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)

Cerevast Therapeutics

Status and phase: Terminated; Phase 3

Conditions: Acute Ischemic Stroke

Treatments: Drug: Standard of care tPA therapy for acute ischemic stroke; Device: Transcranial ultrasound as an adjunctive therapy to tPA

Study type: Interventional

Funder types: Industry

Identifiers

NCT01098981

CEREVAST THERAPEUTICS CP-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 675 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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675 participants in 2 patient groups

Target group

Experimental group

Description:

A combined treatment with transcranial US and systemic tPA

Treatment:

Device: Transcranial ultrasound as an adjunctive therapy to tPA

Control group

Active Comparator group

Description:

Systemic tPA alone

Treatment:

Drug: Standard of care tPA therapy for acute ischemic stroke