About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or non-pregnant female aged ≥ 18 years

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)

Eligible for thrombolysis or thrombectomy

Intracranial LVO on CTA (occlusion of the terminal ICA, MCA-M1, ≥1 proximal MCA-M2, or proximal posterior cerebral artery (PCA-P1))

Disqualifiers

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).

Pre-existing lung disease requiring supplemental chronic or intermittent oxygen therapy (NB oxygen therapy given post-stroke is not an exclusion)

Previous hypersensitivity reaction to NanO2 excipients and/or compounds similar to NanO2

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

Trial design

Design model

Parallel

Treatments tested in this trial

NanO2TM
Drug
Intravenous NanO2 0.17ml/kg (three doses given over 4.5 hours)
Sodium Chloride 0.9% Intravenous
Other intervention
Placebo

Treatment groups

172 Participants

are divided into 2 treatment groups

Group A: NanO2Experimental treatment 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame

Baseline to 24hrs

Secondary outcomes

1

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.

Time frame

Baseline to Day 5

2

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.

Time frame

Baseline to 24hrs

3

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.

Time frame

Baseline to 24hrs

4

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.

Time frame

Baseline to 24hrs

NanO2 in Large VessEL Occlusion Stroke (NOVEL)

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts