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
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
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.
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.
Inclusion Criteria:

 1. Males or females 18 - 80 years of age

 2. Subjects presenting within timeframe for intravenous tPA treatment approved by local
 regulatory authorities but no more than 4.5 hours from onset of symptoms

 3. No signs of intracranial bleeding on assessment by non-contrast CT

 4. Subjects with neurological deficits of a total NIHSS score ≥ 10 points

 5. Subjects that in the opinion of the treating physician require treatment with full
 dose IV tPA as standard of care per institutional standards

 6. SBP < 185 mmHg and DBP < 105 mmHg at baseline or after treatment of hypertension with
 medications prior to tPA bolus

 7. Pre-morbid modified Rankin score of 0-1

 8. Provision of informed consent as demonstrated by the subject's signature or by the
 signature of the subject's authorized legal representative on the Informed Consent
 Form in accordance with all local and national regulations

 9. Co-signature on the Informed Consent Form by a qualified member of the study staff
 signifying that, in his/her professional opinion, informed consent has been obtained
 in accordance with all local and national regulations

 10. For subjects in the optional arterial recanalization substudy:

 1. Occlusion located in the intracranial carotid tee through mid M2 or proximal A2,
 or intracranial vertebrobasilar or P1/proximal P2 segments or tandem lesions

 2. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min for patients undergoing
 CTA or MRA

 Exclusion Criteria:

 1. Subjects with primary intra-arterial thrombolysis

 2. Females who are pregnant or breast feeding

 3. Subjects receiving other investigational drugs, procedures, or therapies within 30
 days prior to study treatment

 4. Subjects with any standard contraindication for intravenous tPA therapy

 5. Significant concurrent medical/neurological conditions or test values that, in the
 opinion of the investigator, pose significant risk to the subject and warrant
 exclusion from the study