Blood Pressure Lowering in Acute Stroke Trial (BLAST)
|First Received Date ICMJE||July 20, 2011|
|Last Updated Date||July 21, 2011|
|Start Date ICMJE||August 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01400256 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Blood Pressure Lowering in Acute Stroke Trial|
|Official Title ICMJE||The Use of Valsartan for the Management of Blood Pressure in Acute Stroke: Affects on Cerebral Blood Flow|
The investigators hope to show that valsartan can be used safely in the setting of acute stroke to lower elevated blood pressure. There are novel properties of this class of drug (an angiotensive-receptor blocker or ARB), and promising human and animal data, that would suggest this drug can be safely used to lower blood pressure in the setting of acute stroke without compromising brain blood flow (i.e. cerebral perfusion). If this is proved to be the case, this compound could potentially be used routinely in this setting, with the hope of improving outcome. This pilot study may pave the way for a larger randomized trial looking at outcome measures in stroke patients. Further, a positive result in the this pilot study will serve as proof of concept that ARBs maintain cerebral perfusion while decreasing blood pressure, an overall favorable property.
Patients who are suffering from a stroke often present to the hospital with elevated blood pressure. Elevated blood pressure in the setting of stroke increases the risk of brain swelling or bleeding into the brain. Even so, there has been concern about lowering the blood pressure with medications because the newly injured parts of the brain may not get the blood flow they need, thereby worsening the damage from the initial stroke. We hope to demonstrate that the drug valsartan can be used to safely and modestly lower blood pressure in acute stroke patients, without having a detrimental effect on brain blood flow or neurologic status. Novel MRI techniques to measure brain blood flow will be used in conjunction with clinical scales to demonstrate safety.
We intend to enroll 20 patients (10 for active drug, 10 for placebo) over an 16 month period. Patients admitted with the diagnosis of acute stroke and hypertension will be eligible for the study. All patients will be screened by the attending physician on the Stroke Service. Informed consent will be obtained from the patient or a suitable surrogate. Baseline characteristics will be recorded including demographics, drug allergies, date and time of presumed stroke, prior stroke history, history of hypertension, current blood pressure regimen, other cardiovascular risk factors, baseline physical exam, National Institute of Health Stroke Scale (NIHSS) score, and baseline modified Rankin score. Patients will be treated and examined daily by neurologists from the Stroke Service and/or Neurocritical Care teams.
A sustained mean arterial pressure (MAP) of 110 (~150/90) or greater is needed for inclusion in the study. Upon admission, as per our usual protocol, antihypertensive medications will be withheld. In general, we do not administer antihypertensive agents to acute ischemic stroke patients unless the blood pressure is greater than ~200/110 (MAP 140) or the patient has signs or symptoms thought to be secondary to elevated blood pressure. Blood pressure will be taken at least every four hours, as per protocol, either manually or with an automated device. Mean arterial pressure (MAP) will be calculated using a standard formula (MAP = diastolic blood pressure + 1/3 pulse pressure). Patients admitted to the ICU may have arterial lines placed for continuous blood pressure monitoring, if needed as part of their routine care. Routine blood chemistries, including serum creatinine and liver function tests will be drawn prior to administering drug or placebo.
At enrollment, the patient will be randomized to receive either valsartan or placebo. The first dose of study medication will not be administered until after the baseline MRI.
The patient will undergo an initial MRI that includes diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). The initial MRI is standard care for stroke patients. After the initial MRI, patients will be given a 160 mg dose of valsartan or placebo, in a double-blinded fashion. A sustained MAP reduction of 15-20% will be the goal. If the MAP remains within 15% of the initial value (prior to the first MRI scan) 24 hours after the first dose of valsartan (or placebo), the patients will be given a 320 mg dose of valsartan (or placebo) and will remain on valsartan 320 mg (or placebo) daily until day 7, or hospital discharge (whichever is sooner). If the MAP is falls by more than 20% after the 160 mg (or placebo) dose, the patient will be switched to 80 mg of valsartan (or placebo) until day 7, or hospital discharge (whichever is sooner). If the blood pressure is lowered by 15-20% (the goal), the patients will remain on valsartan 160 mg (or placebo) daily for the duration of the study.
A follow-up MRI with PWI and DWI will be obtained between 48-96 hours of the initial scan. Additional antihypertensive agents will not be administered until after the follow-up MRI scan unless deemed medically indicated by the attending physician. If additional agents are administered, any antihypertensive can be used except for an ACE inhibitor or ARB. Any additional agents needed for blood pressure control will be recorded.
The patient will continue taking valsartan vs. placebo throughout the duration of his/her hospitalization. At the time of discharge, an NIHSS and modified Rankin score will be recorded. On hospital day 7, or discharge (whichever is sooner), study medication will be discontinued and blood pressure medication will be at the discretion of the treating physician.
A 30-day follow-up will include assessment of a modified Rankin score and Glasgow Outcome Score. This 30 day follow-up will be conducted by telephone unless the patient is coming to the clinic for a routine hospital follow-up visit.
The patients will undergo two brain MRIs during the initial hospitalization, each requiring a scanning time of approximately 45 minutes. Standard sequences will be obtained, including DWI and PWI.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Condition ICMJE||Stroke, Acute|
|Intervention ICMJE||Drug: Valsartan
After the initial MRI, patients will be given a 160 mg dose of valsartan or placebo, in a double-blinded fashion. A sustained MAP reduction of 15-20% will be the goal. If the MAP remains within 15% of the initial value (prior to the first MRI scan) 24 hours after the first dose of valsartan (or placebo), the patients will be given a 320 mg dose of valsartan (or placebo) and will remain on valsartan 320 mg (or placebo) daily until day 7, or hospital discharge (whichever is sooner). If the MAP is falls by more than 20% after the 160 mg (or placebo) dose, the patient will be switched to 80 mg of valsartan (or placebo) until day 7, or hospital discharge (whichever is sooner). If the blood pressure is lowered by 15-20% (the goal), the patients will remain on valsartan 160 mg (or placebo) daily for the duration of the study.
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Estimated Enrollment ICMJE||20|
|Estimated Completion Date||February 2008|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01400256|
|Other Study ID Numbers ICMJE||CVAL489A US71|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Neil Schwartz, Stanford University|
|Study Sponsor ICMJE||Stanford University|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Stanford University|
|Verification Date||July 2011|
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