在 GAMES-RP 试验中，静脉注射格列吡嗪对已判决的水肿终点的影响。
Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial.
机构信息
From the Department of Neurology and Center for Genomic Medicine (W.T.K.), and Department of Radiology, Division of Neuroradiology (J.M.R.), Massachusetts General Hospital, Boston; Divisions of Stroke, Cerebrovascular and Critical Care Neurology (M.B.B.), Brigham & Women's Hospital, Boston, MA; Department of Neuroradiology (R.v.K.), Universitätsklinikum Carl Gustav Carus, Dresden, Germany; Calgary Stroke Program (A.M.D.), Department of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Canada; Department of Public Health Sciences (J.J.E.), Medical University of South Carolina, Charleston; Department of Neurology (H.E.H.), Oregon Health Sciences University, Portland; Department of Neurology (B.J.M.), University of Pittsburgh, PA; Department of Neurosurgery (J.M.S.), University of Maryland School of Medicine, Baltimore; and Division of Neurocritical Care and Emergency Neurology (K.N.S.), Yale New Haven Hospital, CT.
出版信息
Neurology. 2018 Dec 4;91(23):e2163-e2169. doi: 10.1212/WNL.0000000000006618. Epub 2018 Nov 16.
OBJECTIVE
In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints.
METHODS
Blinded adjudicators assigned designations for hemorrhagic transformation, neurologic deterioration, malignant edema, and edema-related death to patients from the GAMES-RP phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment on additional markers of edema and clinical deterioration were examined.
RESULTS
In the per-protocol sample, 41 patients received glyburide and 36 received placebo. There was no difference in the frequency of hemorrhagic transformation (n = 24 [58.5%] in IV glyburide vs n = 23 [63.9%] in placebo, = 0.91) or the incidence of malignant edema (n = 19 [46%] in IV glyburide vs n = 17 [47%] in placebo, = 0.94). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (n = 1 [2.4%] with IV glyburide vs n = 8 [22.2%] with placebo, = 0.01). In the subset of patients with malignant edema, those treated with IV glyburide had less midline shift ( < 0.01) and reduced MMP-9 (matrix metalloproteinase 9) levels ( < 0.01). The glyburide treatment group had lower rate of NIH Stroke Scale (NIHSS) increase of ≥4 during the infusion period (n = 7 [37%] in IV glyburide vs n = 12 [71%] in placebo, = 0.043), and of change in level of alertness (NIHSS subscore 1a; n = 11 [58%] vs n = 15 [94%], = 0.016).
CONCLUSION
IV glyburide was associated with improvements in midline shift, level of alertness, and NIHSS, and there were fewer deaths attributed to edema. Additional studies of IV glyburide in large hemispheric infarction are warranted to corroborate these findings.
CLINICALTRIALSGOV IDENTIFIER
NCT01794182.
LEVEL OF EVIDENCE
This study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.
目的
在 Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) 试验的二次分析中，我们报告了 IV 格列本脲对水肿相关终点的影响。
方法
盲法裁判将 II 期随机对照试验中与出血转化、神经功能恶化、恶性水肿和水肿相关死亡相关的设计名称分配给来自 GAMES-RP 阶段的 IV 格列本脲治疗大型大脑半球梗死的患者。在方案样本中比较了治疗组之间这些终点的发生率。在恶性水肿患者中，检查了治疗对其他水肿和临床恶化标志物的影响。
结果
在方案样本中，41 名患者接受了格列本脲治疗，36 名患者接受了安慰剂治疗。IV 格列本脲组（n = 24 [58.5%]）与安慰剂组（n = 23 [63.9%]）出血转化的频率无差异（ = 0.91），恶性水肿的发生率也无差异（n = 19 [46%]与 IV 格列本脲，n = 17 [47%]与安慰剂， = 0.94）。然而，IV 格列本脲治疗与脑水肿所致死亡率降低相关（n = 1 [2.4%]与 IV 格列本脲，n = 8 [22.2%]与安慰剂， = 0.01）。在恶性水肿患者亚组中，接受 IV 格列本脲治疗的患者中线移位减少（ < 0.01），基质金属蛋白酶 9（matrix metalloproteinase 9，MMP-9）水平降低（ < 0.01）。IV 格列本脲治疗组在输注期间 NIHSS 增加≥4 的发生率较低（n = 7 [37%]与 IV 格列本脲，n = 12 [71%]与安慰剂， = 0.043），警觉水平变化（NIHSS 亚评分 1a；n = 11 [58%]与 n = 15 [94%]， = 0.016）也较低。
结论
IV 格列本脲与改善中线移位、警觉水平和 NIHSS 有关，并且与水肿相关的死亡率降低。有必要进行更多的 IV 格列本脲治疗大型大脑半球梗死的研究，以证实这些发现。
临床试验注册标识符
NCT01794182。
证据水平
本研究提供了 II 级证据，表明对于大型大脑半球梗死患者，IV 格列本脲可改善一些与水肿相关的终点。
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