Neutrophil elastase inhibition in acute lung injury: Results of the STRIVE study

Zeiher, Bernhardt; Artigas, Antonio; Vincent, Jean‐Louis; Dmitrienko, Alexei; Jackson, Kimberley; Thompson, B Taylor; Bernard, Gordon R.

doi:10.1097/01.ccm.0000133332.48386.85

Cited by 308 publications

(247 citation statements)

References 12 publications

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“…However, a subsequent multinational randomized double-blinded trial did not demonstrate the improvement in both short-term (28 days) and long-term (180 days) mortality (21). As a result, most countries have not approved sivelestat and it is not used for the treatment of ALI/ARDS.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) in the Treatment of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis

et al. 2010

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Introduction Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated. Methods We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model. Results 8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO2/FiO2 ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias. Conclusion Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.

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Section: Discussionmentioning

confidence: 99%

“…3). Predetermined sub-group analysis on studies conducted in Japan only, by excluding one study by Zeiher et al (21), again demonstrated no benefit of sivelestat on short term mortality (RR 0.59, CI 0.28-1.28) (Fig. 4).…”

Section: Mortalitymentioning

confidence: 92%

Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) in the Treatment of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis

et al. 2010

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“…For acute lung injuries in humans, the therapeutic dose of sivelestat is 0.2 mg/kg/h. In the STRIVE clinical study, however, sivelestat was not effective 10) . This finding was different from tests carried out in Japanese patients with less severe acute lung injury, where the treatment was effective 8) .…”

Section: Effects Of Pmx And/or Sivelestat On Lps-induced Increases Inmentioning

confidence: 90%

“…In Japan, sivelestat has been widely used in clinical practice since 2002. However, in the United States and Europe, the effectiveness of sivelestat was not observed in the multi-center, double-blind, placebo-controlled trial (STRIVE study) 10) .…”

Section: Introductionmentioning

confidence: 99%

Effects of simultaneous treatment with PMX-DHP and sivelestat on endotoxaemia in conscious guinea pigs

Ishinokami

Nemoto

Ninomiya

et al. 2012

Nihon Kyukyu Igakukai Zasshi

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Using an endotoxaemia model in conscious guinea pigs, we previously reported that polymyxin B immobilized fiber-direct hemoperfusion (PMX-DHP) or administration of sivelestat are effective treatments for sepsis. In the present study, we investigated whether simultaneous treatment with PMX-DHP and sivelestat sodium was more effective than either treatment alone for sepsis. Measurements examined included intestinal paralysis, blood pressure, serum HMGB1 level and survival rate. Colonic motion was monitored continuously by telemetry using a transducer attached to the taenia caecum, while blood pressure was monitored with a carotid artery catheter. The guinea pigs were divided into 4 groups and lipopolysaccharide (LPS) was administered to all animals. The control group received only LPS. The remaining three groups received PMX treatment for 2 hours, sivelestat sodium administration for 2 hours or simultaneous PMX and sivelestat treatment for 2 hours. In the control group, decreased colonic muscle tension and arterial pressure, and increased serum HMGB1 levels were observed and all animals died within 30 hours. In the PMX-DHP treated group, the decreases in colonic tension and arterial pressure were less severe than for the control group and the survival rate was higher than the control group, but serum HMGB1 levels were not significantly different. In the sivelestat group, decreases in colonic tension and arterial pressure were not significantly different with the control group, but serum HMGB1 levels were lower than in the control group. Simultaneous treatment with both PMX-DHP and sivelestat sodium did not exhibit synergistic effects for the treatment of LPS-induced endotoxaemia and mortality. PMX-DHP was effective at treating sepsis induced by administration of a high dose of LPS in guinea pigs, but simultaneous administration of sivelestat sodium did not augment the efficacy of PMX-DHP treatment. (JJAAM. 2012; 23: 12-20)

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“…However, it would give an unbalanced view if we did not mention that many well-performed studies have failed to show any survival benefit of disease modifying agents, such as surfactant therapy [21], activated protein C [22], inhaled nitric oxide [23] and, more recently, b-agonists [24] and neutrophil elastase inhibitors [25] amongst others in ongoing studies. Several ongoing trials are on the horizon [26].…”

mentioning

confidence: 99%

Topics in acute respiratory distress syndrome: the patient needs our tender loving and care

2014

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@ERSpublicationsThis editorial introduces a new series on acute respiratory distress syndrome summarising important clinical studies http://ow.ly/vDomD This editorial introduces a four-part series on acute respiratory distress syndrome (ARDS) that will cover a wide range of related topics in reviews written by internationally renowned experts. The first part of this series will be published in this issue of the European Respiratory Review by GUÉ RIN [1] on the role of prone positioning. This will be followed by articles on the topics of: 1) the role of imaging in the diagnosis and management of ARDS; 2) the novel ventilatory aspects involved in managing patients with ARDS; and 3) how to manage a patient failing conventional ventilation with extracorporeal support, in particular, extracorporeal membrane oxygenation (ECMO).It is nearly 50 years since the first report of ''acute respiratory distress in adults'' by ASHBAUGH et al. [2]. This later became known as ARDS and acute lung injury (ALI). This group of conditions was characterised by acute onset of hypoxaemia associated with the presence of bilateral infiltrates on chest radiography, poor lung compliance and the exclusion of cardiogenic pulmonary oedema [3]. ARDS may develop after a diverse spectrum of causes. These associated conditions may be categorised according to the nature of the insult with, for example, pulmonary sepsis causing a ''direct'' insult whilst pancreatitis and non-pulmonary sepsis cause an ''indirect'' insult resulting in ARDS often as part of multi-organ dysfunction syndrome. Despite some evidence of improvements in mortality in selected centres over recent decades, ARDS remains a major public health problem with a 28-day mortality in the region of 25-35%, and a corresponding large fiscal burden to national health services [4].In 1994, an American-European Consensus Conference (AECC) formalised the criteria for the diagnosis of ARDS and ALI. Thus, ARDS was defined by an arterial oxygen tension (PaO 2 )/inspiratory oxygen fraction (FIO 2 ) ratio of ,150 and ALI, at the milder end of the spectrum, as a PaO 2 /FIO 2 ratio of ,300 [5]. The definition of noncardiogenic pulmonary oedema was confirmed by a pulmonary artery wedge pressure of ,18 mmHg, necessitating the use of a Swan-Ganz catheter to make the formal definition. Although that definition is simple to apply in the clinical setting, it has been challenged over the years. For instance, it makes no sense that ALI could theoretically include all patients with a PaO 2 /FIO 2 ,300. It also makes no attempt to prognosticate in terms of severity of injury. Also, it does not take into account the effect of ventilatory support. In 2011, in an attempt to address these issues and others, experts from Europe and the

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Neutrophil elastase inhibition in acute lung injury: Results of the STRIVE study

Abstract: Intravenous sivelestat had no effect on 28-day all-cause mortality or ventilator-free days in a heterogeneous acute lung injury patient population managed with low tidal volume mechanical ventilation.

Cited by 308 publications

References 12 publications

Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) in the Treatment of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis

Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) in the Treatment of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis

Effects of simultaneous treatment with PMX-DHP and sivelestat on endotoxaemia in conscious guinea pigs

Topics in acute respiratory distress syndrome: the patient needs our tender loving and care

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