NanO2 in Large VessEL Occlusion Stroke (NOVEL)

Phase 2Not Yet RecruitingNCT06821347

NHS Greater Glasgow and Clyde172 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

172

Conditions

Stroke Acute

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

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

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

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)

Time frame: 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)