The Arginine Vasopressin aXis as a Potential Therapeutic Target for Posterior REverSible Encephalopathy SyndromE (XPRESSE)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Estimation of time to maximum blood copeptin concentration (Tmax)
研究概览
简要总结
XPRESSE is a multicenter observational prospective biomarker study in which critically ill patients with MRI-based PRES diagnosis will have copeptin kinetics from a daily blood sample for 6 days and a 3-month follow-up. This study aims to investigate the relationship between copeptin and PRES in order to establish the optimal therapeutic time window for vaptan treatment against PRES.
Data collection using an electronic case report form will include demographic data, medical history and data related to PRES: onset modalities and date of symptoms control, radiological features of PRES, biological investigations, results of etiological investigations and therapeutic management (e.g., anticonvulsants, antihypertensive drugs, supportive treatments). Outcomes will include modified Rankin scale score and Glasgow Outcome Scale score at ICU discharge, 3-month modified Rankin Scale score and 3-month mortality.
详细描述
Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity associating various neurological manifestations (e.g., encephalopathy, seizures) with a typical subcortical brain edema. While the pathophysiology of PRES remains elusive, the involvement of the arginine vasopressin (AVP) axis has recently been suggested by its stimulation in almost all etiologies of PRES as well as by its pathogenesis in the generation of brain edema that has been established in different preclinical models (e.g., traumatic brain injury, intracerebral hemorrhage) (Largeau et al., Mol Neurobiol 2019 - PMID: 30924075). Copeptin, a stable peptide derived from the same precursor as AVP and released in an equimolar ratio to AVP, is largely used in vivo to monitor AVP secretion. In a series of 225 critically ill patients free from PRES, median copeptin admission level was 50 pmol/L (Krychtiuk et al., PLOS ONE 2017- PMID: 28118414). By analogy to copeptin kinetics in patients with traumatic brain injury (Dong et al., J Trauma 2011 - PMID: 21502880), copeptin could attain peak level during the first week of PRES.
Blocking vasopressin receptors with vaptan appears to be a promising approach for PRES treatment. This study aims to investigate the relationship between copeptin and PRES in order to establish the optimal therapeutic time window for vaptan treatment against PRES.
XPRESSE is a multicenter observational prospective biomarker study in which critically ill patients in 4 French ICUs with MRI-based PRES diagnosis will have copeptin kinetics from a daily blood sample for 6 days and a 3-month follow-up.
Data collection using an eCRF will include demographic data, medical history and data related to PRES: onset modalities and date of symptoms control, radiological features of PRES, biological investigations, results of etiological investigations and therapeutic management (e.g., anticonvulsants, antihypertensive drugs, supportive treatments). Outcomes will include modified Rankin scale score and Glasgow Outcome Scale score at ICU discharge, 3-month modified Rankin Scale score and 3-month mortality.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years ;
- •Obtaining the non-opposition ;
- •Patient hospitalized in ICU;
- •PRES diagnosed within the last 48 hours (before admission or during ICU stay), based on the following clinico-radiological criteria :
- •Presentation with acute clinical symptoms ;
- •Presence of known risk factor for PRES;
- •Distributions of T2 weighted imaging (T2WI) or T2-fluid attenuated inversion recovery (T2-FLAIR) hyperintensities compatible with PRES imaging patterns ;
- •No other possible causes of these neuroimaging abnormalities found.
排除标准
- •Patient under legal protection ;
- •Patient under guardianship or curatorship
- •Pregnant women.
结局指标
主要结局
Estimation of time to maximum blood copeptin concentration (Tmax)
时间窗: Up to 120 hours post-baseline
Tmax will be estimated from copeptin kinetics: 6 samples at about 24 hours interval during the first 6 days of ICU stay with PRES
次要结局
- Estimation of time to reach a copeptin concentration ≤50 pmol/L according to the type of MRI-based brain edema at diagnosis(Up to 120 hours post-baseline)
- Correlation analysis between AUC D0-D5 of blood copeptin and AUC D0-D5 of serum creatinine(Up to 120 hours post-baseline)
- Correlation analysis between AUC D0-D5 of blood copeptin and ADC values at diagnosis(Up to 120 hours post-baseline)
- Association analysis between AUC D0-D5 of blood copeptin and cerebral hemorrhagic lesions at diagnosis(Up to 120 hours post-baseline)
- Association analysis between AUC D0-D5 of blood copeptin and mortality at 3-month follow-up(0, 24, 48, 72, 96, 120 hours post-baseline and 3 months)
- Estimation of Tmax according to the etiology of PRES(Up to 120 hours post-baseline)
- Estimation of Area Under the Curve from D0 to D5 (AUC D0-D5) of blood copeptin according to the etiology of PRES(Up to 120 hours post-baseline)
- Estimation of time to reach a copeptin concentration ≤50 pmol/L according to the etiology of PRES(Up to 120 hours post-baseline)
- Association analysis between AUC D0-D5 of blood copeptin and contrast enhancement in the brain at diagnosis(Up to 120 hours post-baseline)
- Estimation of Tmax according to the type of MRI-based brain edema at diagnosis(Up to 120 hours post-baseline)
- Estimation of AUC D0-D5 of blood copeptin according to the type of MRI-based brain edema at diagnosis(Up to 120 hours post-baseline)
- Correlation analysis between AUC D0-D5 of blood copeptin and the extent of T2-FLAIR hyperintensities at diagnosis(Up to 120 hours post-baseline)
- Correlation analysis between AUC D0-D5 of blood copeptin and AUC D0-D5 of mean arterial pressure(Up to 120 hours post-baseline)
- Association analysis between AUC D0-D5 of blood copeptin and Glasgow Outcome Scale score < 4 at ICU discharge(0, 24, 48, 72, 96, 120 hours post-baseline and ICU discharge)
- Association analysis between AUC D0-D5 of blood copeptin and modified Rankin Scale score ≥ 4 at 3-month follow-up(0, 24, 48, 72, 96, 120 hours post-baseline and 3 months)