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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.

Field of science

  • /medical and health sciences/basic medicine/neurology/stroke
  • /social sciences/economics and business/economics
  • /social sciences/economics and business
  • /social sciences/sociology/demography/mortality

Call for proposal

H2020-SC1-2016-RTD
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

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)

KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
EU contribution
€ 321 625
Address
Oude Markt 13
3000 Leuven
Activity type
Higher or Secondary Education Establishments
FAKULTNI NEMOCNICE U SV. ANNY V BRNE
Czechia
EU contribution
€ 118 650
Address
Pekarska 53
656 91 Brno
Activity type
Higher or Secondary Education Establishments
HELSINGIN JA UUDENMAAN SAIRAANHOITOPIIRIN KUNTAYHTYMÄ
Finland
EU contribution
€ 137 463
Address
Stenbackinkatu 9
00029 Helsinki
Activity type
Research Organisations
GROUPE HOSPITALIER UNIVERSITAIRE PARIS PSYCHIATRIE ET NEUROSCIENCES
France
EU contribution
€ 246 814
Address
Rue Cabanis 1
75014 Paris
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
FUNDACIO HOSPITAL UNIVERSITARI VALL D'HEBRON - INSTITUT DE RECERCA
Spain
EU contribution
€ 715 274,50
Address
Passeig Vall D Hebron 119-129 Edificio De Recerca
08035 Barcelona
Activity type
Research Organisations
VASTRA GOTALANDS LANS LANDSTING
Sweden
EU contribution
€ 185 600
Address
Regionens Hus
462 80 Vanersborg
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS
Switzerland
EU contribution
€ 26 225
Address
Rue Du Bugnon 21
1011 Lausanne
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
EPPDATA GMBH
Germany
EU contribution
€ 737 875
Address
Mehlbeerweg 10
22391 Hamburg
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
STROKE ALLIANCE FOR EUROPE
Belgium
EU contribution
€ 66 625
Address
Rue Washington 40
1050 Brussels
Activity type
Other
UNIVERSITATSKLINIKUM HEIDELBERG
Germany
EU contribution
€ 1 350 776,25
Address
Im Neuenheimer Feld 672
69120 Heidelberg
Activity type
Higher or Secondary Education Establishments
ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK
France
EU contribution
€ 373 157
Address
5 Rue Watt
75013 Paris
Activity type
Research Organisations