PROOFProject ID: 733379
Penumbral Rescue by Normobaric O=O Administration in Patients With Ischaemic Stroke and Target Mismatch ProFile: A Phase II Proof-of-Concept Trial
Total cost:EUR 5 997 347,49
EU contribution:EUR 5 778 827,49
Call for proposal:H2020-SC1-2016-RTDSee other projects for this call
Funding scheme:RIA - Research and Innovation action
Ischemic stroke (IS), caused by occlusion of arteries that supply blood to the brain, remains a leading cause of mortality and morbidity in the world. Disruption of blood and oxygen supply to the brain leads to neuronal death in the ischemic core within minutes. The hypoperfused tissue surrounding the ischemic core, the penumbra, is at high risk for infarction over time but still salvageable. Neuroprotective â€œbridgingâ€, sustaining the penumbra until reperfusion, may widen the therapeutic window, make recanalization treatments accessible to more patients and improve overall IS outcomes.
As ischemic cell death is primarily mediated by hypoxia, increasing oxygen supply to the penumbra seems THE logical approach. In animal models of IS, normobaric hyperoxygenation (NBHO) significantly increased penumbral oxygen pressure and attenuated brain injury when initiated early after onset of ischaemia and vessel occlusion was transient (35 to 50% infarct volume reduction).
The PROOF project now seeks to demonstrate that NBHO (high-flow 100% oxygen at >45 L/min via a non-rebreather mask, or FiO2=1.0 for intubation/ventilation) reduces infarct growth from baseline to 24 hours compared to standard treatment if administered â‰¤3 hours after onset of anterior circulation IS, in patients with proximal vessel occlusion and salvageable tissue at risk. The study is multi-center, adaptive phase-IIb, randomized, open-label with blinded-endpoint (PROBE design).
The primary efficacy criterion will be infarct growth from baseline to 24 hours. Secondary endpoints will be NIHSS 24h, categorical shift in the pre-stroke modified Rankin Score, QoL and cognition at day 90.
Potential surrogate biomarkers, health economics and societal impacts will be assessed.
If NBHO proves its neuroprotective potential in this selected population, phase-III trials in all IS patients may be undertaken. Considering its low costs and ease of use, NBHO may impact stroke care worldwide.
EU contribution: EUR 1 498 742,74
EU contribution: EUR 321 625
Oude Markt 13
EU contribution: EUR 118 650
656 91 Brno
EU contribution: EUR 137 463
EU contribution: EUR 246 814
RUE CABANIS 1
75674 PARIS CEDEX 14
EU contribution: EUR 679 923,50
PASSEIG VALL D HEBRON 119-129 EDIFICIO DE RECERCA
EU contribution: EUR 185 600
462 80 VANERSBORG
EU contribution: EUR 0
RUE DU BUGNON 21
EU contribution: EUR 737 875
EU contribution: EUR 66 625
RUE WASHINGTON 40
EU contribution: EUR 1 350 776,25
IM NEUENHEIMER FELD 672
EU contribution: EUR 434 733
5 RUE WATT