NanO2 in Large VessEL Occlusion Stroke (NOVEL)

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• 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 outcome measures (10)

• National Institutes of Health Stroke Scale (NIHSS) change from baseline to day 5 [Time frame: Baseline to Day 5]
• NIHSS score change from baseline to 24h [Time frame: Baseline to 24hrs]
• 24 hour NIHSS score [Time frame: 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 [Time frame: Baseline to 24hrs]
• Distribution of modified Rankin Scale (mRS) scores at 30 and 90 days [Time frame: Baseline to Day 30 and Day 90]
• Proportion achieving independence (mRS score ≤2) at 90 days [Time frame: Baseline to Day 90]
• Proportion achieving excellent neurological outcome (mRS score 0-1) at 90 days [Time frame: Baseline to Day 90]
• Health-related Quality of Life using the EQ-5D score at 90 days [Time frame: Baseline to Day 90]
• Mortality [Time frame: Baseline to Day 90]
• Cumulative incidence of Serious Adverse Events at 24h, day 5 and day 90 [Time frame: Baseline to Day 90]

Eligibility criteria

Inclusion criteria

• 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))
• ≤ 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)
• Pre-stroke functional independence (estimated pre-stroke mRS ≤2)
• NIHSS score ≥ 6 (or NIHSS ≥ 2 if PCA-P1 occlusion) at randomisation

Exclusion criteria

• 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.

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)

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• NHS Greater Glasgow and Clyde — Glasgow

Identifiers

NCT: NCT06821347 · GN21ST331 · NIHR151755

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