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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

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.

Coordinator

EBERHARD KARLS UNIVERSITAET TUEBINGEN

Address

Geschwister-Scholl-Platz
72074 Tuebingen

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 498 742,74

Participants (11)

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KATHOLIEKE UNIVERSITEIT LEUVEN

Belgium

EU Contribution

€ 321 625

FAKULTNI NEMOCNICE U SV. ANNY V BRNE

Czechia

EU Contribution

€ 118 650

HELSINGIN JA UUDENMAAN SAIRAANHOITOPIIRIN KUNTAYHTYMÄ

Finland

EU Contribution

€ 137 463

CENTRE HOSPITALIER SAINTE ANNE DE PARIS

France

EU Contribution

€ 246 814

FUNDACIO HOSPITAL UNIVERSITARI VALL D'HEBRON - INSTITUT DE RECERCA

Spain

EU Contribution

€ 679 923,50

VASTRA GOTALANDS LANS LANDSTING

Sweden

EU Contribution

€ 185 600

CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS

Switzerland

EPPDATA GMBH

Germany

EU Contribution

€ 737 875

STROKE ALLIANCE FOR EUROPE

Belgium

EU Contribution

€ 66 625

UNIVERSITATSKLINIKUM HEIDELBERG

Germany

EU Contribution

€ 1 350 776,25

ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK

France

EU Contribution

€ 434 733

Project information

Grant agreement ID: 733379

Status

Ongoing project

  • Start date

    1 January 2017

  • End date

    31 December 2021

Funded under:

H2020-EU.3.1.3.

  • Overall budget:

    € 5 997 347,49

  • EU contribution

    € 5 778 827,49

Coordinated by:

EBERHARD KARLS UNIVERSITAET TUEBINGEN

Germany