Penumbral Rescue by Normobaric O=O Administration in Patients With Ischemic Stroke and Target Mismatch ProFile: A Phase II Proof-of-Concept Trial
Overview
- Phase
- Phase 2
- Intervention
- Medical oxygen
- Conditions
- Acute Ischemic Stroke
- Sponsor
- University Hospital Tuebingen
- Enrollment
- 223
- Locations
- 22
- Primary Endpoint
- ischemic core growth from baseline to 24 hours
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Normobaric hyperoxygenation + 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.
Intervention: Medical oxygen
Normobaric hyperoxygenation + 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.
Intervention: Standard of care
standard of care alone
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%.
Intervention: Standard of care
Outcomes
Primary Outcomes
ischemic core growth from baseline to 24 hours
Time Frame: 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 Outcomes
- all-cause death(5 ± 2 days, 90 ± 10 days after randomization)
- 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)
- Montgomery-Åsberg Depression Rating Scale (MADRS)(90 ± 10 days after randomization)
- penumbral salvage from baseline to 24 hours(from baseline to 24 (22 to 36) hours)
- modified Rankin Scale score (mRS)(5 ± 2 days, 90 ± 10 days after randomization)
- symptomatic intracranial hemorrhage(5 ± 2 days after randomization or discharge)
- vital signs(90 ± 10 days after randomization)
- concomitant invasive procedures(90 ± 10 days after randomization)
- relative changes in ischemic core volume (in %) from baseline to 24 hours(from baseline to 24 (22 to 36) hours)
- survival(5 ± 2 days, 90 ± 10 days after randomization)
- Montreal Cognitive Assessment (MoCA)(90 ± 10 days after randomization)
- length of ICU stay(5 ± 2 days, 90 ± 10 days after randomization)
- duration of ventilation(5 ± 2 days, 90 ± 10 days after randomization)
- length of hospital stay(5 ± 2 days, 90 ± 10 days after randomization)
- TICI (Thrombolysis in Cerebral Infarction perfusion scale grade)(4 hours ± 15 minutes)
- new microbleeds on 24-hour follow-up MRI (vs. baseline T2*weighted MRI)(24 (22 to 36) hours)
- change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 hours(from baseline to 24 ± 6 hours)
- Barthel Index (BI)(5 ± 2 days, 90 ± 10 days after randomization)
- Stroke Impact Scale 16 (SIS-16)(90 ± 10 days after randomization)
- EuroQoL Questionnaire (EQ-5D-5L)(90 ± 10 days after randomization)
- partial pressure of oxygen in the arterial blood (PaO2)(90 ± 30 minutes, 24 ± 6 hours after randomization)
- peri-interventional occurrence of vasospasms(4 hours ± 15 minutes)
- ischemic lesions in new territories on 24-hour follow-up imaging(24 (22 to 36) hours)
- stroke related death(5 ± 2 days, 90 ± 10 days after randomization)
- 12-lead electrocardiogram (ECG)(24 ± 6 hours after randomization)
- safety laboratory(5 ± 2 days after randomization or discharge)
- 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)
- revascularization on 24-hour follow-up imaging(24 (22 to 36) hours)
- any intracranial hemorrhage on 24-hour follow-up imaging(24 (22 to 36) hours)