Inhalation of oxygen at a normal pressure for penumbral rescue (rescue of not yet destroyed brain tissue) in patients with stroke due to a large vessel occlusion (ischemic stroke)
- Conditions
- Acute ischemic strokeMedDRA version: 21.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disordersMedDRA version: 21.1Level: LLTClassification code 10055221Term: Ischemic strokeSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2017-001355-31-ES
- Lead Sponsor
- Eberhard-Karls University Tübingen represented by University Hospital Tübingen and its Commercial Director
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 456
• Age: 18 to 80 years
• Clinical signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke
• LVO on CT angiography or MR angiography consistent with clinical signs and symptoms, i.e. either the terminal ICA with involvement of the M1-segment of the MCA/carotid-T, the proximal M1-segment, or the distal M1-segments (distal to perforating branches)
• Neither TBY nor IVT are a prerequisite for inclusion; patients not receiving TBY or IVT or both can be enrolled. Clinical treatment decisions should not delay study enrollment.
• NIHSS score of = 6 at screening
• NIHSS item 1a (level of consciousness) of 0 or 1
• Alberta Stroke Program Early CT score (ASPECTS) of 7-10 on non-contrast CT or 6-10 on diffusion-weighted MRI (DWI-MRI)
• CT perfusion (preferably whole-brain, minimal coverage = 75 mm) or MR perfusion imaging performed prior to NBHO
• NBHO can be initiated within 3 hours of certain stroke symptom onset (witnessed or last seen well) and within 20 minutes after end of baseline brain imaging (i.e. within 20 minutes after last image)
• Pre-stroke mRS of 0 or 1
• Breastfeeding women can participate, but must be instructed to stop breastfeeding after randomization
• Due to the emergency situation in which patients are enrolled and the presumed safety of the IMP as applied in the PROOF trial, their own written informed consent is not obtained prior to study inclusion but has to be gained as soon as possible. Patients who are able to give consent will be informed about trial participation orally and may consent to or decline participation. Patients unable to give consent will be enrolled through a deferred consent procedure
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 228
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 228
Neurological:
• Rapid improvement in neurological status to an NIHSS < 6 or evidence of vessel recanalization prior to randomization
• Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment
• Acute neurological symptoms related to other pathology than ischemic stroke
• Evidence of intracranial hemorrhage (except of cerebral microbleeds), intracranial tumor (except small meningioma), and/or intracranial arteriovenous malformation as confirmed by baseline brain imaging
• Intracranial aneurysm or prior stent implantation in the vascular territory (upstream and downstream) affected by qualifying LVO
• TBY procedure initiated (groin puncture) prior to randomization
• Previously known or CT angiographic / MR angiographic visualization of ipsilateral high-grade stenosis, complete cervical carotid occlusion, or flow-limiting carotid dissection
• Suspected aortic dissection or cerebral vasculitis based on medical history or CT angiography / MR angiography
• Clinical or imaging evidence of acute bilateral stroke or stroke in other vascular territories than qualifying LVO (except of clinically silent micro-lesions on DWI-MRI in patients who received MR-based acute brain imaging)
• Significant mass effect with midline shift as confirmed by brain imaging
• Any co-existing neurological (especially neuromuscular) disorder
Respiratory:
• Known history of chronic pulmonary disease (e.g. COPD, pulmonary fibrosis, alveolitis or pneumonitis)
• Any condition leading to hypoxic respiratory drive (e.g. neuromuscular disease)
• Prior to enrolment, > 2 L/min oxygen required to maintain peripheral oxygen saturation = 95%
• Acute respiratory distress that may, in the clinical judgment of the investigator, interfere with the study intervention
• Acute pneumonia, alveolitis or pneumonitis of viral, bacterial, fungal or any other etiology.
• Endotracheal intubation at time of screening or anticipated intubation for other reasons than TBY procedure
Other:
• Clinical suspicion of acute myocardial infarction (e.g. pressure or tightness in the chest, pain in the chest, back, jaw, and other areas of the upper body that lasts more than a few minutes or that goes away and comes back, shortness of breath)
• Baseline blood glucose of < 50 mg/dL (2.78 mmol) or > 400 mg/dL (22.20 mmol)
• Body temperature = 38.0°C at screening
• Presumed septic embolus, or suspicion of bacterial endocarditis
• History of severe allergy (more than rash) to contrast medium
• Current treatment with nitrofurantoin or amiodaron, paraquat poisoning, or history of treatment with bleomycin
• Pregnancy at screening, to be excluded (ß-HCG in serum or urine) in all women = 55 years except if surgically sterile; in women >55 years pregnancy must be excluded only in case of increased probability e.g. due to in-vitro fertilization
• Any co-existing or terminal disease (except qualifying stroke) with anticipated life expectancy of less than 6 months
• Any pre-existing condition that may, in the clinical judgment of the investigator, not allow safe participation in the study (e.g. alcohol or substance abuse, co-existing disease) or would complicate assessment of outcomes (e.g. dementia, psychiatric disease) or would confound the neurological or functional evaluations (e.g. dementia)
• Participation in another interventional (drug or device) study within the last four weeks
• Prior participation in the PROOF trial (no subject
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method