Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study (PRESS)

A Single Center, Pilot Study of Induced Hypertension for Minimizing Infarct Progression in Patients With Acute Large-vessel Occlusion Ischemic Stroke Undergoing Endovascular Therapy

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Ischemic Stroke; Blood Pressure
• Intervention / Treatment: Drug: Phenylephrine; Drug: Norepinephrine

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 Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Induced hypertension; 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.

Drug: Phenylephrine; 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.; Other Names: Neo-Synephrine; Drug: Norepinephrine; 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.; Other Names: Levophed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment feasibility: Rate of patient identification	Rate of patient identification will be calculated as the number of eligible patients who were identified and approached for consent by the study team divided by the number of eligible patients.	Though study completion, an average of one year
Recruitment feasibility: Rate of consent	Patient rate of consent will be calculated as the number of eligible patients who provided consent for participation divided by the total number of eligible patients.	Though study completion, an average of one year
Recruitment feasibility: Enrollment rate	Patient enrollment rate will be calculated as enrolled patients per month.	Though study completion, an average of one year
Recruitment feasibility: Time to enrollment	Time to enrollment will be assessed by calculating the time from ED presentation to enrollment in the study.	Though study completion, an average of one year

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Nils H Petersen, MD, MSc, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Thrombectomy; Endovascular therapy; Induced hypertension; Blood pressure augmentation; Large-vessel occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine; Oxymetazoline; Synephrine
• Other Study ID Numbers: 2000022525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No