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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 (CLOTBUST-ER)

Primary Purpose

Acute Ischemic Stroke

Status

Terminated

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Transcranial ultrasound as an adjunctive therapy to tPA

Standard of care tPA therapy for acute ischemic stroke

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
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:

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
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

Sites / Locations

Cerevast Therapeutics, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Target group

Control group

Arm Description

A combined treatment with transcranial US and systemic tPA

Systemic tPA alone

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Symptomatic intracerebral hemorrhage

The secondary outcome is a comparison of the rates of symptomatic intracerebral hemorrhage within 0-24 hours from initiation of treatment.

Full Information

NCT ID

NCT01098981

First Posted

April 2, 2010

Last Updated

April 3, 2015

Sponsor

Cerevast Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01098981

Brief Title

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

Acronym

CLOTBUST-ER

Official Title

A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of the Combined Lysis of Thrombus With Ultrasound and Systemic Tissue Plasminogen Activator (tPA) for Emergent Revascularization (CLOTBUST-ER) in Acute Ischemic Stroke

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Terminated

Study Start Date

May 2013 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cerevast Therapeutics, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Ischemic Stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

675 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Target group

Arm Type

Experimental

Arm Description

A combined treatment with transcranial US and systemic tPA

Arm Title

Control group

Arm Type

Active Comparator

Arm Description

Systemic tPA alone

Intervention Type

Device

Intervention Name(s)

Transcranial ultrasound as an adjunctive therapy to tPA

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Standard of care tPA therapy for acute ischemic stroke

Intervention Description

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

Primary Outcome Measure Information:

Title

Modified Rankin score ordinal shift analysis

Description

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

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Symptomatic intracerebral hemorrhage

Description

The secondary outcome is a comparison of the rates of symptomatic intracerebral hemorrhage within 0-24 hours from initiation of treatment.

Time Frame

0-24 hours from treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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

Facility Information:

Facility Name

Cerevast Therapeutics, Inc.

City

Redmond

State/Province

Washington

ZIP/Postal Code

98052-2431

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

30878103

Citation

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.

Results Reference

derived

PubMed Identifier

26120902

Citation

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.

Results Reference

derived

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