Intracerebral Hemorrhage, Ischemic Stroke
Conditions
Keywords
Stroke, Intracerebral Hemorrhage, Prehospital, Antihypertensive
Brief summary
This is an open, pilot, dose-escalation study of glyceryl trinitrate (GTN, Nitroglycerin) administered by paramedics in the field within 2 hours of symptom onset to 45 severely hypertensive stroke patients. The primary objective of the study is to evaluate the feasibility, safety, and physiologic efficacy of field-initiated glyceryl trinitrate in achieving modest reduction of blood pressure. Patients with acute stroke will be identified in the field by paramedics who have received training in basic and advanced cardiac life support, stroke recognition, and specific procedures relevant to the proposed study. Physician-investigators will obtain informed consent for each subject for study entry after cellular phone contact with paramedics. Paramedics will initiate antihypertensive treatment by applying transdermal GTN patch in the first two dose-tiers, and administering a single sublingual GTN metered spray followed by application of the transdermal system in the last dose tier. The sites involved in the study will be emergency medical services rescue ambulances and 8 receiving Stroke Center hospitals in Orange County, California, USA.
Detailed description
The central aim of this phase 2a study is to identify a regimen of paramedic initiated glyceryl trinitrate antihypertensive therapy in acute stroke patients that is safe, is technically effective in modestly lowering blood pressure, and is optimal to advance to a pivotal trial. The study design is an open-label dose escalation study with three dose tiers,. It is anticipated that the trial will identify the most promising prehospital GTN regimen to advance to a pivotal, placebo-controlled, phase 3 trial. Primary Hypothesis: Prehospital glyceryl trinitrate treatment reduces severely hypertensive blood pressure elevation by ED arrival. The primary study endpoint to test this hypothesis will be the mean change in SBP from pre-treatment to ED arrival. Secondary Hypotheses: 1. Prehospital glyceryl trinitrate treatment reduces severely hypertensive blood pressure elevation at early post-arrival timepoints and increases the proportion of patients with target blood pressure at ED arrival and early post-arrival timepoints. The secondary study endpoints analyzed to test these hypotheses will be: 1) mean change in SBP from pre-treatment to 30 minutes after ED arrival and 60 minutes after ED arrival; and 2) the proportion of patients with SBP \< 180 mm Hg at ED arrival, 30, and 60 minutes after arrival. 2. Prehospital initiation of glyceryl trinitrate in the first 2 hours for severely hypertensive patients with stroke is feasible and safe. Safety of GTN in the first 2 hours for severely hypertensive stroke patients will be assessed by analysis of serious adverse events, neurologic change, and mortality. We hypothesize that initiation of treatment of the patients in the field will be associated with a favorable side effect profile and without severe blood pressure lowering to les than 120 mm Hg systolic. Successful completion of the study will demonstrate feasibility to recruit hypertensive stroke participants and initiate GTN therapy in the field by paramedics.
Interventions
DRUGGlycerly Trinitrate
5mg/24hour (0.2mg/hour) transdermal
Sponsors
University of California, Los Angeles
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Suspected stroke identified with Los Angeles Prehospital Stroke Screen 2. Age 40-80, inclusive 3. Last known well time within 2 hours of treatment initiation 4. Deficit present for \> 15 minutes 5. Systolic blood pressure ≥180
Exclusion criteria
1. Coma 2. Rapidly improving neurologic deficit 3. Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound the neurological or functional outcome evaluations 4. Severe respiratory distress (O2 sat \< 90% or respiratory rate \< 12 or \> 24) 5. Major head trauma in the last 24 hours 6. Recent stroke within prior 30 days 7. Use of erectile dysfunction therapies in the previous 12 hours 8. Use of type V phosphodiesterase inhibitors 9. Patient unable to give informed consent and no available legally authorized representative (LAR) to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Systolic Blood Pressure Change of 8mmHg or More | Baseline, 15 minutes after treatment | The mean change in blood pressure was measured in the Emergency Department approximately 15 minutes after application of the treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participants Experiencing Serious Adverse Events | 90 days after enrollment | — |
| Participants Exhibiting Neurological Deterioration as Indicated by a Two-point or Greater Worsening in the Glasgow Coma Scale | Baseline, One hour after enrollment | The Glasgow Coma Scale (GCS) score measures level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired. |
| Participants With Systolic Blood Pressure Less Than 120 mm/Hg | 24 hours after enrollment | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Tier 1 Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal
Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal | 4 |
| Dose Tier 2 Glycerly Trinitrate (Nitroglycerine) 10mg/24hour (0.4mg/hour) transdermal
Glycerly Trinitrate: 10mg/24hour (0.4mg/hour) transdermal | 0 |
| Dose Tier 3 Glycerly Trinitrate (GTN, Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal plus a single metered dose 0.4mg of sublingual GTN
Glycerly Trinitrate: 10mg/24hour (0.4mg/hour) transdermal
Glycerly Trinitrate: 0.4 mg sublingual single metered spray | 0 |
| Total | 4 |
Baseline characteristics
| Characteristic | Dose Tier 1 | Dose Tier 2 | Dose Tier 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Participants With Systolic Blood Pressure Change of 8mmHg or More
The mean change in blood pressure was measured in the Emergency Department approximately 15 minutes after application of the treatment
Time frame: Baseline, 15 minutes after treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Tier 1 | Participants With Systolic Blood Pressure Change of 8mmHg or More | 1 Participants |
Other Pre-specified
Participants Exhibiting Neurological Deterioration as Indicated by a Two-point or Greater Worsening in the Glasgow Coma Scale
The Glasgow Coma Scale (GCS) score measures level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired.
Time frame: Baseline, One hour after enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Tier 1 | Participants Exhibiting Neurological Deterioration as Indicated by a Two-point or Greater Worsening in the Glasgow Coma Scale | 1 Participants |
Other Pre-specified
Participants Experiencing Serious Adverse Events
Time frame: 90 days after enrollment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Tier 1 | Participants Experiencing Serious Adverse Events | SAE | 2 Participants |
| Dose Tier 1 | Participants Experiencing Serious Adverse Events | No SAE | 2 Participants |
Other Pre-specified
Participants With Systolic Blood Pressure Less Than 120 mm/Hg
Time frame: 24 hours after enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Tier 1 | Participants With Systolic Blood Pressure Less Than 120 mm/Hg | 0 Participants |