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
Large vessel occlusion stroke
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 NanO2 0.17ml/kg (three doses over 4.5 hours. Participants randomised to the control arm will receive placebo (equal volumes of sodium chloride 0.9%). Trial assessments will take place at 24 hours and 5 days (or discharge date, if earlier) post randomisation. Follow-up assessments will take place remotely at Day 30 and Day 90.
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 <70 ml and 6.2. Mismatch ratio >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 <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
Current exclusion criteria as of 15/07/2026: 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 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