A Phase II, randomized, blinded, placebo-controlled, parallel group study with patients experiencing a large vessel occlusion acute ischemic stroke who are selected for endovascular revascularization. Participants will be given a 48 h infusion of either 0.5 mL/kg/h RNS60 (up to a maximum of 65 mL/h), 1.0 mL/kg/h RNS60 (up to a maximum of 130 mL/h), or 1.0 mL/kg/h (up to a maximum of 130 mL/h) placebo (normal saline) starting within 30 minutes of consent after confirmation of candidacy for endovascular thrombectomy.
This study is a Phase II, randomized, blinded, placebo-controlled, parallel group design. Participants experiencing a large vessel occlusion acute ischemic stroke who are selected for endovascular revascularization will be given a 48 h infusion of either 0.5 mL/kg/h RNS60 (up to a maximum of 65 mL/h), 1.0 mL/kg/h RNS60 (up to a maximum of 130 mL/h), or 1.0 mL/kg/h (up to a maximum of 130 mL/h) placebo (normal saline) starting within 30 minutes of consent after confirmation of candidacy for endovascular thrombectomy and prior to arterial closure. Outcomes of the main trial will be evaluated throughout a 90 day observation period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
83
Northwestern University
Chicago, Illinois, United States
Oregon Health & Science University
Portland, Oregon, United States
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Number of Participants With Serious Adverse Events (SAEs)
An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in a congenital anomaly/birth defect. An SAE could also be an important medical event that may not have resulted in death, was life-threatening, or required hospitalization, but jeopardized the participant and required medical or surgical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs that started after the start of study drug infusion and are reported here.
Time frame: From start of study drug administration up to Day 90
Mortality: Proportion of Participants Alive at Day 90
Time frame: Day 90
Number of Participants With Non-disability Based on Modified Rankin Scale (mRS ) Score at Day 90
The mRS is a clinician-reported outcome measure for participants who have suffered a stroke. It measures functional recovery as the degree of disability or dependence in daily activities in a 6-point disability scale with possible scores ranging from 0 to 5: 0-no symptoms at all; 1-no significant disability despite symptoms; able to carry out all usual duties and activities; 2-slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3-moderate disability: requiring some help, but able to walk without assistance; 4-moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs without assistance; 5-severe disability; bedridden, incontinent, requiring constant nursing care and attention. A score of 6 is used for participants who expire (death). Non-disability was defined as a score ranging from 0 to 2. Disability was defined as a score ranging from 3-6.
Time frame: Day 90
Change From Baseline in Infarct Volume of Stroke at 48 Hours
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Rhode Island Hospital
Providence, Rhode Island, United States
Chattanooga Center for Neurologic Research
Chattanooga, Tennessee, United States
Houston Methodist Hospital
Houston, Texas, United States
Infarct progression/regression was measured by Magnetic Resonance Imaging (MRI) of the brain. The mean change from post-EVT baseline in the volume of injured tissue was calculated at 48 hours.
Time frame: Baseline, 48 hours
National Institutes of Health Stroke Scale (NIHSS) at 24 Hours
The NIHSS is a standardized neurological examination scale that is a measure of disability and recovery after acute stroke. The NIHSS assessment is a standardized 15-item impairment scale intended to evaluate neurologic outcome and degrees of recovery for subjects with stroke. The scale assesses levels of consciousness, extraocular movements, visual fields, facial muscle function, extremity strength, sensory function, coordination (ataxia), language (aphasia), speech (dysarthria), and hemi-inattention (neglect). The NIHSS was scored by those trained in the use of this scale. Each item was scored in ranges 0-2, 0-3, or 0-4. A score of 0 indicates normal performance. Total scores on the NIHSS ranged from 0-42, with higher values reflecting increasing severity. Stroke severity was further stratified in the following way: \> 25: Very severe; 15-24: Severe; 5-14: Mild to moderately severe; \< 5: Mild.
Time frame: 24 hours
Proportion of Participants With Worsening of Stroke
Worsening of stroke was defined as progression, or hemorrhagic transformation of the index stroke, as documented by brain imaging, which is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥ 4-point increase from lowest NIHSS pre-decline and/or (c) results in death. Proportion of participants with worsening of stroke was calculated as number of participants with worsening of stroke divided by the total number of participants observed over the 90-day period in each arm.
Time frame: Up to Day 90
Percentage of Participants With Barthel Index (BI) Score ≥95 at Day 90
The BI is an index of functional independence. Its values range from 0 to 100, with higher scores indicating greater independence. Score range in BI items: Feeding 0-10; Bathing 0-5; Grooming 0-5; Dressing 0-10; Bowels 0-10; Bladder 0-10; Toilet use 0-10; Transfers (bed to chair and back) 0-15; Mobility (on level surfaces) 0-15; Stairs 0-10. Item scores vary in increments of 5 points. Functional independence at Day 90 was evaluated. Participants having a score ≥95 on the BI Score were deemed to have achieved functional independence, whereas those scoring \<95 at Day 90 were deemed to have failed to achieve functional independence.
Time frame: Day 90
Health-related Quality of Life as Measured by 5-Level EuroQoL 5D Index (EQ-5D-5L) at Day 90
EQ-5D-5L is a generic instrument for measuring health-related quality of life. It consists of a 5-item questionnaire, which was interviewer administered by study staff. The 5-item questionnaire comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and each dimension has 5 response levels (1-no problems, 2-slight problems, 3-moderate problems, 4-severe problems, 5-unable to/extreme problems). The health state is then summarized to be a single number, EQ-5D-5L Index score, by applying a country-specific standard value set. EQ-5D-5L Index score for the United States ranges from -0.59 to 1, where 1 indicates a better health condition.
Time frame: Day 90