Back to results

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

Primary Purpose

Ischemic Stroke, Blood Pressure

Status

Enrolling by invitation

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Phenylephrine

Norepinephrine

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Induced hypertension, Blood pressure augmentation, Large-vessel occlusion, Thrombectomy, Endovascular therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age is ≥18 years
Patients presenting with anterior circulation acute ischemic stroke
Enrollment within 24 hours of stroke onset
Treatment with endovascular thrombectomy
Arterial occlusion on CTA or MRA of the ICA, M1 or M2
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:

Baseline SBP>200 mm Hg
Intracranial hemorrhage (ICH) identified by CT or MRI
Inability to access the cerebral vasculature in the opinion of the neurointerventional team
Contraindication to imaging with MR
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
Acute myocardial infarction in the past 6 months
Signs or symptoms of acute myocardial infarction, including electrocardiogram find-ings, on admission
Elevated serum troponin concentration on admission (>0.1 μg/L)
Suspicion of aortic dissection on admission
Participation in any investigational study in the previous 30 days
Treatment with Monoamine oxidase inhibitors (MAO-I) within last 7 days

Sites / Locations

Yale-New Haven Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induced hypertension

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT04218773

First Posted

December 20, 2019

Last Updated

June 12, 2023

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT04218773

Brief Title

Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study

Acronym

PRESS

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

September 11, 2020 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Yale University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke, Blood Pressure

Keywords

Induced hypertension, Blood pressure augmentation, Large-vessel occlusion, Thrombectomy, Endovascular therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Induced hypertension

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Phenylephrine

Other Intervention Name(s)

Neo-Synephrine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Norepinephrine

Other Intervention Name(s)

Levophed

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

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

Title

Primary Safety Outcome: Number of patients with symptomatic intracranial hemorrhage

Description

Time Frame

72 hours

Secondary Outcome Measure Information:

Title

Total number of serious adverse events

Description

Time Frame

24 hours

Other Pre-specified Outcome Measures:

Title

Recruitment feasibility: Rate of patient identification

Description

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.

Time Frame

Though study completion, an average of one year

Title

Recruitment feasibility: Rate of consent

Description

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.

Time Frame

Though study completion, an average of one year

Title

Recruitment feasibility: Enrollment rate

Description

Patient enrollment rate will be calculated as enrolled patients per month.

Time Frame

Though study completion, an average of one year

Title

Recruitment feasibility: Time to enrollment

Description

Time to enrollment will be assessed by calculating the time from ED presentation to enrollment in the study.

Time Frame

Though study completion, an average of one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age is ≥18 years Patients presenting with anterior circulation acute ischemic stroke Enrollment within 24 hours of stroke onset Treatment with endovascular thrombectomy Arterial occlusion on CTA or MRA of the ICA, M1 or M2 Mismatch - Using CT or MRI with a Tmax >6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume. Mismatch ratio of greater than 1.8, and Absolute mismatch volume of greater than 15 ml, and Infarct core lesion volume of less than 70 mL Exclusion Criteria: Baseline SBP>200 mm Hg Intracranial hemorrhage (ICH) identified by CT or MRI Inability to access the cerebral vasculature in the opinion of the neurointerventional team Contraindication to imaging with MR 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 Acute myocardial infarction in the past 6 months Signs or symptoms of acute myocardial infarction, including electrocardiogram find-ings, on admission Elevated serum troponin concentration on admission (>0.1 μg/L) Suspicion of aortic dissection on admission Participation in any investigational study in the previous 30 days Treatment with Monoamine oxidase inhibitors (MAO-I) within last 7 days

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nils H Petersen, MD, MSc

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale-New Haven Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study

We'll reach out to this number within 24 hrs