Blood PREssure Augmentation in Large-vessel Occlusion Stroke Study

Ischemic Stroke Clinical Trial

— 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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04218773
• Other study ID #: 2000022525
• Status: Enrolling by invitation
• Phase: Early Phase 1
• Start date: September 11, 2020
• Est. completion date: December 2024

Study information

• Verified date: June 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 40
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Blood Pressure
• Ischemic Stroke
• Stroke

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Yale-New Haven Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Recruitment feasibility: Enrollment rate	Patient enrollment rate will be calculated as enrolled patients per month.	Though study completion, an average of one year
Other	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
Primary	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	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	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