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

NCT ID: NCT01098981

Last Updated: 2015-04-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 675 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2015-04-30

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.

Detailed Description

The primary objective of this trial is to provide information regarding the efficacy of a combined treatment with transcranial US and systemic tPA (Target group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke. The primary efficacy endpoint is functional outcome at 3 months from stroke onset (modified Rankin Score ordinal shift analysis). The primary safety endpoint is the proportion of subjects in the Target vs Control group experiencing symptomatic intracranial hemorrhage (sICH) within 24 hours of treatment.

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Target group

A combined treatment with transcranial US and systemic tPA

Group Type: EXPERIMENTAL

Transcranial ultrasound as an adjunctive therapy to tPA

Intervention Type: DEVICE

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

Control group

Systemic tPA alone

Group Type: ACTIVE_COMPARATOR

Standard of care tPA therapy for acute ischemic stroke

Intervention Type: DRUG

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

Interventions

Transcranial ultrasound as an adjunctive therapy to tPA

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

Intervention Type: DEVICE

Standard of care tPA therapy for acute ischemic stroke

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Males or females 18 - 80 years of age

2. Subjects presenting within timeframe for intravenous tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms

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

4. Subjects with neurological deficits of a total NIHSS score ≥ 10 points

5. Subjects that in the opinion of the treating physician require treatment with full dose IV tPA as standard of care per institutional standards

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

7. Pre-morbid modified Rankin score of 0-1

8. 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

9. 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

10. For subjects in the optional arterial recanalization substudy:

1. Occlusion located in the intracranial carotid tee through mid M2 or proximal A2, or intracranial vertebrobasilar or P1/proximal P2 segments or tandem lesions

2. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min for patients undergoing CTA or MRA

Exclusion Criteria

1. Subjects with primary intra-arterial thrombolysis

2. Females who are pregnant or breast feeding

3. Subjects receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment

4. Subjects with any standard contraindication for intravenous tPA therapy

5. Significant concurrent medical/neurological conditions or test values that, in the opinion of the investigator, pose significant risk to the subject and warrant exclusion from the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cerevast Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cerevast Therapeutics, Inc.

Redmond, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30878103 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26120902 (View on PubMed)

Other Identifiers

CEREVAST THERAPEUTICS CP-01

Identifier Type: -

Identifier Source: org_study_id