FAST-BP: Field Administration of Stroke Therapy-Blood Pressure Lowering

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01811693
• Collaborator: (none)
• Enrollment: 4
• Locations: 2
• Arms: 3
• Duration (Months): 8.3
• Patients Per Site: 2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage; Ischemic Stroke	Drug: Glycerly Trinitrate; Drug: Glycerly Trinitrate; Drug: Glycerly Trinitrate	Phase 2

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.

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Field Administration of Stroke Therapy-Blood Pressure Lowering Pilot Trial
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Sep 10, 2013
• Actual Study Completion Date: Dec 9, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Tier 1 Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal	Drug: Glycerly Trinitrate; 5mg/24hour (0.2mg/hour) transdermal; Other Names: Nitroglycerine GTN
Experimental: Dose Tier 2 Glycerly Trinitrate (Nitroglycerine) 10mg/24hour (0.4mg/hour) transdermal	Drug: Glycerly Trinitrate; 10mg/24hour (0.4mg/hour) transdermal; Other Names: Nitroglycerine GTN
Experimental: Dose Tier 3 Glycerly Trinitrate (GTN, Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal plus a single metered dose 0.4mg of sublingual GTN	Drug: Glycerly Trinitrate; 10mg/24hour (0.4mg/hour) transdermal; Other Names: Nitroglycerine GTN ; Drug: Glycerly Trinitrate; 0.4 mg sublingual single metered spray; Other Names: Nitroglycerine GTN

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Participants Experiencing Serious Adverse Events [90 days after enrollment]

2. 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.

3. Participants With Systolic Blood Pressure Less Than 120 mm/Hg [24 hours after enrollment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Alamitos Medical Center	Los Alamitos	California	United States	90720
2	FAST-MAG Clinical Trial Coordinating Center	Los Angeles	California	United States	90024

Sponsors and Collaborators

• University of California, Los Angeles

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey L. Saver, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01811693
• Other Study ID Numbers: FBP001
• First Posted: Mar 14, 2013
• Last Update Posted: Oct 29, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Jeffrey L. Saver, Principal Investigator, University of California, Los Angeles: Stroke; Intracerebral Hemorrhage; Prehospital; Antihypertensive
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Cerebral Hemorrhage; Hemorrhage; Nitroglycerin

Study Results

Participant Flow

Arm/Group Title	Dose Tier 1	Dose Tier 2	Dose Tier 3
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal	Glycerly Trinitrate (Nitroglycerine) 10mg/24hour (0.4mg/hour) transdermal Glycerly Trinitrate: 10mg/24hour (0.4mg/hour) transdermal	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
Period Title: Overall Study
STARTED	4	0	0
COMPLETED	4	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Tier 1	Dose Tier 2	Dose Tier 3	Total
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal	Glycerly Trinitrate (Nitroglycerine) 10mg/24hour (0.4mg/hour) transdermal Glycerly Trinitrate: 10mg/24hour (0.4mg/hour) transdermal	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	Total of all reporting groups
Overall Participants	4	0	0	4
Age (Count of Participants)
<=18 years	0 0%	0 NaN	0 NaN	0 0%
Between 18 and 65 years	2 50%	0 NaN	0 NaN	2 50%
>=65 years	2 50%	0 NaN	0 NaN	2 50%
Sex: Female, Male (Count of Participants)
Female	2 50%	0 NaN	0 NaN	2 50%
Male	2 50%	0 NaN	0 NaN	2 50%

Outcome Measures

1. Primary Outcome

Title	Participants With Systolic Blood Pressure Change of 8mmHg or More
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Tier 1
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal
Measure Participants	4
Count of Participants [Participants]	1 25%

2. Other Pre-specified Outcome

Title	Participants Experiencing Serious Adverse Events
Time Frame	90 days after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Tier 1
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal
Measure Participants	4
SAE	2 50%
No SAE	2 50%

3. Other Pre-specified Outcome

Title	Participants Exhibiting Neurological Deterioration as Indicated by a Two-point or Greater Worsening in the Glasgow Coma Scale
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Tier 1
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal
Measure Participants	4
Count of Participants [Participants]	1 25%

4. Other Pre-specified Outcome

Title	Participants With Systolic Blood Pressure Less Than 120 mm/Hg
Time Frame	24 hours after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Tier 1
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal
Measure Participants	4
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	90 days after enrollment
Arm/Group Title	Dose Tier 1
Arm/Group Description	Glycerly Trinitrate (Nitroglycerine) 5mg/24hour (0.2mg/hour) transdermal Glycerly Trinitrate: 5mg/24hour (0.2mg/hour) transdermal
All Cause Mortality
	Dose Tier 1
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dose Tier 1
	Affected / at Risk (%)	# Events
Total	2/4 (50%)
Vascular disorders
Death	2/4 (50%)	2
Other (Not Including Serious) Adverse Events
	Dose Tier 1
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.