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Penumbral Rescue by Normobaric O=O Administration in Patients With Ischaemic Stroke and Target Mismatch ProFile: A Phase II Proof-of-Concept Trial

Objective

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 “bridging”, 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 ≤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.

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Programme(s)

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Topic(s)

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RIA - Research and Innovation action

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Call for proposal

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(opens in new window) H2020-SC1-2016-2017

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Coordinator

EBERHARD KARLS UNIVERSITAET TUEBINGEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 293 217,22
Address
GESCHWISTER-SCHOLL-PLATZ
72074 Tuebingen
Germany

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Region
Baden-Württemberg Tübingen Tübingen, Landkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 539 208,85

Participants (15)

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