Penumbral Rescue by Normobaric O2 Administration in Patients With Ischemic Stroke and Target Mismatch ProFile
- Conditions
- Acute Ischemic Stroke
- Interventions
- Other: Standard of care
- Registration Number
- NCT03500939
- Lead Sponsor
- University Hospital Tuebingen
- Brief Summary
The main objective of the PROOF trial is to investigate efficacy and safety of normobaric hyperoxygenation (NBHO) as a neuroprotective treatment in patients with acute ischemic stroke due to large vessel occlusion likely to receive endovascular mechanical thrombectomy (TBY) in a randomized controlled clinical phase IIb trial.
- Detailed Description
http://www.proof-trial.eu/
European Union's Horizon 2020 research and innovation programme grant 733379 (2016): Euro 5.8 Mio
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 223
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normobaric hyperoxygenation + standard of care Medical oxygen Normobaric hyperoxygenation (NBHO), i.e. inhalation of 100% oxygen at high flow (≥ 40 L/min) via a sealed non-rebreather face-mask with reservoir, or in case of intubation/ventilation for (study-independent) TBY, ventilation with an inspiratory oxygen fraction (FiO2) of 1.0. NBHO is started within 3 hours of stroke symptom onset (witnessed or last seen well) and within 20 minutes after end of baseline brain imaging and applied until the end of TBY procedure (defined by removal of guide catheter from sheath) or, in case TBY is not attempted, 4 hours after start of study treatment. Normobaric hyperoxygenation + standard of care Standard of care Normobaric hyperoxygenation (NBHO), i.e. inhalation of 100% oxygen at high flow (≥ 40 L/min) via a sealed non-rebreather face-mask with reservoir, or in case of intubation/ventilation for (study-independent) TBY, ventilation with an inspiratory oxygen fraction (FiO2) of 1.0. NBHO is started within 3 hours of stroke symptom onset (witnessed or last seen well) and within 20 minutes after end of baseline brain imaging and applied until the end of TBY procedure (defined by removal of guide catheter from sheath) or, in case TBY is not attempted, 4 hours after start of study treatment. standard of care alone Standard of care standard of care alone; oxygen supplementation if SpO2 ≤ 94% at 2 to 4 L/min via nasal cannula according to guidelines of the European Stroke Organisation (ESO), or in case of TBY-related intubation/ventilation, ventilation with an initial FiO2 of 0.3 to be gradually increased if SpO2 ≤ 94%.
- Primary Outcome Measures
Name Time Method ischemic core growth from baseline to 24 hours from baseline to 24 (22 to 36) hours difference in ischemic core volume (in mL) from baseline to 24 hours; intention-to-treat (ITT) analysis
- Secondary Outcome Measures
Name Time Method all-cause death 5 ± 2 days, 90 ± 10 days after randomization clinical safety endpoint; to be assessed at visit 6 (V6, day 5), and V7 (day 90)
National Institutes of Health Stroke Scale score (NIHSS) 20 ± 10 minutes, 4 hours ± 15 minutes, 24 ± 6 hours, 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; NIHSS to be assessed at visit 2 (V2, 20 minutes), V4 (end of study treatment), V5 (24 hours), V6 (day 5), and V7 (day 90); the NIHSS is a stroke severity score composed of 11 items (range from 0 to 41, higher values indicate more severe deficits)
Montgomery-Åsberg Depression Rating Scale (MADRS) 90 ± 10 days after randomization secondary clinical efficacy endpoint; MADRS to be assessed at visit 7 (day 90); the MADRS is a 10-item depression rating test that uses a 0 to 6 severity scale (higher scores indicate increasing depressive symptoms)
penumbral salvage from baseline to 24 hours from baseline to 24 (22 to 36) hours secondary imaging efficacy endpoint
modified Rankin Scale score (mRS) 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; mRS to be assessed at visit 6 (V6, day 5), and V7 (day 90); the mRs is an ordinal disability score of 7 categories (0 = no symptoms to 5 = severe disability, and 6 = death)
symptomatic intracranial hemorrhage 5 ± 2 days after randomization or discharge clinical safety endpoint; per ECASS III definition and per Heidelberg bleeding classification
vital signs 90 ± 10 days after randomization clinical safety endpoint; systolic and diastolic blood pressure, heart and respiratory rate, peripheral capillary oxygen saturation (SpO2)
concomitant invasive procedures 90 ± 10 days after randomization clinical safety endpoint; e.g. intravenous/intra-arterial thrombolysis, thrombectomy, stenting, carotid surgery, decompressive hemicraniectomy, cardioversion, patent foramen ovale (PFO) closure
