Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy (RESCUE)

RESCUE: A Randomized, Blinded, Placebo-controlled, Parallel Group Design to Determine the Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy

A Phase II, randomized, blinded, placebo-controlled, parallel group study with patients experiencing a large vessel occlusion acute ischemic stroke who are selected for endovascular revascularization. Participants will be given a 48 h infusion of either 0.5 mL/kg/h RNS60 (up to a maximum of 60 mL/h), 1 mL/kg/h RNS60 (up to a maximum of 120 mL/h), or 1 mL/kg/h (up to a maximum of 120 mL/h) placebo (normal saline) starting within 30 minutes of consent after confirmation of candidacy for endovascular thrombectomy.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic
• Intervention / Treatment: Drug: RNS60; Drug: Placebo

Detailed Description

This study is a Phase II, randomized, blinded, placebo-controlled, parallel group design. Participants experiencing a large vessel occlusion acute ischemic stroke who are selected for endovascular revascularization will be given a 48 h infusion of either 0.5 mL/kg/h RNS60 (up to a maximum of 60 mL/h), 1 mL/kg/h RNS60 (up to a maximum of 120 mL/h), or 1 mL/kg/h (up to a maximum of 120 mL/h) placebo (normal saline) starting within 30 minutes of consent after confirmation of candidacy for endovascular thrombectomy and prior to arterial closure. Outcomes of the main trial will be evaluated throughout a 90 day observation period.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • The Hospital of the University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Center for Neurologic Research
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Acute ischemic stroke (AIS) selected for emergency endovascular treatment.
2. Age 18 years or older.
3. Onset (last-known-well) time to randomization time within 24 hours.

4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS)

   1. NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA) occlusion or
   2. NIHSS > 10 for M2-MCA occlusion.
5. Confirmed symptomatic intracranial occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA. Tandem extracranial carotid and intracranial occlusions are permitted.
6. Pre-stroke (24 hours prior to stroke onset) historical modified Rankin Scale (mRS) ≤2. Patient must be living without requiring nursing care.
7. Qualifying imaging performed less than 2 hours prior to randomization.
8. Consent process completed as per applicable laws and regulation and the IRB requirements.

Exclusion Criteria:

1. Evidence of a large core of established infarction defined as ASPECTS 0-4.
2. Evidence of absence of collateral circulation on qualifying imaging (Collateral score of 0 or 1).
3. Any evidence of intracranial hemorrhage or mass lesion on the qualifying imaging.
4. Planned use of an endovascular device not having approval or clearance by the relevant regulatory authority.
5. Endovascular thrombectomy procedure is completed as defined by the presence of arterial access closure.
6. Clinical history, past imaging or clinical judgment suggesting that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
7. Estimated or known weight > 130 kg (287 lbs).
8. Known pregnant/lactating female.

9. Myocardial infarction within 6 months prior to Screening including non-Q wave MI; Diagnosis of CHF with either:

   1. current clinical signs and symptoms of ventricular dysfunction (e.g., edema, shortness of breath),
   2. CHF medication adjustment within the prior 30 days or
   3. ejection fraction (if report available) of 30% or less measured in the 6 months prior to Screening; as either medically documented or reported by patient or another person considered by the Investigator to be reasonably reliable.
10. Known renal impairment defined as requiring renal replacement therapy (hemo- or peritoneal dialysis).
11. Inability to have MRI imaging (Non- MR compatible implants or any other foreseeable reason, including claustrophobia)
12. Severe or fatal comorbid illness that will prevent improvement or follow up.
13. Inability to complete follow-up treatment to Day 90.
14. Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding trial inclusion and throughout the duration of the trial.
15. Reported known seizure at time of stroke onset.
16. Ischemic stroke within previous 30 days.
17. Patients in normal sinus rhythm with a known QTcF > 450 ms at Screening.
18. Any other symptom that in the investigator's opinion may complicate or preclude the subject from participating in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RNS60 0.5 mL/kg/h; RNS60 0.5 mL/kg/h infusion for 48h (up to a maximum of 60 mL/kg) starting within 30 min of randomization (but prior to arterial access closure)	Drug: RNS60; RNS60 injection solution
Experimental: RNS60 1 mL/kg/h; RNS60 1 mL/kg/h infusion for 48h (up to a maximum of 120 mL/kg) starting within 30 min of randomization (but prior to arterial access closure)	Drug: RNS60; RNS60 injection solution
Placebo Comparator: Placebo 1 mL/kg/h; Placebo (normal saline) 1 mL/kg/h infusion for 48h (up to a maximum of 120 mL/kg) starting within 30 min of randomization (but prior to arterial access closure)	Drug: Placebo; Placebo injection solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with serious adverse events	90 days
Mortality: proportion of participants alive	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean mRS score	mRS = Modified Rankin Scale	90 days
Reduction in mortality rate	Lower event rate on the Kaplan Meier survival curve	90 days
Mean NIHSS score	NIHSS = National Institutes of Health Stroke Scale	90 days
Proportion of participants with a worsening of stroke	Worsening of stroke defined as progression, or hemorrhagic transformation, of the index stroke as documented by medical imaging and that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥4 point increase from lowest NIHSS during hospitalization and/or (c) results in death	90 days
Mean BI	Mean Barthel Index (BI) at Day 90 relative to pre-stroke BI	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct progression/regression	Infarct size measured by MRI brain imaging	90 days
Quality of life score	Health-related quality of life as measured by the 5-level EuroQoL 5D index (EQ-5D-5L)	90 days

Collaborators and Investigators

• Sponsor: Revalesio Corporation

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): November 8, 2023
• Study Completion (Actual): November 8, 2023

Study Registration Dates

• First Submitted: December 31, 2020
• First Submitted That Met QC Criteria: December 31, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Endovascular Thrombectomy
• 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; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Pharmaceutical Solutions; RNS60
• Other Study ID Numbers: 06.5.1.H1

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