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 65 mL/h), 1.0 mL/kg/h RNS60 (up to a maximum of 130 mL/h), or 1.0 mL/kg/h (up to a maximum of 130 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 65 mL/h), 1.0 mL/kg/h RNS60 (up to a maximum of 130 mL/h), or 1.0 mL/kg/h (up to a maximum of 130 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): 83
• 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 independently 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 Alberta Stroke Program Early Computerized Tomography Score (ASPECTS) 0-4.
2. Evidence of absence of collateral circulation on qualifying imaging (collateral score of 0 or 1 if multiphase computed tomography angiography (mCTA) is used, or absence of adequate ischemic penumbra in the judgment of the Investigator if computed tomographic perfusion (CTP) is used).
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 (MI) within 6 months prior to Screening including non-Q wave MI; Diagnosis of congestive heart failure (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 magnetic resonance imaging (MRI) (Non-magnetic resonance [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 > 460 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 65 mL/h) starting within 30 min of randomization (but prior to arterial access closure)	Drug: RNS60; RNS60 injection solution
Experimental: RNS60 1.0 mL/kg/h; RNS60 1.0 mL/kg/h infusion for 48h (up to a maximum of 130 mL/h) starting within 30 min of randomization (but prior to arterial access closure)	Drug: RNS60; RNS60 injection solution
Placebo Comparator: Placebo 1.0 mL/kg/h; Placebo (normal saline) 1.0 mL/kg/h infusion for 48h (up to a maximum of 130 mL/h) 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	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs)	An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in a congenital anomaly/birth defect. An SAE could also be an important medical event that may not have resulted in death, was life-threatening, or required hospitalization, but jeopardized the participant and required medical or surgical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs that started after the start of study drug infusion and are reported here.	From start of study drug administration up to Day 90
Mortality: Proportion of Participants Alive at Day 90		Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-disability Based on Modified Rankin Scale (mRS ) Score at Day 90	The mRS is a clinician-reported outcome measure for participants who have suffered a stroke. It measures functional recovery as the degree of disability or dependence in daily activities in a 6-point disability scale with possible scores ranging from 0 to 5: 0-no symptoms at all; 1-no significant disability despite symptoms; able to carry out all usual duties and activities; 2-slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3-moderate disability: requiring some help, but able to walk without assistance; 4-moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs without assistance; 5-severe disability; bedridden, incontinent, requiring constant nursing care and attention. A score of 6 is used for participants who expire (death). Non-disability was defined as a score ranging from 0 to 2. Disability was defined as a score ranging from 3-6.	Day 90
Change From Baseline in Infarct Volume of Stroke at 48 Hours	Infarct progression/regression was measured by Magnetic Resonance Imaging (MRI) of the brain. The mean change from post-EVT baseline in the volume of injured tissue was calculated at 48 hours.	Baseline, 48 hours
National Institutes of Health Stroke Scale (NIHSS) at 24 Hours	The NIHSS is a standardized neurological examination scale that is a measure of disability and recovery after acute stroke. The NIHSS assessment is a standardized 15-item impairment scale intended to evaluate neurologic outcome and degrees of recovery for subjects with stroke. The scale assesses levels of consciousness, extraocular movements, visual fields, facial muscle function, extremity strength, sensory function, coordination (ataxia), language (aphasia), speech (dysarthria), and hemi-inattention (neglect). The NIHSS was scored by those trained in the use of this scale. Each item was scored in ranges 0-2, 0-3, or 0-4. A score of 0 indicates normal performance. Total scores on the NIHSS ranged from 0-42, with higher values reflecting increasing severity. Stroke severity was further stratified in the following way: > 25: Very severe; 15-24: Severe; 5-14: Mild to moderately severe; < 5: Mild.	24 hours
Proportion of Participants With Worsening of Stroke	Worsening of stroke was defined as progression, or hemorrhagic transformation of the index stroke, as documented by brain imaging, which is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥ 4-point increase from lowest NIHSS pre-decline and/or (c) results in death. Proportion of participants with worsening of stroke was calculated as number of participants with worsening of stroke divided by the total number of participants observed over the 90-day period in each arm.	Up to Day 90
Percentage of Participants With Barthel Index (BI) Score ≥95 at Day 90	The BI is an index of functional independence. Its values range from 0 to 100, with higher scores indicating greater independence. Score range in BI items: Feeding 0-10; Bathing 0-5; Grooming 0-5; Dressing 0-10; Bowels 0-10; Bladder 0-10; Toilet use 0-10; Transfers (bed to chair and back) 0-15; Mobility (on level surfaces) 0-15; Stairs 0-10. Item scores vary in increments of 5 points. Functional independence at Day 90 was evaluated. Participants having a score ≥95 on the BI Score were deemed to have achieved functional independence, whereas those scoring <95 at Day 90 were deemed to have failed to achieve functional independence.	Day 90
Health-related Quality of Life as Measured by 5-Level EuroQoL 5D Index (EQ-5D-5L) at Day 90	EQ-5D-5L is a generic instrument for measuring health-related quality of life. It consists of a 5-item questionnaire, which was interviewer administered by study staff. The 5-item questionnaire comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and each dimension has 5 response levels (1-no problems, 2-slight problems, 3-moderate problems, 4-severe problems, 5-unable to/extreme problems). The health state is then summarized to be a single number, EQ-5D-5L Index score, by applying a country-specific standard value set. EQ-5D-5L Index score for the United States ranges from -0.59 to 1, where 1 indicates a better health condition.	Day 90

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

Publications and helpful links

General Publications

• Ghosh S, Dubow JS, Sutherland J, Smith W, Chiu D, Clark WM, Favilla CG, Ansari SA, Kalmes A, Mock J, Cook DJ, Madsen TE, Jayaraman M, Moldovan K, Torabi R, Liebeskind DS, Fisher M, McTaggart RA. Randomized, Proof-of-Concept Trial (RESCUE) of RNS60 as an Adjunct Therapy in Acute Ischemic Stroke. Stroke. 2025 Sep;56(9):2386-2397. doi: 10.1161/STROKEAHA.125.051179. Epub 2025 Jul 17.

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 (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Endovascular Thrombectomy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular 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