PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
UNASSIGNED: 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.
UNASSIGNED: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
摘要：
■氧气对细胞能量代谢至关重要。神经元特别容易缺氧。中风发作后不久增加氧气供应可以保留缺血半暗带，直到发生血运重建。
■PROOF研究了在急性颅内前循环闭塞的血管内血管内血运重建之前，症状发作/通知后6小时内使用常压氧（NBO）治疗脑保护性桥接。
■随机化(1:1)，标准治疗控制，开放标签，盲点，多中心适应性IIb期试验。
■主要结果是从基线到24小时的缺血核心生长（mL）（意向治疗分析）。次要疗效结果包括NIHSS从基线到24小时的变化，90天的mRS，认知和情感功能，和生活质量。安全性结果包括死亡率，颅内出血,和呼吸衰竭。将进行成像和血液生物标志物的探索性分析。
■使用适应性设计和中期分析，每臂80名患者，多达456名参与者（每个手臂228名）需要80％的功率（单侧α0.05）来检测平均减少6.68mL的缺血性核心生长，假设标准偏差为21.4毫升。
■通过在早期时间窗内登记血管内血栓切除术候选者，该试验复制了NBO表现出有益效果的临床前研究的见解，即在短暂的暂时缺血期间早期开始近100%的吸入氧。24小时随访影像学的主要结果评估可减少因停药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：NCT03500939；EudraCT：2017-001355-31。
■PROOF研究了在急性颅内前循环闭塞的血管内血管内血运重建之前，症状发作/通知后6小时内使用常压氧（NBO）治疗脑保护性桥接。
■随机化(1:1)，标准治疗控制，开放标签，盲点，多中心适应性IIb期试验。
■主要结果是从基线到24小时的缺血核心生长（mL）（意向治疗分析）。次要疗效结果包括NIHSS从基线到24小时的变化，90天的mRS，认知和情感功能，和生活质量。安全性结果包括死亡率，颅内出血,和呼吸衰竭。将进行成像和血液生物标志物的探索性分析。
■使用适应性设计和中期分析，每臂80名患者，多达456名参与者（每个手臂228名）需要80％的功率（单侧α0.05）来检测平均减少6.68mL的缺血性核心生长，假设标准偏差为21.4毫升。
■通过在早期时间窗内登记血管内血栓切除术候选者，该试验复制了NBO表现出有益效果的临床前研究的见解，即在短暂的暂时缺血期间早期开始近100%的吸入氧。24小时随访影像学的主要结果评估可减少因停药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：NCT03500939；EudraCT：2017-001355-31。
