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

NCT01098981 | Terminated Phase 3 DMC

• 1 other identifier: CEREVAST THERAPEUTICS CP-01
• Study Type: interventional
• Target: 675
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Modified Rankin score ordinal shift analysis

  The primary objective of this study is to compare clinical recovery rates (modified Rankin score ordinal shift analysis) at 3 months after stroke onset.

  3 months

Secondary Outcomes (1)

• Symptomatic intracerebral hemorrhage

  0-24 hours from treatment

Study Arms (2)

Target group

EXPERIMENTAL

A combined treatment with transcranial US and systemic tPA

Device: Transcranial ultrasound as an adjunctive therapy to tPA

Control group

ACTIVE COMPARATOR

Systemic tPA alone

Drug: Standard of care tPA therapy for acute ischemic stroke

Interventions

Transcranial ultrasound as an adjunctive therapy to tPA DEVICE

* tPA per approved labeling administered over 60 minutes * Ultrasonic headframe with active insonation for 120 minutes

Target group

Standard of care tPA therapy for acute ischemic stroke DRUG

* tPA per approved labeling administered over 60 minutes * Ultrasonic headframe with sham (inactive) insonation for 120 minutes

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females 18 - 80 years of age
• Subjects presenting within timeframe for intravenous tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms
• No signs of intracranial bleeding on assessment by non-contrast CT
• Subjects with neurological deficits of a total NIHSS score ≥ 10 points
• Subjects that in the opinion of the treating physician require treatment with full dose IV tPA as standard of care per institutional standards
• SBP \< 185 mmHg and DBP \< 105 mmHg at baseline or after treatment of hypertension with medications prior to tPA bolus
• Pre-morbid modified Rankin score of 0-1
• 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
• 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
• For subjects in the optional arterial recanalization substudy:
• Occlusion located in the intracranial carotid tee through mid M2 or proximal A2, or intracranial vertebrobasilar or P1/proximal P2 segments or tandem lesions
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min for patients undergoing CTA or MRA

You may not qualify if:

• Subjects with primary intra-arterial thrombolysis
• Females who are pregnant or breast feeding
• Subjects receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment
• Subjects with any standard contraindication for intravenous tPA therapy

Sponsors & Collaborators

• Cerevast Therapeutics, Inc.: lead

Study Sites (1)

Cerevast Therapeutics, Inc.

Redmond, Washington, 98052-2431, United States

Location

Related Publications (2)

• Alexandrov AV, Kohrmann M, Soinne L, Tsivgoulis G, Barreto AD, Demchuk AM, Sharma VK, Mikulik R, Muir KW, Brandt G, Alleman J, Grotta JC, Levi CR, Molina CA, Saqqur M, Mavridis D, Psaltopoulou T, Vosko M, Fiebach JB, Mandava P, Kent TA, Alexandrov AW, Schellinger PD; CLOTBUST-ER Trial Investigators. Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Neurol. 2019 Apr;18(4):338-347. doi: 10.1016/S1474-4422(19)30026-2.

  PMID: 30878103 DERIVED

• Schellinger PD, Alexandrov AV, Barreto AD, Demchuk AM, Tsivgoulis G, Kohrmann M, Alleman J, Howard V, Howard G, Alexandrov AW, Brandt G, Molina CA; CLOTBUSTER Investigators. Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial. Int J Stroke. 2015 Oct;10(7):1141-8. doi: 10.1111/ijs.12536. Epub 2015 Jun 29.

  PMID: 26120902 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2010
• First Posted: April 6, 2010
• Study Start: May 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 7, 2015

Record last verified: 2015-04

Locations

US (1)