Clinical trial NCT01811693: Field Administration of Stroke Therapy-Blood Pressure Lowering
Official title: The Field Administration of Stroke Therapy-Blood Pressure Lowering Pilot Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Ischemic Stroke
Keywords: Stroke
Intracerebral Hemorrhage
Prehospital
Antihypertensive
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2013-03-14
Enrollment: 4
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Participants With Systolic Blood Pressure Change of 8mmHg or More
timeFrame: Baseline, 15 minutes after treatment
Secondary outcomes:
Other outcomes:
measure: Participants Experiencing Serious Adverse Events
timeFrame: 90 days after enrollment
measure: Participants Exhibiting Neurological Deterioration as Indicated by a Two-point or Greater Worsening in the Glasgow Coma Scale
timeFrame: Baseline, One hour after enrollment
measure: Participants With Systolic Blood Pressure Less Than 120 mm/Hg
timeFrame: 24 hours after enrollment
Locations:
city: Los Alamitos
country: United States
facility: Los Alamitos Medical Center
state: California
city: Los Angeles
country: United States
facility: FAST-MAG Clinical Trial Coordinating Center
state: California
Study officials:
References: