Clinical trial NCT04218773: Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study
Official title: A Single Center, Pilot Study of Induced Hypertension for Minimizing Infarct Progression in Patients with Acute Large-vessel Occlusion Ischemic Stroke Undergoing Endovascular Therapy
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: EARLY_PHASE1
Conditions: Ischemic Stroke
Blood Pressure
Keywords: Induced hypertension
Blood pressure augmentation
Large-vessel occlusion
Thrombectomy
Endovascular therapy
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Feasibility Outcome: Ability to achieve and maintain systolic blood pressure goals
timeFrame: Through completion of the thrombectomy procedure, an average of 2.5 hours
measure: Primary Safety Outcome: Number of patients with symptomatic intracranial hemorrhage
timeFrame: 72 hours
Secondary outcomes:
measure: Total number of serious adverse events
timeFrame: 24 hours
Other outcomes:
measure: Recruitment feasibility: Rate of patient identification
timeFrame: Though study completion, an average of one year
measure: Recruitment feasibility: Rate of consent
timeFrame: Though study completion, an average of one year
measure: Recruitment feasibility: Enrollment rate
timeFrame: Though study completion, an average of one year
measure: Recruitment feasibility: Time to enrollment
timeFrame: Though study completion, an average of one year
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Nils H Petersen, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: