Aureva Transcranial Ultrasound Device With tPA in Patients With Acute Ischemic Stroke

Acute Ischemic Stroke Clinical Trial

— TRUST  

Official title:

A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of the Aureva Transcranial Ultrasound Device With Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke (TRUST)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03519737
• Other study ID #: CM-CP-01
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 17, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: November 2018
• Source: Cerevast Medical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, placebo controlled, double-blind phase 3 clinical study to evaluate the efficacy and safety of transcranial ultrasound (TUS) using the Sonolysis Headframe as an adjunctive therapy to intravenous (IV) tissue plasminogen activator (tPA) therapy in subjects with acute ischemic stroke that initially present at non-endovascular (EVT) treating hospitals that have established transport services in place to transfer subjects to hospitals capable of performing EVT.

Description:

The primary objective of this study is to assess the safety and efficacy of TUS using the Sonolysis Headframe in combination with systemic tPA (Treatment group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke.

Number of Subjects Required:

Lead-in Phase: 40 subjects in the U.S.; Primary Phase: 556 total enrolled subjects (278 per arm)

Number of Study Centers:

Lead-in Phase: Up to 20 Institutions in U.S.; Primary Phase: Up to 70 Institutions worldwide

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 596
• Est. completion date: December 31, 2021
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subjects with acute ischemic stroke

2. Subjects that initially present at non-EVT treating hospitals that have established transport services in place to transfer subjects to hospitals capable of performing EVT

3. Males or females 18 - 80 years of age

4. Subjects presenting within time window for IV tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms

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

6. Subjects that in the opinion of the treating physician require treatment with full dose of IV tPA (0.9mg/kg) as standard of care per institutional standards

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

8. Pre-morbid mRS of 0-1

9. Arterial occlusion in the middle cerebral artery (MCA) M1 or proximal M2, intracranial carotid T, anterior cerebral artery (ACA) A1, basilar, proximal posterior cerebral artery (PCA) P1 or intracranial tandem lesions in these locations visible on CT angiography (CTA)

10. 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 and no later than 15 minutes after standard of care tPA administration

Exclusion Criteria:

1. Tandem lesions where one lesion is extracranial (carotid or vertebral artery)

2. ASPECTS score < 6 on non contrast CT or ischemic changes that in the opinion of the investigator would be medically inappropriate for reperfusion therapy

3. Poor collateral circulation defined as minimal or no pial collaterals in >50% of the ischemic territory

4. Expected time between activation of Sonolysis Headframe and initiation of EVT < 90 minutes

5. Pregnant or breast feeding women, clinical signs of pericarditis, sepsis or any other serious medical illness likely to interact with treatment, confounding preexistent neurological or psychiatric disease or test values that, in the opinion of the investigator, pose significant risk to the subject and warrant exclusion from the study

6. Impaired renal function defined as eGFR < 60 mL/min/1.73 m2

7. No permanent address or phone number

8. Any investigational drug <14 days prior to study participation

9. Subjects with known allergy to x-ray contrast material

10. Subjects with any standard contraindication for intravenous tPA therapy as per local or national guidelines

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Stroke

Intervention

Device:
• tPA in combination with the Sonolysis Headframe (TUS)
tPA: 60 minutes per approved labeling TUS insonation via the Sonolysis Headframe: minimum 90 minutes - maximum 120 minutes
• tPA in combination with the Sonolysis Headframe (Sham TUS)
tPA per approved labeling Sham (inactive) TUS insonation via the Sonolysis Headframe: minimum 90 minutes - maximum 120 minutes

Locations

Country	Name	City	State
United States	Memorial Hermann Hospital - Texas Medical Center (TMC)	Houston	Texas
United States	The University of Tennessee Health Science Center	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Cerevast Medical, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (25)

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete recanalization measured by modified Arterial Occlusive Lesion (mAOL)	Complete recanalization of the primary occluded vessel as measured by the modified Arterial Occlusive Lesion (mAOL) scoring system. The mAOL assigns a score from 0 to 3, which represents the range from no recanalization to complete recanalization based on either the presence (grade 2 or 3) or absence (grades 0 or 1) of any downstream flow.	90-120 minutes post TUS treatment before EVT
Secondary	modified Rankin Scale (mRS) score 0-2	Functional dependence at 90 days as measured by the modified Rankin Scale (mRS). The mRS consists of 7 grades, (0-6), with 0 corresponding to no symptoms and 6 corresponding to death. For this study, functional independence will be defined as those subjects that achieve a mRS score of 0-2 at 90 days.	90 days +/- 10 days
Secondary	Neurologic Status at 24 hours post treatment measured by National Institute of Health's Stroke Scale (NIHSS).	NIHSS has 15 items. Ratings for each item are scored on a 0-3 to 0-5 scale, with a total score of 0 for normal and 42 for maximally impaired.	24 hours post TUS treatment
Secondary	Partial or complete recanalization as measured by mAOL score of 2-3.	See description in Primary Outcome Measure.	90-120 minutes post TUS treatment before EVT
Secondary	Partial or complete recanalization as measured by Thrombolysis In Cerebral Ischemia (TICI) score of 2-3	TICI Scale: [0] - No antegrade flow beyond the point of occlusion. [1] - The contrast material passes beyond the area of obstruction but fails to opacify the entire cerebral bed distal to the obstruction. [2] - The contrast material passes beyond the obstruction and opacifies the arterial bed distal to the obstruction. However, the rate of entry of contrast into the vessel distal to the obstruction and/or its rate of clearance from the distal bed are perceptibly slower than its entry into and/or clearance from comparable areas not perfused by the previously occluded vessel. [3] - Antegrade flow into the bed distal to the obstruction occurs as promptly as into the obstruction and clearance of contrast material from the involved bed is as rapid as from an uninvolved other bed of the same vessel or the opposite cerebral artery.	90-120 minutes post TUS treatment before EVT