Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study

Early Phase 1

• Conditions: Blood Pressure; Ischemic Stroke
• Interventions: Drug: Phenylephrine; Drug: Norepinephrine

• Registration Number: NCT04218773
• Lead Sponsor: Yale University

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.

Study Timeline

• Study First Submitted: 2019-12-20
• Study First Submitted QC: 2020-01-03
• Study First Posted: 2020-01-06
• Study Start: 2020-09-11
• Status Verified: 2024-09
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-03
• Primary Completion: 2025-06
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Induced hypertension	Norepinephrine	The scientists will investigate the potential consequences of increasing baseline systolic blood pressure with intravenous fluids and phenylephrine by 20% to at least 160 mmHg until blood vessel recanalization is achieved or the thrombectomy procedure is completed. The maximum allowed SBP is 220 mmHg or 180 mmHg, if intravenous TPA was administered.
Induced hypertension	Phenylephrine	The scientists will investigate the potential consequences of increasing baseline systolic blood pressure with intravenous fluids and phenylephrine by 20% to at least 160 mmHg until blood vessel recanalization is achieved or the thrombectomy procedure is completed. The maximum allowed SBP is 220 mmHg or 180 mmHg, if intravenous TPA was administered.

Primary Outcome Measures

Name	Time	Method
Primary Feasibility Outcome: Ability to achieve and maintain systolic blood pressure goals	Through completion of the thrombectomy procedure, an average of 2.5 hours	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.
Primary Safety Outcome: Number of patients with symptomatic intracranial hemorrhage	72 hours	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.

Secondary Outcome Measures

Name	Time	Method
Total number of serious adverse events	24 hours	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.

Trial Locations

Locations (1)

Yale-New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States