Trial Outcomes & Findings for CLOTBUST Hands-Free: A Phase I/II Pilot Safety Trial (NCT NCT01240356)

NCT ID: NCT01240356

Last Updated: 2016-05-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: 2-3 hours after treatment
• Results posted on: 2016-05-23

Participant Flow

Participant milestones

Measure	Phase I Non-stroke volunteers.	Phase II Acute Ischemic Stroke patients received standard-doce intravenous tissue-type plasminogen activator (tPA) within 0-3 hours window.
Overall Study STARTED	18	20
Overall Study COMPLETED	15	20
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	Phase I Non-stroke volunteers.	Phase II Acute Ischemic Stroke patients received standard-doce intravenous tissue-type plasminogen activator (tPA) within 0-3 hours window.
Overall Study Withdrawal by Subject	2	0
Overall Study MRI contraindication	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Phase I n=15 Participants Non-stroke volunteers.	Phase II n=20 Participants Phase II-20 patients with ischemic stroke treated with IV-tPA	Total n=35 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	49 years STANDARD_DEVIATION 16 • n=5 Participants	63 years STANDARD_DEVIATION 14 • n=7 Participants	57 years STANDARD_DEVIATION 17 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	20 participants n=7 Participants	35 participants n=5 Participants

PRIMARY outcome

Timeframe: 2-3 hours after treatment

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.

Outcome measures

Measure	Phase I n=15 Participants Non stroke patients
Number of Participants in Phase I Group With Blood-brain-barrier Disruption (BBB) as Measured by MRI of the Brain	0 participants

PRIMARY outcome

Timeframe: within 24 hours

Population: Intention to Treat (ITT)

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).

Outcome measures

Measure	Phase I n=20 Participants Non stroke patients
Safety in Phase II Group as Measured by Incidence of Symptomatic Intracerebral Hemorrhage	0 percentage of patients Interval 0.0 to 17.0

PRIMARY outcome

Timeframe: 2-3 hours after treatment

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.

Outcome measures

Measure	Phase I n=15 Participants Non stroke patients
Number of Participants in Phase I Group With Neurological Deterioration as Measured by Neurological Examination	0 participants

SECONDARY outcome

Timeframe: 2-3 hours after treatment

Population: ITT

Phase I - A group of healthy volunteers will be assessed to determine the feasibility and activity of hands-free (HF) transcranial Doppler (TCD). Adverse events include subject complaints regarding discomfort of the device and dermatological adverse events as evidenced by a detailed physical examination of skin integrity post-insonation.

Outcome measures

Measure	Phase I n=15 Participants Non stroke patients
Number of Participants in Phase I Group With Adverse Events During and After Study Treatment With HF TCD	0 participants

SECONDARY outcome

Timeframe: 2-3 hours after treatment

Population: ITT - Percent of patients who had complete recanalization after treatment.

Ischemic stroke patients: 2-hour rates of arterial complete and partial recanalization as measured using standard Transcranial Doppler Ultrasound systems.

Outcome measures

Measure	Phase I n=20 Participants Non stroke patients
Percentage of Participants in the Phase II Group That Show Arterial Recanalization as Measured Using Standard Transcranial Doppler Ultrasound Systems	40 percentage of patients Interval 19.0 to 64.0

SECONDARY outcome

Timeframe: within 90 days of enrollment

The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. Each item on the NIHSS scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.

Outcome measures

Measure	Phase I n=20 Participants Non stroke patients
Percentage of Participants in Phase II Group With Neurological Worsening as Determined by the NIH Stroke Scale	5 percentage of patients Interval 0.0 to 25.0

SECONDARY outcome

Timeframe: at 3-months from enrollment

Population: ITT with modified Ranking scores (mSR) at 90 days. % displayed is % with excellent outcome (mRS of 0-1).

A modified Rankin Scale (mRS) score of 0 or 1 indicates an excellent outcome. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS scale ranks patients from 0 to 6 (0 is the best score, 6 is the worst score).

Outcome measures

Measure	Phase I n=20 Participants Non stroke patients
Percentage of Participants in Phase II Group With Excellent Outcome as Measured by Modified Rankin Scale (mRS)	25 percentage of patients Interval 7.0 to 49.0

Adverse Events

Phase I: Healthy Volunteers

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase II - Ischemic Stroke Patients

Serious events: 9 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase I: Healthy Volunteers n=15 participants at risk Phase I - 15 non-stroke healthy volunteers.	Phase II - Ischemic Stroke Patients n=20 participants at risk Phase II - 20 patient with ischemic stroke treated with IV-tPA
Nervous system disorders Intracranial hemohhrage secondary to bacterial endocarditis	0.00% 0/15	5.0% 1/20 • Number of events 1
Nervous system disorders Death	0.00% 0/15	15.0% 3/20 • Number of events 3
Nervous system disorders Cerebral edema	0.00% 0/15	20.0% 4/20 • Number of events 4
Respiratory, thoracic and mediastinal disorders Pneumonia/respiratory failure	0.00% 0/15	20.0% 4/20 • Number of events 4
Infections and infestations Sepsis	0.00% 0/15	5.0% 1/20 • Number of events 1
Nervous system disorders Stroke progression/Nuero-worsening	0.00% 0/15	5.0% 1/20 • Number of events 1

Other adverse events

Measure	Phase I: Healthy Volunteers n=15 participants at risk Phase I - 15 non-stroke healthy volunteers.	Phase II - Ischemic Stroke Patients n=20 participants at risk Phase II - 20 patient with ischemic stroke treated with IV-tPA
Infections and infestations Fewer	0.00% 0/15	30.0% 6/20 • Number of events 6
Blood and lymphatic system disorders Anemia/decreased hemoglobin and hematocrit	0.00% 0/15	30.0% 6/20 • Number of events 6
Cardiac disorders Hypertension	0.00% 0/15	30.0% 6/20 • Number of events 6
Cardiac disorders Hypotension	0.00% 0/15	5.0% 1/20 • Number of events 1
Blood and lymphatic system disorders Electrolyze imbalance	0.00% 0/15	5.0% 1/20 • Number of events 1
Cardiac disorders Bradycardia	0.00% 0/15	10.0% 2/20 • Number of events 2
Cardiac disorders Tachycardia	0.00% 0/15	20.0% 4/20 • Number of events 4
Respiratory, thoracic and mediastinal disorders Tachypnea	0.00% 0/15	20.0% 4/20 • Number of events 4
Respiratory, thoracic and mediastinal disorders Right lung atelectasis	0.00% 0/15	5.0% 1/20 • Number of events 1
Cardiac disorders Elevated CK	0.00% 0/15	5.0% 1/20 • Number of events 1
Infections and infestations Elevated white blood count	0.00% 0/15	25.0% 5/20 • Number of events 5
Infections and infestations Utinary tract infection	0.00% 0/15	10.0% 2/20 • Number of events 2
Nervous system disorders Asymptomatic ICH	0.00% 0/15	30.0% 6/20 • Number of events 6
Nervous system disorders Elevated Coag lab test	0.00% 0/15	5.0% 1/20 • Number of events 1
Cardiac disorders New diagnosis of PFO	0.00% 0/15	5.0% 1/20 • Number of events 1
Renal and urinary disorders Elevated Creatinine	0.00% 0/15	5.0% 1/20 • Number of events 1
Respiratory, thoracic and mediastinal disorders Positive sputum culture	0.00% 0/15	5.0% 1/20 • Number of events 1

Additional Information

James C. Grotta, MD

The University of Texas Health Science Center at Houston

Phone: +1 (713) 500-7088

Email: james.c.grotta@uth.tmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place