CLOTBUST Hands-Free: A Phase I/II Pilot Safety Trial

NCT01240356 | Completed Phase 1 Results DMC

• 1 other identifier: CLOTBUST-HF
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of CLOTBUST-HF is to determine the safety of a novel, external Hands-Free transcranial Doppler (TCD) ultrasound system in healthy volunteers and ischemic stroke patients. If found to be safe, the widespread use of operator-independent, ultrasound-enhanced thrombolysis will allow the planning for a large Phase III efficacy trial.

Conditions

Stroke

Keywords

transcranial doppler; sonothrombolysis; ultrasound; stroke

Outcome Measures

Primary Outcomes (3)

• Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain

  Phase I : Imaging of the brain via MRI scans was performed to determine if the Hands-Free transcranial Doppler (TCD) system results in any BBB-disruption or deterioration in permeability.

  2-3 hours after treatment

• Safety in Phase II Group as Measured by Incidence of Symptomatic Intracerebral Hemorrhage

  Phase II: Determine if the Hands-Free TCD will not result in higher than 10% rate of symptomatic intracerebral hemorrhage (ICH) within 24 hours (defined as clinical worsening \> 4 NIH Stroke Scale (NIHSS) points and presence of hemorrhage on CT scan that in the opinion of the treating physician is causatively related to ICH on CT) in 0-3 hours acute stroke patients treated with intravenous tissue-type plasminogen activator (IV-t-PA).

  within 24 hours

• Number of Participants in Phase I Group With Neurological Deterioration as Measured by Neurological Examination

  The neurological examinations comprised assessments of mental status and orientation, cranial nerve examination, muscle strength and tone, deep tendon reflexes, sensory testing, coordination, and gait.

  2-3 hours after treatment

Secondary Outcomes (4)

• Number of Participants in Phase I Group With Adverse Events During and After Study Treatment With HF TCD

  2-3 hours after treatment

• Percentage of Participants in the Phase II Group That Show Arterial Recanalization as Measured Using Standard Transcranial Doppler Ultrasound Systems

  2-3 hours after treatment

• Percentage of Participants in Phase II Group With Neurological Worsening as Determined by the NIH Stroke Scale

  within 90 days of enrollment

• Percentage of Participants in Phase II Group With Excellent Outcome as Measured by Modified Rankin Scale (mRS)

  at 3-months from enrollment

Study Arms (2)

Phase I: Healthy Volunteers

EXPERIMENTAL

Subjects without history of Central Nervous System Disease will receive 2-hours of hands-free 2-megahertz (MHz) transcranial Doppler ultrasound insonation continuously. A brain MRI with gadolinium will be performed before and after the ultrasound.

Device: 2-MHz transcranial Doppler ultrasound

Phase II: 0-3 hour Patients

EXPERIMENTAL

Ischemic stroke patients who present between 0-3 hours will receive 2-hours of hands-free 2-MHz transcranial Doppler ultrasound Continuously to the intracranial vessels.

Device: 2-MHz transcranial Doppler ultrasound insonation

Interventions

2-MHz transcranial Doppler ultrasound DEVICE

2-hours of hands-free ultrasound will be insonated continuously. A brain MRI with gadolinium will be performed before and after the ultrasound.

Also known as: transcranial Doppler Ultrasound, ultrasound

Phase I: Healthy Volunteers

2-MHz transcranial Doppler ultrasound insonation DEVICE

2-hours of hands-free ultrasound delivered to in the intracranial vessels.

