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

• ClinicalTrials.gov Identifier: NCT03519737
• Recruitment Status: Unknown
• First Posted: May 9, 2018
• Last Update Posted: November 30, 2018
• Sponsor: Cerevast Medical, Inc.
• Information provided by (Responsible Party): Cerevast Medical, Inc.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke	Device: tPA in combination with the Sonolysis Headframe (TUS); Device: tPA in combination with the Sonolysis Headframe (Sham TUS)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 596 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Sham control and active insonation. During lead-in phase for the first 40 subjects, only active insonation will be programmed.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Blinding is achieved through operator entry of a randomization variable obtained from IWRS at the time of enrollment and randomization. This randomization variable (A or B), the meaning of which is blinded to the operator, is entered into the control box and determines the mode of the device as either active insonation or sham insonation.
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: August 17, 2018
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

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 Name: 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 Name: Aureva Headframe (TUS) with Tissue Plaminogen Activator (tPA)

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Tennessee

The University of Tennessee Health Science Center

Memphis, Tennessee, United States, 38163

United States, Texas

Memorial Hermann Hospital - Texas Medical Center (TMC)

Houston, Texas, United States, 77030

Sponsors and Collaborators

Cerevast Medical, Inc.

Investigators

• Principal Investigator: Andrei V Alexandrov, MD; University of Tennessee

More Information

Publications:

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• Responsible Party: Cerevast Medical, Inc.
• ClinicalTrials.gov Identifier: NCT03519737
• Other Study ID Numbers: CM-CP-01
• First Posted: May 9, 2018
• Last Update Posted: November 30, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Cerevast Medical, Inc.:

Stroke; Acute Stroke

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis