Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.
Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.
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常压O = O给药对缺血性卒中和靶点不匹配患者的半影拯救（PROOF）：IIb期试验的研究方案。
DOI：
10.1177/17474930231185275
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发表时间：
2024-01
影响因子：
6.7
通讯作者：
Tuennerhoff, Johannes
中科院分区：
文献类型：
--
作者：
Poli, Sven;Mbroh, Joshua;Baron, Jean-Claude;Singhal, Aneesh B.;Strbian, Daniel;Molina, Carlos;Lemmens, Robin;Turc, Guillaume;Mikulik, Robert;Michel, Patrik;Tatlisumak, Turgut;Audebert, Heinrich J.;Dichgans, Martin;Veltkamp, Roland;Huesing, Johannes;Graessner, Holm;Fiehler, Jens;Montaner, Joan;Adeyemi, Adedolapo Kamaldeen;Althaus, Katharina;Arenillas, Juan F.;Bender, Benjamin;Benedikt, Frank;Broocks, Gabriel;Burghaus, Ina;Cardona, Pere;Deb-Chatterji, Milani;Cvikova, Martina;Defreyne, Luc;De Herdt, Veerle;Detante, Olivier;Ernemann, Ulrike;Flottmann, Fabian;Guillamon, Lidia Garcia;Glauch, Monika;Gomez-Exposito, Alexandra;Gory, Benjamin;Grand, Sylvie Sylvie;Harsany, Michal;Hauser, Till Karsten;Heck, Olivier;Hemelsoet, Dimitri;Hennersdorf, Florian;Hoppe, Julia;Kalmbach, Pia;Kellert, Lars;Kohrmann, Martin;Kowarik, Markus;Lara-Rodriguez, Blanca;Legris, Loic;Lindig, Tobias;Luntz, Steffen;Lusk, Jay;Mac Grory, Brian;Manger, Andreas;Martinez-Majander, Nicolas;Mengel, Annerose;Meyne, Johannes;Muller, Susanne;Mundiyanapurath, Sibu;Naggara, Olivier;Nedeltchev, Krassen;Nguyen, Thanh N.;Nilsson, Maike A.;Obadia, Michael;Poli, Khouloud;Purrucker, Jan C.;Raty, Silja;Richard, Sebastien;Richter, Hardy;Schilte, Clotilde;Schlemm, Eckhard;Stohr, Linda;Stolte, Benjamin;Sykora, Marek;Thomalla, Goetz;Tomppo, Liisa;van Horn, Noel;Zeller, Julia;Ziemann, Ulf;Zuern, Christine S.;Hartig, Florian;Tuennerhoff, Johannes
氧气是细胞能量代谢所必需的。神经元特别容易受到缺氧的影响。在中风发作后立即增加氧气供应可以保护缺血半暗带直到血运重建发生。PROOF研究了在症状发作/注意到脑保护性桥接的6小时内使用常压氧（NBO）治疗，直至急性颅内前循环闭塞的血管内血运重建。随机化（1：1）、标准治疗对照、开放标签、设盲终点、多中心适应性IIb期试验。主要结局是从基线到24小时的缺血性核心生长（mL）（意向治疗分析）。次要疗效结局包括NIHSS从基线至24 h的变化、90天时的mRS、认知和情感功能以及生活质量。安全性结局包括死亡率、颅内出血和呼吸衰竭。将对影像学和血液生物标志物进行探索性分析。采用适应性设计，每组80例患者进行中期分析，假设标准差为21.4 mL，则需要多达456例受试者（每组228例）才能达到80%的把握度（单侧α 0.05），以检测缺血性核心生长平均减少6.68 mL。通过在早期时间窗内招募血管内血栓切除术候选者，该试验复制了临床前研究的见解，其中NBO显示出有益效果，即在短暂的暂时性缺血期间早期开始接近100%的吸入氧气。24小时随访成像的主要结局评估降低了因撤机和早期临床混杂因素（如延迟拔管和吸入性肺炎）引起的变异性。ClinicalTrials.gov：NCT 03500939; EudraCT：2017-001355-31。
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. 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. Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. 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. 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. 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. ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
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影响因子：
11.2
作者：
Flynn, EP;Auer, RN
通讯作者：
Auer, RN
影响因子：
9.9
作者：
Singhal, AB;Dijkhuizen, RM;Lo, EH
通讯作者：
Lo, EH
DOI：
10.1016/s0034-5687(01)00306-1
发表时间：
2001-11-15
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Erecinska, M;Silver, IA
通讯作者：
Silver, IA
影响因子：
168.9
作者：
Emberson, Jonathan;Lees, Kennedy R.;Lyden, Patrick;Blackwell, Lisa;Albers, Gregory;Bluhmki, Erich;Brott, Thomas;Cohen, Geoff;Davis, Stephen;Donnan, Geoffrey;Grotta, James;Howard, George;Kaste, Markku;Koga, Masatoshi;von Kummer, Ruediger;Lansberg, Maarten;Lindley, Richard I.;Murray, Gordon;Olivot, Jean Marc;Parsons, Mark;Tilley, Barbara;Toni, Danilo;Toyoda, Kazunori;Wahlgren, Nils;Wardlaw, Joanna;Whiteley, William;del Zoppo, Gregory J.;Baigent, Colin;Sandercock, Peter;Hacke, Werner
通讯作者：
Hacke, Werner
影响因子：
--
作者：
Beker MC;Caglayan AB;Kelestemur T;Caglayan B;Yalcin E;Yulug B;Kilic U;Hermann DM;Kilic E
通讯作者：
Kilic E