Also known as: transcranial Doppler ultrasound, ultrasound, sonothrombolysis

Phase II: 0-3 hour Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase I Safety (healthy volunteers):
• Presence of temporal windows as measured first by an FDA-approved diagnostic TCD device.
• Age ≥ 18 years old.
• Signed informed consent.
• Phase II (0-3 hours ischemic stroke patients):
• Disabling focal neurological deficit (NIHSS \> 4 points);
• No evidence of hemorrhage on non-contrast head CT scan;
• Intravenous rt-PA (0.9 mg/kg, 10% bolus 90% infusion over 1 hour, maximum dose 90 mg) infusion initiated within 3 hours of symptom onset;
• Diagnostic TCD completed and HF-TCD placed before rt-PA bolus.
• Diagnostic TCD confirms intracranial arterial occlusion of the middle cerebral artery (MCA), anterior cerebral artery (ACA), internal carotid artery (ICA), posterior cerebral artery (PCA) or distal basilar artery.
• Age ≥ 18 years old.
• Signed informed consent.
• Phase II (3-6 hours ischemic stroke patients):
• Measurable focal neurological deficit (NIHSS \> 4 points);
• No evidence of hemorrhage on non-contrast head CT scan;

You may not qualify if:

• Phase I Safety (healthy volunteers):
• History of any neurological disease affecting the central nervous system;
• Lack of temporal windows.
• History of renal disease or glomerular filtration rate (GFR) \< 60.
• Contraindication to MRI (e.g., pacemaker, spinal cord stimulator, severe claustrophobia)
• Phase II (0-3 hours ischemic stroke patients):
• Absent temporal windows in patients with anterior circulation ischemia;
• Intra-arterial thrombolysis;
• Patient refusal to give informed consent to participate in the CLOTBUST-HF trial;
• Contraindications for intravenous rt-PA (NINDS rt-PA Stroke Study Protocol)2.
• Phase II (3-6 hours ischemic stroke patients):
• Absent temporal windows in patients with anterior circulation ischemia;
• Intra-arterial thrombolysis;
• Patient refusal to give informed consent to participate in the CLOTBUST-HF trial;
• History of allergic response to Definity® microspheres or microbubbles currently being tested (MRX-801);

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• University of Alabama at Birmingham: collaborator

Study Sites (2)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

UT Medical School-Houston

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Barlinn K, Barreto AD, Sisson A, Liebeskind DS, Schafer ME, Alleman J, Zhao L, Shen L, Cava LF, Rahbar MH, Grotta JC, Alexandrov AV. CLOTBUST-hands free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers. Stroke. 2013 Jun;44(6):1641-6. doi: 10.1161/STROKEAHA.113.001122. Epub 2013 Apr 18.

  PMID: 23598523 RESULT

• Barreto AD, Alexandrov AV, Shen L, Sisson A, Bursaw AW, Sahota P, Peng H, Ardjomand-Hessabi M, Pandurengan R, Rahbar MH, Barlinn K, Indupuru H, Gonzales NR, Savitz SI, Grotta JC. CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke. Stroke. 2013 Dec;44(12):3376-81. doi: 10.1161/STROKEAHA.113.002713. Epub 2013 Oct 24.

  PMID: 24159060 RESULT

• Al-hussain F, Hussain MS, Molina C, Uchino K, Shuaib A, Demchuk AM, Alexandrov AV, Saqqur M; CLOTBUST Investigators. Does the sex of acute stroke patients influence the effectiveness of rt-PA? BMC Neurol. 2014 Mar 26;14:60. doi: 10.1186/1471-2377-14-60.

  PMID: 24669960 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Ultrasonography, Doppler, Transcranial; Ultrasonography

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Echoencephalography; Neuroradiography; Neuroimaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiography; Ultrasonography, Doppler; Diagnostic Techniques, Neurological; Investigative Techniques

Limitations and Caveats

The last phase (Phase II: 3-6 hour non-lytic patients who presented between 3-6 hours and with evidence of mismatch on neuroimaging), was not completed. This portion of the study was not started as new published evidence suggested little value.

Results Point of Contact

• Title: James C. Grotta, MD
• Organization: The University of Texas Health Science Center at Houston

james.c.grotta@uth.tmc.edu

+1 (713) 500-7088

Study Officials

• James C. Grotta, MD

  UT Medical School-Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 8, 2010
• First Posted: November 15, 2010
• Study Start: December 1, 2008
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-05

Locations

US (2)