Phase 2
N=38
CLOTBUST Hands-Free: A Phase I/II Pilot Safety Trial
Stroke
Bottom Line
View on ClinicalTrials.gov: NCT01240356 ↗Enrolled (actual)
38
Serious AEs
25.7%
Results posted
May 2016
Primary outcome: Primary: Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain — 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- 2-MHz transcranial Doppler ultrasound (Device); 2-MHz transcranial Doppler ultrasound insonation (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- The University of Texas Health Science Center, Houston
- Primary completion
- Oct 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain |
— | — |
| PRIMARY Safety in Phase II Group as Measured by Incidence of Symptomatic Intracerebral Hemorrhage |
— | — |
| PRIMARY Number of Participants in Phase I Group With Neurological Deterioration as Measured by Neurological Examination |
— | — |
| SECONDARY Number of Participants in Phase I Group With Adverse Events During and After Study Treatment With HF TCD |
— | — |
| SECONDARY Percentage of Participants in the Phase II Group That Show Arterial Recanalization as Measured Using Standard Transcranial Doppler Ultrasound Systems |
40 | — |
| SECONDARY Percentage of Participants in Phase II Group With Neurological Worsening as Determined by the NIH Stroke Scale |
5 | — |
| SECONDARY Percentage of Participants in Phase II Group With Excellent Outcome as Measured by Modified Rankin Scale (mRS) |
25 | — |
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.
Eligibility Criteria
INCLUSION CRITERIA
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;
- 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.
- Presence of neuroimaging defined mismatch (CT or MRI prior to enrollment)
- CT-perfusion
- ≥ 20% difference between affected territories on Time to Peak (TTP) and Cerebral Blood Volume (CBV) maps.
- MRI Diffusion-Perfusion mismatch
- ≥ 20% difference between diffusion-weighted imaging (DWI) lesion and territory of perfusion delay perfusion weighted imaging (PWI).
- Age ≥ 18 years old.
- Signed informed consent.
EXCLUSION CRITERIA
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) 100cc of tissue);
- Baseline MRI imaging demonstrating delayed perfusion of > 8 seconds in >100cc of brain parenchyma26;
- Patients receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment;
- Significant concurrent medical/neurological conditions or deviation from normal laboratory test values at baseline that, in the opinion of the investigator, pose significant risk to the patient and warrant exclusion from the study;
- Known severe chronic obstructive pulmonary disease (COPD) (baseline oxygen saturation < 80% on room air);
- Known right-to-left cardiac shunt.
Data sourced from ClinicalTrials.gov (NCT01240356). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.