NanO2 in Large VessEL Occlusion Stroke (NOVEL) (NOVEL)

NanO2 in Large VessEL Occlusion Stroke (NOVEL): a Multicentre Single-blind, Randomised, Placebo-controlled Blinded Biomarker End-point Clinical Trial of Perfluorocarbon in Acute Ischaemic Stroke Due to Large Vessel Occlusion

This is a National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) clinical trial aiming to investigate a possible new treatment to limit damage to the brain caused by a stroke. Strokes that are caused by a clot blocking an artery in the brain ('ischaemic' strokes) starve brain tissue of oxygen and nutrients. Over a short period of time without oxygen, this tissue becomes permanently damaged. The trial aims to investigate the effects of a drug that carries extra oxygen, called NanO2, on the amount of brain tissue damage. By carrying extra oxygen to brain tissue NanO2 may allow the tissue to survive for longer. It might be especially useful to prevent further damage happening while treatments to try and open the blocked blood vessel are given. Treatments may include 'clot-busting' drugs, or procedures to physically open a blocked artery. These treatments are very effective, but take time to successfully open the blockage. The study will involve treating people as early as possible after the stroke, and comparing brain scans before and after treatment. Patients diagnosed with a stroke that has occurred within the past 9 hours will be eligible to participate. The study will involve 8-15 hospitals across the UK. Participation in the study will last approximately 90 days. The majority of the study assessments will be during the first 5 days during inpatient hospital stay. There will be a telephone follow-up at 30 days and 90 days post-discharge.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke Acute
• Intervention / Treatment: Drug: NanO2TM; Other: Sodium Chloride 0.9% Intravenous

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Keith Muir; Phone Number: +44 141 451 5892; Email: Keith.Muir@glasgow.ac.uk

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • NHS Greater Glasgow and Clyde
    • Contact: Keith Muir; Phone Number: +44 141 451 5892; Email: Keith.Muir@glasgow.ac.uk
    • Contact: Keith Muir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or non-pregnant female aged ≥ 18 years
2. Acute ischemic stroke fulfilling perfusion imaging criteria (ischemic core volume < 70 mL, mismatch ratio > 1.8 and mismatch volume > 15 mL using RAPID or equivalent CE-marked software)
3. Eligible for thrombolysis or thrombectomy
4. Intracranial LVO on CTA (occlusion of the terminal ICA, MCA-M1, ≥1 proximal MCA-M2, or proximal posterior cerebral artery (PCA-P1))
5. ≤ 9 hours after last known well (if waking with symptoms, last known well time is calculated as the mid-point between going to sleep and waking)
6. Pre-stroke functional independence (estimated pre-stroke mRS ≤2)
7. NIHSS score ≥ 6 (or NIHSS ≥ 2 if PCA-P1 occlusion) at randomisation

Exclusion Criteria:

1. History of significantly impaired renal eGFR (<30ml/min) or hepatic function (transaminases >3 times upper limit of normal or history of cirrhosis), unstable angina or heart failure (NYHA 3 or 4).
2. Pre-existing lung disease requiring supplemental chronic or intermittent oxygen therapy (NB oxygen therapy given post-stroke is not an exclusion)
3. Previous hypersensitivity reaction to NanO2 excipients and/or compounds similar to NanO2

4. Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation) or breast feeding women.

   Women of child-bearing potential is defined as experienced menarche; AND not undergone successful surgical sterilisation (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy); AND not post-menopausal i.e. amenorrhea for ≥12 consecutive months (without another medical cause)

5. Participation in another CTIMP within preceding 90 days or 5 half-lives of the investigational product, whichever is longer, or previous participation in NOVEL.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Sodium Chloride 0.9% Intravenous; Placebo
Experimental: NanO2	Drug: NanO2TM; Intravenous NanO2 0.17ml/kg (three doses given over 4.5 hours)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Volume of penumbral tissue salvaged based on follow-up imaging (diffusion weighted MRI, or non-contrast CT if MRI cannot be obtained) compared with pre-treatment penumbral tissue volume from CT Perfusion.	Baseline to 24hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		Baseline to Day 90
Cumulative incidence of Serious Adverse Events at 24h, day 5 and day 90		Baseline to Day 90
National Institutes of Health Stroke Scale (NIHSS) change from baseline to day 5	The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination in stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. Ratings for each item are scored with 3-5 grades with 0 normal, and there is an allowance for untestable items.	Baseline to Day 5
NIHSS score change from baseline to 24h	The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination in stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. Ratings for each item are scored with 3-5 grades with 0 normal, and there is an allowance for untestable items.	Baseline to 24hrs
24 hour NIHSS score	The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination in stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. Ratings for each item are scored with 3-5 grades with 0 normal, and there is an allowance for untestable items.	Baseline to 24hrs
Proportion achieving substantial early neurological improvement (NIHSS score reduced by ≥8 points or a score equal to 0 or 1) at 24 hours	The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination in stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. Ratings for each item are scored with 3-5 grades with 0 normal, and there is an allowance for untestable items.	Baseline to 24hrs
Distribution of modified Rankin Scale (mRS) scores at 30 and 90 days	The mRS is a hierarchial ordinal scale used to assess disability in stroke trials, with seven discrete levels that range from No Symptoms (mRS=0) to Death (mRS=6)	Baseline to Day 30 and Day 90
Proportion achieving independence (mRS score ≤2) at 90 days	The mRS is a hierarchial ordinal scale used to assess disability in stroke trials, with seven discrete levels that range from No Symptoms (mRS=0) to Death (mRS=6)	Baseline to Day 90
Proportion achieving excellent neurological outcome (mRS score 0-1) at 90 days	The mRS is a hierarchial ordinal scale used to assess disability in stroke trials, with seven discrete levels that range from No Symptoms (mRS=0) to Death (mRS=6)	Baseline to Day 90
Health-related Quality of Life using the EQ-5D score at 90 days	EQ5D is a standardised instrument for use as a measure of health outcome. EQ5D is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can take one of three responses reflecting severity (no problems / some or moderate problems / extreme problems). Participants are asked to rate their health today using a scale of 0 (worst health imaginable) to 100 (best health imaginable).	Baseline to Day 90

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow; NuvOx LLC

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: thrombolysis; large vessel occlusion; acute ischaemic stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: GN21ST331; NIHR151755 (Other Grant/Funding Number: National Institute for Health Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing will be facilitated in line with co-sponsor policies. Consent to share non-identifiable data with other researchers will be sought from study participants prior to participation.

Drug and device information, study documents

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