolytic
  • Ultrasound Device
    Intervention Desc: Medical imaging technique used to visualize muscles, tendons, and many internal organs, their size, structure and any pathological lesions with real time tomographic images.
  • Placebo Drug
    Intervention Desc: A placebo is a substance or procedure which a patient accepts as a medicine or therapy but which has no specific therapeutic activity for the condition.
  • Perflutren Lipid Microsphere (DEFINITY)Drug
    Other Names: Definity
    Intervention Desc: The perflutren lipid microspheres preparation contains very small gas-filled lipid microspheres that reflect the sound waves and help create a better picture.
  • Transcranial ultrasound as an adjunctive therapy to tPA Device
    Intervention Desc: tPA per approved labeling administered over 60 minutes Ultrasonic headframe with active insonation for 120 minutes
    ARM 1: Kind: Experimental
    Label: Target group
    Description: A combined treatment with transcranial US and systemic tPA
  • Standard of care tPA therapy for acute ischemic stroke Drug
    Intervention Desc: tPA per approved labeling administered over 60 minutes Ultrasonic headframe with sham (inactive) insonation for 120 minutes
    ARM 1: Kind: Experimental
    Label: Control group
    Description: Systemic tPA alone

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized to one of two arms: combined treatment with perflutren lipid microspheres, transcranial US and systemic tPA (Target group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke.

Outcomes

Type Measure Time Frame Safety Issue
Primary To compare clinical recovery rates (modified Rankin score 0-1) at 3 months after stroke onset.
Secondary A comparison of the rates of symptomatic intracerebral hemorrhage within 0-36 hours from initiation of treatment.
Primary Modified Rankin score 0-1 3 months Yes
Secondary Symptomatic intracerebral hemorrhage 0-36 hours from treatment Yes
Primary Modified Rankin score ordinal shift analysis 3 months Yes

Sponsors