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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03519737
Recruitment Status : Active, not recruiting
First Posted : May 9, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
Cerevast Medical, Inc.

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


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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

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)




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.



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03519737


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

Publications:
Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016 Jan 26;133(4):e38-360. doi: 10.1161/CIR.0000000000000350. Epub 2015 Dec 16. Erratum in: Circulation. 2016 Apr 12;133(15):e599.
Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama à Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17. Erratum in: N Engl J Med. 2015 Jan 22;372(4):394.

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Responsible Party: Cerevast Medical, Inc.
ClinicalTrials.gov Identifier: NCT03519737     History of Changes
Other Study ID Numbers: CM-CP-01
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Cerevast Medical, Inc.:
Stroke
Acute Stroke

Additional relevant MeSH terms:
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Tissue Plasminogen Activator
Stroke
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action