Aureva Transcranial Ultrasound Device With tPA in Patients With Acute Ischemic Stroke (TRUST)

November 28, 2018 updated by: Cerevast Medical, Inc.

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)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Anticipated)

596

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • The University Of Tennessee Health Science Center
    • Texas
      • Houston, Texas, United States, 77030
        • Memorial Hermann Hospital - Texas Medical Center (TMC)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
SHAM_COMPARATOR: Control group (tPA + sham TUS)
Control group (tPA + sham TUS) During the primary phase of the study, subjects will be randomized 1:1
Device: 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
Other Names:
  • Aureva Headframe (Sham TUS) with Tissue Plaminogen Activator (tPA)
ACTIVE_COMPARATOR: Treatment group (tPA + TUS)
Treatment group (tPA + TUS): Lead-in phase and Primary phase
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
Other Names:
  • Aureva Headframe (TUS) with Tissue Plaminogen Activator (tPA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete recanalization measured by modified Arterial Occlusive Lesion (mAOL)
Time Frame: 90-120 minutes post TUS treatment before EVT
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
modified Rankin Scale (mRS) score 0-2
Time Frame: 90 days +/- 10 days
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
Neurologic Status at 24 hours post treatment measured by National Institute of Health's Stroke Scale (NIHSS).
Time Frame: 24 hours post TUS treatment
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
Partial or complete recanalization as measured by mAOL score of 2-3.
Time Frame: 90-120 minutes post TUS treatment before EVT
See description in Primary Outcome Measure.
90-120 minutes post TUS treatment before EVT
Partial or complete recanalization as measured by Thrombolysis In Cerebral Ischemia (TICI) score of 2-3
Time Frame: 90-120 minutes post TUS treatment before EVT
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cerevast Medical, Inc.

Investigators

  • Principal Investigator: Andrei V Alexandrov, MD, University of Tennessee Health Science Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 17, 2018

Primary Completion (ANTICIPATED)

November 30, 2021

Study Completion (ANTICIPATED)

December 31, 2021

Study Registration Dates

First Submitted

April 17, 2018

First Submitted That Met QC Criteria

April 26, 2018

First Posted (ACTUAL)

May 9, 2018

Study Record Updates

Last Update Posted (ACTUAL)

November 30, 2018

Last Update Submitted That Met QC Criteria

November 28, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CM-CP-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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