relative changes in ischemic core volume (in %) from baseline to 24 hours from baseline to 24 (22 to 36) hours secondary imaging efficacy endpoint
survival 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; survival to be assessed at visit 6 (V6, day 5), and V7 (day 90)
Montreal Cognitive Assessment (MoCA) 90 ± 10 days after randomization secondary clinical efficacy endpoint; MoCA to be assessed at visit 7 (day 90)
length of ICU stay 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; length of ICU stay to be assessed at visit 6 (V6, day 5), and V7 (day 90); ICU is defined as a ward with capacity for mechanical ventilation and/or continuous monitoring of vital parameters (including stroke units)
duration of ventilation 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; duration of ventilation to be assessed at visit 6 (V6, day 5), and V7 (day 90)
change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 hours from baseline to 24 ± 6 hours key secondary endpoint; the NIHSS is a stroke severity score that is composed of 11 items; range from 0 to 41, higher values indicate more severe deficits
Barthel Index (BI) 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; BI to be assessed at visit 6 (V6, day 5), and V7 (day 90)
Stroke Impact Scale 16 (SIS-16) 90 ± 10 days after randomization secondary clinical efficacy endpoint; SIS-16 to be assessed at visit 7 (day 90); the SIS-16 is a 16-item physical dimension instrument for measuring the physical aspects of stroke recovery (items are rated on a 1 to 5 scale; 5 = not difficult at all, 1 = could not do at all)
EuroQoL Questionnaire (EQ-5D-5L) 90 ± 10 days after randomization secondary clinical efficacy endpoint; EQ-5D-5L to be assessed at visit 7 (day 90)
partial pressure of oxygen in the arterial blood (PaO2) 90 ± 30 minutes, 24 ± 6 hours after randomization secondary clinical efficacy endpoint; PaO2 to be assessed at visit 3 (90 minutes after start of study treatment), and V5 (24 hours)
length of hospital stay 5 ± 2 days, 90 ± 10 days after randomization secondary clinical efficacy endpoint; length of hospital stay to be assessed at visit 6 (V6, day 5), and V7 (day 90)
TICI (Thrombolysis in Cerebral Infarction perfusion scale grade) 4 hours ± 15 minutes secondary imaging efficacy endpoint; in patients who underwent mechanical thrombectomy (TBY)
new microbleeds on 24-hour follow-up MRI (vs. baseline T2*weighted MRI) 24 (22 to 36) hours imaging safety endpoints; only possible in patients who had MRI at baseline as well as at 24 hours
peri-interventional occurrence of vasospasms 4 hours ± 15 minutes imaging safety endpoints; in patients who underwent mechanical thrombectomy (TBY)
ischemic lesions in new territories on 24-hour follow-up imaging 24 (22 to 36) hours imaging safety endpoints
stroke related death 5 ± 2 days, 90 ± 10 days after randomization clinical safety endpoint; to be assessed at visit 6 (V6, day 5), and V7 (day 90)
12-lead electrocardiogram (ECG) 24 ± 6 hours after randomization clinical safety endpoint
safety laboratory 5 ± 2 days after randomization or discharge clinical safety endpoint; blood count, clinical chemistry, coagulation
absolute and relative ischemic core change from baseline to 24 hours using cerebral blood flow (CBF) < 30% for ischemic core estimation at baseline in all patients from baseline to 24 (22 to 36) hours secondary imaging efficacy endpoint; independent of imaging modality
revascularization on 24-hour follow-up imaging 24 (22 to 36) hours secondary imaging efficacy endpoint
any intracranial hemorrhage on 24-hour follow-up imaging 24 (22 to 36) hours imaging safety endpoints
Trial Locations
- Locations (22)
KU Leuven
🇧🇪Leuven, Belgium
UZ Gent
🇧🇪Gent, Belgium
CHU de Grenoble
🇫🇷Grendelbruch, France
CHU de Nice
🇫🇷Nice, France
Universitätsklinikum Gießen
🇩🇪Gießen, Germany
CHU de Liège
🇧🇪Liernu, Belgium
Helsinki University Hospital
🇫🇮Helsinki, Finland
CHU de Nancy
🇫🇷Nancy, France
Fondation Ophtalmologique Adolphe de Rothschild
🇫🇷Paris, France
Universitätsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Ludwig-Maximilians-Universität München
🇩🇪München, Germany
Centre Hospitalier Saint Anne de Paris
🇫🇷Paris, France
Universitätsklinikum Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
St. Lukas Klinik
🇩🇪Solingen, Germany
Fundacio Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
HCU Valladolid
🇪🇸Valladolid, Spain
AZ Groeninge Kortrijk
🇧🇪Kortrijk, Belgium
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
University Hospital Tuebingen
🇩🇪Tuebingen, Germany