Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study

Early Phase 1SuspendedNCT04218773

Yale University40 enrolled

Overview

An open label, prospective, single center, pilot trial to assess feasibility and tolerability of short term blood pressure augmentation to minimize infarct progression in acute LVO stroke patients undergoing endovascular therapy.

The trial is planned to include 40 subjects with acute LVO stroke who meet the eligibility criteria. In stage 1 of the study, the investigators will monitor beat-to-beat blood pressure and other hemodynamic parameters in 20 patients receiving standard of care therapy. For the second stage, the investigators will enroll an additional 20 patients who will receive blood pressure augmentation therapy using intravenous fluids and phenylephrine or norepinephrine infusion. The investigators will increase baseline systolic blood pressure by 20% to at least 160 mmHg until blood vessel recanalization is achieved or the thrombectomy procedure is completed. The study will assess how quickly a target blood pressure can be reached in the acute stroke setting, and furthermore the ability to successfully maintain these blood pressure targets throughout the intervention and avoid hypotension during conscious sedation or general anesthesia. The primary research hypothesis of the trial is that treatment failure defined as an inability to achieve and maintain blood pressure targets despite the use of maximum tolerable doses of vasopressors (phenylephrine or norepinephrine) occurs in less than 20% of cases. In addition, the study will evaluate the recruitment feasibility and preliminary safety of blood pressure augmentation.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ischemic Stroke Blood Pressure

Interventions

PhenylephrineDRUG

Patients will receive intravenous phenylephrine at a rate of 60 µg/min. The infusion rate will be adjusted at 30 µg/min increments (maximum 180 µg/min) at 3-minute intervals to maintain an increase in SBP to the target SBP of 160 - 220 mmHg or a 20% increase above baseline SBP values.

NorepinephrineDRUG

As an alternative to intravenous phenylephrine, intravenous norepinephrine can be used with an initial infusion rate of 3 mcg/min. The initial infusion rate of norepinephrine will be adjusted at 1 mcg/min increments at 3-minute intervals to achieve and maintain the target blood pressure. Maximum dose is 25 mcg/min. Combination therapy with both agents (phenylephrine and norepinephrine) to achieve and maintain blood pressure targets is not permitted.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age is ≥18 years 2. Patients presenting with anterior circulation acute ischemic stroke 3. Enrollment within 24 hours of stroke onset 4. Treatment with endovascular thrombectomy 5. Arterial occlusion on CTA or MRA of the ICA, M1 or M2 6. Mismatch - Using CT or MRI with a Tmax \>6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume. 1. Mismatch ratio of greater than 1.8, and 2. Absolute mismatch volume of greater than 15 ml, and 3. Infarct core lesion volume of less than 70 mL Exclusion Criteria: 1. Baseline SBP\>200 mm Hg 2. Intracranial hemorrhage (ICH) identified by CT or MRI 3. Inability to access the cerebral vasculature in the opinion of the neurointerventional team 4. Contraindication to imaging with MR 5. A history of a left ventricular heart failure (NYHA Class ≥ III, or EF \< 50%) or angina (either unstable or CCS Grade II) involving symptoms at rest or with ordinary physical activity 6. Acute myocardial infarction in the past 6 months 7. Signs or symptoms of acute myocardial infarction, including electrocardiogram find-ings, on admission 8. Elevated serum troponin concentration on admission (\>0.1 μg/L) 9. Suspicion of aortic dissection on admission 10. Participation in any investigational study in the previous 30 days 11. Treatment with Monoamine oxidase inhibitors (MAO-I) within last 7 days

Locations (1)

Yale-New Haven Hospital

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Primary Feasibility Outcome: Ability to achieve and maintain systolic blood pressure goals

Percentage of treatment success is defined as the percentage of patients able to achieve target blood pressure within 60 minutes and maintain it throughout the procedure.

Time frame: Through completion of the thrombectomy procedure, an average of 2.5 hours

Primary Safety Outcome: Number of patients with symptomatic intracranial hemorrhage

Symptomatic intracerebral hemorrhage (sICH) is defined per SITS-MOST criteria as local or remote parenchymal hemorrhage type 2 on the post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h, or leading to death.

Time frame: 72 hours

Secondary Outcomes

Total number of serious adverse events

Number of treatment-related SAEs including but not limited to myocardial infarction, congestive heart failure and death during the first 24 hours from enrollment. Any SAE judged probably or definitely related to the study treatment is counted as a treatment-related SAE. The timeframe for SAE is based on the rapid onset and short half-life of phenylephrine and norepinephrine. Late SAEs are not expected to be related to treatment; however, these SAEs also are ascertained.

Time frame: 24 hours

Data from ClinicalTrials.gov

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