Clinical trial NCT04950270: Copeptin Kinetics in Critically Ill Patients With Posterior Reversible Encephalopathy Syndrome
Official title: The Arginine Vasopressin aXis as a Potential Therapeutic Target for Posterior REverSible Encephalopathy SyndromE (XPRESSE)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Posterior Reversible Encephalopathy Syndrome
Keywords: Posterior Leukoencephalopathy Syndrome
Antidiuretic hormone
Intensive Care
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2021-07-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Critically ill adult patients in ICU with PRES

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Patient under legal protection ;
* Patient under guardianship or curatorship
* Pregnant women.

Primary outcomes:
measure: Estimation of time to maximum blood copeptin concentration (Tmax)
timeFrame: Up to 120 hours post-baseline
Secondary outcomes:
measure: Estimation of Tmax according to the etiology of PRES
timeFrame: Up to 120 hours post-baseline
measure: Estimation of Tmax according to the type of MRI-based brain edema at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Estimation of Area Under the Curve from D0 to D5 (AUC D0-D5) of blood copeptin according to the etiology of PRES
timeFrame: Up to 120 hours post-baseline
measure: Estimation of AUC D0-D5 of blood copeptin according to the type of MRI-based brain edema at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Estimation of time to reach a copeptin concentration ≤50 pmol/L according to the etiology of PRES
timeFrame: Up to 120 hours post-baseline
measure: Estimation of time to reach a copeptin concentration ≤50 pmol/L according to the type of MRI-based brain edema at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Correlation analysis between AUC D0-D5 of blood copeptin and the extent of T2-FLAIR hyperintensities at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Correlation analysis between AUC D0-D5 of blood copeptin and ADC values at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Association analysis between AUC D0-D5 of blood copeptin and cerebral hemorrhagic lesions at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Association analysis between AUC D0-D5 of blood copeptin and contrast enhancement in the brain at diagnosis
timeFrame: Up to 120 hours post-baseline
measure: Correlation analysis between AUC D0-D5 of blood copeptin and AUC D0-D5 of mean arterial pressure
timeFrame: Up to 120 hours post-baseline
measure: Correlation analysis between AUC D0-D5 of blood copeptin and AUC D0-D5 of serum creatinine
timeFrame: Up to 120 hours post-baseline
measure: Association analysis between AUC D0-D5 of blood copeptin and Glasgow Outcome Scale score < 4 at ICU discharge
timeFrame: 0, 24, 48, 72, 96, 120 hours post-baseline and ICU discharge
measure: Association analysis between AUC D0-D5 of blood copeptin and modified Rankin Scale score ≥ 4 at 3-month follow-up
timeFrame: 0, 24, 48, 72, 96, 120 hours post-baseline and 3 months
measure: Association analysis between AUC D0-D5 of blood copeptin and mortality at 3-month follow-up
timeFrame: 0, 24, 48, 72, 96, 120 hours post-baseline and 3 months
Other outcomes:
Locations:
city: Nantes
country: France
facility: University hospital
city: Orléans
country: France
facility: Hospital
city: Rennes
country: France
facility: University hospital
city: Tours
country: France
facility: University hospital
Study officials:
affiliation: University Hospital, Tours
name: Bérenger LARGEAU, PharmD
role: STUDY_CHAIR
affiliation: University Hospital, Tours
name: Charlotte SALMON GANDONNIERE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: