J 2024

Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial

POLI, Sven, Joshua MBROH, Jean-Claude BARON, Aneesh B SINGHAL, Daniel STRBIAN et. al.

Základní údaje

Originální název

Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial

Autoři

POLI, Sven, Joshua MBROH, Jean-Claude BARON, Aneesh B SINGHAL, Daniel STRBIAN, Carlos MOLINA, Robin LEMMENS, Guillaume TURC, Robert MIKULÍK (203 Česká republika, garant, domácí), Patrik MICHEL, Turgut TATLISUMAK, Heinrich J AUDEBERT, Martin DICHGANS, Roland VELTKAMP, Johannes HUESING, Holm GRAESSNER, Jens FIEHLER, Joan MONTANER, Adedolapo Kamaldeen ADEYEMI, Katharina ALTHAUS, Juan F ARENILLAS, Benjamin BENDER, Frank BENEDIKT, Gabriel BROOCKS, Ina BURGHAUS, Pere CARDONA, Milani DEB-CHATTERJI, Martina CVIKOVÁ (703 Slovensko, domácí), Luc DEFREYNE, De Herdt VEERLE, Olivier DETANTE, Ulrike ERNEMANN, Fabian FLOTTMANN, Lidia Garcia GUILLAMON, Monika GLAUCH, Alexandra GOMEZ-EXPOSITO, Benjamin GORY, Sylvie Sylvie GRAND, Michal HARŠÁNY (703 Slovensko, domácí), Till Karsten HAUSER, Olivier HECK, Dimitri HEMELSOET, Florian HENNERSDORF, Julia HOPPE, Pia KALMBACH, Lars KELLERT, Martin KOHRMANN, Markus KOWARIK, Blanca LARA-RODRIGUEZ, Loic LEGRIS, Tobias LINDIG, Steffen LUNTZ, Jay LUSK, Mac Grory BRIAN, Andreas MANGER, Nicolas MARTINEZ-MAJANDER, Annerose MENGEL, Johannes MEYNE, Susanne MULLER, Sibu MUNDIYANAPURATH, Olivier NAGGARA, Krassen NEDELTCHEV, Thanh N NGUYEN, Maike A NILSSON, Michael OBADIA, Khouloud POLI, Jan C PURRUCKER, Silja RATY, Sebastien RICHARD, Hardy RICHTER, Clotilde SCHILTE, Eckhard SCHLEMM, Linda STOHR, Benjamin STOLTE, Marek SYKORA, Goetz THOMALLA, Liisa TOMPPO, van Horn NOEL, Julia ZELLER, Ulf ZIEMANN, Christine S ZUERN, Florian HARTIG a Johannes TUENNERHOFF

Vydání

International Journal of Stroke, LONDON, SAGE PUBLICATIONS LTD, 2024, 1747-4930

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30210 Clinical neurology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 6.700 v roce 2022

Organizační jednotka

Lékařská fakulta

UT WoS

001063489000001

Klíčová slova česky

Normobaric oxygen therapy; NBO; hyperoxygenation; neuroprotection; penumbra; ischemic stroke; thrombectomy

Klíčová slova anglicky

Normobaric oxygen therapy; NBO; hyperoxygenation; neuroprotection; penumbra; ischemic stroke; thrombectomy

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 25. 1. 2024 12:06, Mgr. Tereza Miškechová

Anotace

V originále

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.Trial registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.

Návaznosti

90249, velká výzkumná infrastruktura
Název: CZECRIN IV