Large vessel occlusion stroke Circulatory System
Conditions
Interventions
Participants will be randomised (1:1) to either NanO2 or placebo. A web-based system will be used to allocate treatment group. Participants randomised to the intervention arm will receive intravenous
Sponsors
University of Glasgow
NHS Greater Glasgow and Clyde
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 15/07/2026: 1. Male or non-pregnant female aged = 18 years 2. Intracranial LVO on CTA (occlusion of the terminal ICA, MCA-M1, =1 proximal MCA-M2, or proximal posterior cerebral artery (PCA-P1 or P2)) 3. = 24 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) 4. Pre-stroke functional independence (estimated pre-stroke mRS =2) 5. NIHSS score = 6 (or NIHSS = 2 if PCA occlusion) at randomisation 6. Imaging eligibility criteria: Meets acute ischemic stroke fulfilling perfusion imaging criteria using RAPID or equivalent CE-marked software: 6.1. Ischemic core volume 1.2 and 6.3. Mismatch volume >10 ml Previous inclusion criteria: 1. Male or non-pregnant female aged =18 years 2. Acute ischemic stroke fulfilling perfusion imaging criteria (ischemic core volume 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
Exclusion criteria: Current exclusion criteria as of 15/07/2026: 1. History of significantly impaired renal eGFR (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 childbearing potential, a negative pregnancy test will be required prior to randomisation) or breastfeeding women. Women of childbearing 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. Women of childbearing potential (WoCBP) or men with WoCBP partners who are unwilling to use adequate contraception measures for 6 months and 90 days, respectively, after dosing. Further information on contraception requirements is provided in Appendix 8 6. Participation in another CTIMP within the preceding 90 days or 5 half-lives of the investigational product, whichever is longer, or previous participation in NOVEL. Previous exclusion criteria: 1. History of significantly impaired renal eGFR (30 ml/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 childbearing potential, a negative pregnancy test will be required prior to randomisation) or breastfeeding women. Women of childbearing potential are 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
Design outcomes
Primary
| 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. Volume of penumbra – (24 h infarct volume – core volume). | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcomes as of 15/07/2026: Clinical: 1. National Institutes of Health Stroke Scale (NIHSS) change from baseline to day 5 2. NIHSS score change from baseline to 24 h 3. 24-hour NIHSS score 4. Proportion achieving substantial early neurological improvement (NIHSS score reduced by =8 points or a score equal to 0 or 1) at 24 hours 5. Distribution of modified Rankin Scale (mRS) scores at 30 and 90 days 6. Proportion achieving independence (mRS score =2) at 90 days 7. Proportion achieving excellent neurological outcome (mRS score 0-1) at 90 days 8. Health-related Quality of Life using the EQ-5D score at 90 days 9. Mortality 10. Cumulative incidence of serious adverse events at 24 h, day 7, and day 90 Mechanistic: 1. Volume of tissue infarction at 24-72h (volume of DWI lesion on MRI or hypoattenuated tissue on non-contrast CT if MRI cannot be obtained) 2. Volume of infarct growth (24-72h infarct volume minus core volume from CT perfusion) Previous secondary outcomes: Clinical: 1. National Institutes of Health Stroke Scale (NIHSS) change from baseline to day 5 2. NIHSS score change from baseline to 24 h 3. 24-hour NIHSS score 4. Proportion achieving substantial early neurological improvement (NIHSS score reduced by =8 points or a score equal to 0 or 1) at 24 hours 5. Distribution of modified Rankin Scale (mRS) scores at 30 and 90 days 6. Proportion achieving independence (mRS score =2) at 90 days 7. Proportion achieving excellent neurological outcome (mRS score 0-1) at 90 days 8. Health-related Quality of Life using the EQ-5D score at 90 days 9. Mortality 10. Cumulative incidence of serious adverse events at 24 h, day 7, and day 90 Mechanistic: 1. Volume of tissue infarction at 24h (volume of DWI lesion on MRI or hypoattenuated tissue on non-contrast CT if MRI cannot be obtained) | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactKeith Muir
Outcome results
None listed