Stroke, Acute
Conditions
Brief summary
This study will assess the potential efficacy and safety of TSC as early treatment for both ischemic and hemorrhagic stroke when administered while subject is in ambulance being transported to hospital.
Detailed description
This is a multicenter, randomized, placebo-controlled, double-blind, parallel group trial of intravenous trans sodium crocetinate (TSC) initiated by emergency medical service (EMS) responders in the field within 2 hours of symptom onset in 160 subjects with acute stroke. The primary objectives of the study are to evaluate the efficacy and safety of field-initiated TSC in improving the long-term functional outcome of subjects with acute stroke. Subjects with acute stroke will be identified and screened in the ambulance by (EMS) responders who have received training in basic and advanced cardiac life support, stroke recognition, and specific procedures relevant to the proposed study. The EMS responders will contact a Study Neurologist, who will enroll eligible stroke patients into the study. Effort will be made to obtain prospective informed consent in the ambulance when deemed to be feasible. If not feasible, subjects will be enrolled under regulations for exception from explicit informed consent (EFIC) in emergency research circumstances, after public disclosure and community consultation. Written informed consent to continue in the study is obtained from subjects or their legally authorized representatives as soon as possible after hospital arrival. EMS responders will deliver the single, field, bolus dose of study agent, TSC at 0.25 mg/kg or matched placebo, followed after hospital arrival by standard of care (SOC). No additional study drug will be administered in the hospital. Follow-up assessments will be performed at Emergency Department (ED) arrival, 24 hours, 48 hours, Day 4, Day 30, and Day 90. The study will be performed at up to 30 receiving hospital sites in Los Angeles County, CA, and central Virginia.
Interventions
In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.
OTHERPlacebo
The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.
Sponsors
University of California, Los Angeles
University of Virginia
Diffusion Pharmaceuticals Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
TSC injections will be prepared and injected by unblinded personnel on each ambulance. All other study personnel will be blinded
Intervention model description
Multicenter, randomized, placebo-controlled, double-blind, parallel group
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Age 40-85, inclusive 2. Last known well time 15-120 minutes before anticipated study drug injection 3. Suspected stroke identified by the LAPSS 4. Moderate to severe motor deficit, with Los Angeles Motor Scale (LAMS) 2 or higher 5. No seizure
Exclusion criteria
1. Coma 2. Rapidly improving neurologic deficit 3. History of seizures or epilepsy 4. Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound the neurological or functional outcome evaluations 5. SBP \< 90 or \> 220 6. Major head trauma in the last 24 hours 7. Recent stroke within 30 days 8. Known to be pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Disability Level on the Modified Rankin Score (mRS) | 90 days | Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes. 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 and requiring constant nursing care and attention 6. = Dead |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trans Sodium Crocetinate Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.
Trans-Sodium Crocetinate: In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance. | 2 |
| Placebo The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.
Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance. | 4 |
| Total | 6 |
Baseline characteristics
| Characteristic | Trans Sodium Crocetinate | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 74.0 years | 67.2 years | 63.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment United States | 2 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 1 / 4 |
| other Total, other adverse events | 1 / 2 | 4 / 4 |
| serious Total, serious adverse events | 1 / 2 | 2 / 4 |
Outcome results
Primary
Global Disability Level on the Modified Rankin Score (mRS)
Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes. 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 and requiring constant nursing care and attention 6. = Dead
Time frame: 90 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trans Sodium Crocetinate | Global Disability Level on the Modified Rankin Score (mRS) | 2.5 score on a scale |
| Placebo | Global Disability Level on the Modified Rankin Score (mRS) | 3.0 score on a scale |