Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial.
Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial.
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DOI：
10.1186/1745-6215-15-332
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发表时间：
2014-08-22
期刊：
影响因子：
2.5
通讯作者：
Thickett DR
中科院分区：
文献类型：
--
作者：
Greenwood H;Patel J;Mahida R;Wang Q;Parekh D;Dancer RC;Khiroya H;Sapey E;Thickett DR
在发达国家，社区获得性肺炎（CAP）被认为是传染病死亡的主要原因，而CAP的并发症——败血症是最常见和最具挑战性的——增加了死亡风险。在脓毒症的发展过程中，中性粒细胞“麻痹”状态的发展导致中性粒细胞抗微生物功能的损害，包括趋化性、活性氧的产生和中性粒细胞细胞外陷阱（NETs）的形成。中性粒细胞功能缺陷的机制仍然难以捉摸，尽管NET的形成与新生儿观察到的免疫抑制和脓毒症发生率增加有关。然而，越来越多的证据表明，他汀类药物能够调节败血症中中性粒细胞的功能，因为一些系统综述已经得出结论，他汀类药物在改善感染相关结果和死亡率方面发挥作用，同时，在体外，他汀类药物也被证明可以促进健康个体的NET形成。SNOOPI试验是一项4期随机安慰剂对照试验。本研究的目的是确定与安慰剂相比，口服辛伐他汀是否能优化老年脓毒性肺炎患者的中性粒细胞抗微生物功能，改善老年患者的预后。主要终点将是在接受辛伐他汀或安慰剂治疗的72至96小时内，测量对多种炎症介质（包括il - 8、f- met -亮氨酸和脂多糖）的反应。次要结局包括中性粒细胞迁移能力；活性氧产生；中性粒细胞吞噬能力；辛伐他汀在该患者组中的安全性和耐受性；中性粒细胞活化、炎症反应、肺泡上皮和内皮损伤的生物学标志物；系统内皮功能生物标志物和肺细胞外基质降解。本研究旨在招募60名患者入院伊丽莎白女王医院伯明翰nhs基金会信托。本研究将探讨体内辛伐他汀治疗在cap相关脓毒症中调节中性粒细胞抗微生物功能的能力。草案号：2012-003343-29（试验注册：2012年11月26日）。本文的在线版本（doi:10.1186/1745-6215-15-332）包含补充材料，可供授权用户使用。
Community-acquired pneumonia (CAP) is considered the leading cause of death from infectious disease in developed countries, while complications of CAP - sepsis being the most common and challenging - increase the risk of mortality. During the progression of sepsis, a state of neutrophil ‘paralysis’ develops resulting in the impairment of neutrophil anti-microbial functions including: chemotaxis, production of reactive oxygen species, and formation of neutrophil extracellular traps (NETs). Mechanisms underlying defective neutrophil function remain elusive although NET formation has been implicated in the immunosuppression and increased rates of sepsis observed in neonates. There is, however, increasing evidence that statins are able to modulate neutrophil function in sepsis as several systematic reviews have concluded that statins have a role in improving infection-related outcomes and mortality while, in vitro, statins have also been shown to boost NET formation in healthy individuals. The ‘SNOOPI’ trial is a phase 4, randomised placebo-controlled trial. The aim of this study is to determine whether oral treatment with simvastatin compared to placebo optimises neutrophil anti-microbial functions in elderly patients with septic pneumonia improving patient outcomes in the elderly. The primary outcome will be NET production within 72 to 96 hours of treatment with simvastatin or placebo measured in response to a number of inflammatory mediators, including IL8, f-Met-Leu-Phe and lipopolysaccharide. Secondary outcomes include neutrophil migratory capacity; reactive oxygen species production; neutrophil phagocytic capacity; safety and tolerability of simvastatin administration within this patient group; biological markers of neutrophil activation, the inflammatory response, alveolar epithelial and endothelial injury; systemic endothelial function biomarkers and pulmonary extracellular matrix degradation. This study aims to recruit 60 patients admitted into Queen Elizabeth Hospital Birmingham NHS-Foundation Trust. This study will investigate the ability of in vivo simvastatin therapy to modulate neutrophil anti-microbial functions in CAP-associated sepsis. EudraCT number: 2012-003343-29 (Trial Registered: 26 November 2012). The online version of this article (doi:10.1186/1745-6215-15-332) contains supplementary material, which is available to authorized users.
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影响因子：
20.3
作者：
Sapey, Elizabeth;Greenwood, Hannah;Lord, Janet M.
通讯作者：
Lord, Janet M.
影响因子：
9.8
作者：
Blackwell, TS;Christman, JW
通讯作者：
Christman, JW
影响因子：
3.7
作者：
Janda, Surinder;Young, Aaron;Swiston, John
通讯作者：
Swiston, John
DOI：
10.1136/bmj.c332
发表时间：
2010-03-23
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Schulz KF;Altman DG;Moher D;CONSORT Group
通讯作者：
CONSORT Group
DOI：
10.1186/cc11895
发表时间：
2012-12-11
期刊：
Critical care (London, England)
影响因子：
--
作者：
Patel JM;Snaith C;Thickett DR;Linhartova L;Melody T;Hawkey P;Barnett AH;Jones A;Hong T;Cooke MW;Perkins GD;Gao F
通讯作者：
Gao F