Hemodynamic Optimization of Cerebral Perfusion After Endovascular Therapy in Patients With Acute Ischemic Stroke (HOPE)

A Randomized Trial on Hemodynamic Optimization of Cerebral Perfusion After Endovascular Therapy in Patients With Acute Ischemic Stroke (HOPE Study)

Mechanical thrombectomy is a very effective treatment in patients who have suffered an acute ischemic stroke associated with intracranial large vessel occlusion. However, less than half of the patients achieve functional independence despite treatment. The optimization of blood pressure after mechanical thrombectomy based on the degree of recanalization achieved at the end of the procedure could improve the perfusion of the ischemic brain tissue thanks to the improvement of blood circulation provided by collateral circulation. For this, authorized hypotensive or hypertensive drugs will be used. Moreover, this individualized treatment would allow to decrease reperfusion injury and therefore decrease the risk of intracerebral bleeding complications and cerebral edema. Therefore, we designed a clinical trial in which the standard management of blood pressure after mechanical thrombectomy will be compared with a specific protocol in which blood pressure targets are applied according to the degree of recanalization obtained during the thrombectomy procedure. The beneficial effect and risk reduction of this treatment will translate into a better short and long-term outcome

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Other: Adjusted medication

• Study Type: Interventional
• Enrollment (Anticipated): 814
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joan Martí-Fàbregas, PhD, MD; Phone Number: 0034 93 5537636; Email: jmarti@santpau.cat
• Study Contact Backup: Name: Pol Camps-Renom, PhD, MD; Phone Number: 0034 935565986; Email: pcamps@santpau.cat

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital de La Santa Creu I Sant Pau
    • Contact: Joan Martí-Fàbregas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with acute ischemic stroke and large intracranial vessel occlusion within 24 hours after the onset of symptoms in whom mechanical thrombectomy has been performed.
• Successful recanalization, defined as a TICI score of 2b, 2c, or 3.
• Previous score on the modified Rankin scale (mRS) of 0, 1, or 2.
• The patient or her legal representative gives informed written or verbal consent

Exclusion Criteria:

• ASPECTS score <6
• Vertebral, basilar, A2, P2 and M3-4 occlusion
• History of intracerebral hemorrhage
• Pregnant or breastfeeding patient
• Patient with congestive heart failure or recent/unstable coronary artery disease (<3 months)
• Dissection of aorta, cervical or cerebral or unruptured aortic / cerebral aneurysm or known arteriovenous malformation
• Any bleeding visible on baseline CT
• History of ventricular arrhythmias
• Use of MAO inhibitors
• Inclusion in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment; Post-thrombectomy patients will have their blood pressure measured every hour for the first 24 hours after thrombectomy, and every 6 hours from 24 to 72 hours. The target blood pressure is not predefined by the study, but in patients who have received previous treatment with rt-PA, it is advisable to keep it below 180/110 mmHg. If the patient has not received rt-PA, there is no limitation, although the guidelines recommend keeping the pressure below 200/120 mmHg. The hypotensive or hypertensive treatments used will be noted.
Experimental: Optimized hemodynamic treatment; Post-thrombectomy patients will have their blood pressure measured every 30 minutes for the first 24 hours after thrombectomy, and every 1 hour from 24 to 72 hours. Blood pressure objectives will depend on the degree of recanalization achieved after thrombectomy (see intervention section). The hypotensive or hypertensive treatments used will be noted.	Other: Adjusted medication; In patients randomized to perfusion optimization, medication will be adjusted to maintain blood pressure according to the degree of recanalization: Patients with TICI 2b: systolic blood pressure 140-160 mmHg.; Patients with TICI 2c-3: systolic blood pressure <140 mmHg. Hypotensive drugs will be used when necessary. Intravenous labetalol is the treatment of choice, administered as a bolus or intravenous infusion. Alternative: urapidil (bolus or continuous infusion pump). If both drugs cannot be used or are insufficient, sodium nitroprusside can be used. Hypertensive drugs for TICI2b patients whose target pressure is 140-160mmHg and are below this range. Initially, a bolus of physiological saline or 100cc Plasmalyte® will be administered. If this treatment is not effective enough (blood pressure measurements persist <140 mmHg), intravenous phenylephrine will be administered.; Other Names: Phenylephrine; Urapidil; Labetalol; Sodium Nitroprusside; Physiological saline or Plasmalyte®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin scale value	State of functional independence, measured with the modified Rankin scale at 3 months (+/- 14 days).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIHSS score		24 hours
Mortality	Mortality from any cause at 3 months post-thrombectomy	3 months
Intracranial hemorrhagic complication	Rate of any intracranial hemorrhagic complication in the first 24 hours after the procedure.	24 hours
Intracranial hemorrhagic complication	Rate of any intracranial hemorrhagic complication in the first 72 hours after the procedure.	72 hours
Cerebral edema	Volume of cerebral edema at 24 hours in the post-thrombectomy CT scan.	24 hours
Cerebral edema	Volume of cerebral edema at 72 hours in the post-thrombectomy CT scan.	72 hours
Infarct size in the 24-hour post-thrombectomy CT.	Infarct size in the 24-hour post-thrombectomy CT.	24 hours
Infarct size in the 72-hour post-thrombectomy CT.	Infarct size in the 72-hour post-thrombectomy CT.	72 hours

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: May 14, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Serotonin Agents; Serotonin Receptor Agonists; Respiratory System Agents; Sympathomimetics; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Vasoconstrictor Agents; Mydriatics; Nitric Oxide Donors; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Labetalol; Phenylephrine; Urapidil; Nitroprusside
• Other Study ID Numbers: IIBSP-HOP-2021-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No