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

Completed

Phase 1/2 Results

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)
1. CT-perfusion
- ≥ 20% difference between affected territories on Time to Peak (TTP) and Cerebral Blood Volume (CBV) maps.
2. 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) < 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);
- Baseline imaging consistent with a malignant ischemic pattern (low CBV values or DWI territory >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.