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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04950270
Other study ID # RIPH3-AOJCE20-BL-XPRESSE
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date June 18, 2022
Est. completion date June 2025

Study information

Verified date July 2023
Source University Hospital, Tours
Contact Charlotte SALMON GANDONNIERE, MD, PhD
Phone (+33)2 47 47 38 55
Email charlotte.salmon.gandonniere@gmail.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 24
Est. completion date June 2025
Est. primary completion date June 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Blood copeptin monitoring
Blood copeptin monitoring during the first 6 days of ICU stay with PRES
Other:
phone interview
Structured phone interview at 3 months to collect vital status and modified Rankin Scale score

Locations

Country Name City State
France University hospital Nantes
France Hospital Orléans
France University hospital Rennes
France University hospital Tours

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Estimation of time to maximum blood copeptin concentration (Tmax) Tmax will be estimated from copeptin kinetics: 6 samples at about 24 hours interval during the first 6 days of ICU stay with PRES Up to 120 hours post-baseline
Secondary Estimation of Tmax according to the etiology of PRES Up to 120 hours post-baseline
Secondary Estimation of Tmax according to the type of MRI-based brain edema at diagnosis Diffusion-weighted imaging (DWI) sequences and Apparent diffusion coefficient (ADC) maps will be used to discriminate a cytotoxic pattern of edema from a vasogenic edema Up to 120 hours post-baseline
Secondary Estimation of Area Under the Curve from D0 to D5 (AUC D0-D5) of blood copeptin according to the etiology of PRES AUC D0-D5 will be estimated from copeptin kinetics: 6 samples at about 24 hours interval during the first 6 days of ICU stay with PRES Up to 120 hours post-baseline
Secondary Estimation of AUC D0-D5 of blood copeptin according to the type of MRI-based brain edema at diagnosis DWI sequences and ADC maps will be used to discriminate a cytotoxic pattern of edema from a vasogenic edema Up to 120 hours post-baseline
Secondary Estimation of time to reach a copeptin concentration =50 pmol/L according to the etiology of PRES Up to 120 hours post-baseline
Secondary Estimation of time to reach a copeptin concentration =50 pmol/L according to the type of MRI-based brain edema at diagnosis DWI sequences and ADC maps will be used to discriminate a cytotoxic pattern of edema from a vasogenic edema Up to 120 hours post-baseline
Secondary Correlation analysis between AUC D0-D5 of blood copeptin and the extent of T2-FLAIR hyperintensities at diagnosis Up to 120 hours post-baseline
Secondary Correlation analysis between AUC D0-D5 of blood copeptin and ADC values at diagnosis Up to 120 hours post-baseline
Secondary Association analysis between AUC D0-D5 of blood copeptin and cerebral hemorrhagic lesions at diagnosis Up to 120 hours post-baseline
Secondary Association analysis between AUC D0-D5 of blood copeptin and contrast enhancement in the brain at diagnosis Up to 120 hours post-baseline
Secondary Correlation analysis between AUC D0-D5 of blood copeptin and AUC D0-D5 of mean arterial pressure Up to 120 hours post-baseline
Secondary Correlation analysis between AUC D0-D5 of blood copeptin and AUC D0-D5 of serum creatinine Up to 120 hours post-baseline
Secondary Association analysis between AUC D0-D5 of blood copeptin and Glasgow Outcome Scale score < 4 at ICU discharge Glasgow Outcome Scale score: [1: Death, 2: Persistent vegetative state, 3: Severe disability, 4: Moderate disability, 5: Low disability] 0, 24, 48, 72, 96, 120 hours post-baseline and ICU discharge
Secondary Association analysis between AUC D0-D5 of blood copeptin and modified Rankin Scale score = 4 at 3-month follow-up Day-90 modified Rankin scale will be determined during a structured phone interview.
Modified Rankin Scale score: [0: No symptoms at all, 1: No significant disability, 2: Slight disability, 3: Moderate disability, 4: Moderately severe disability, 5: Severe disability]
0, 24, 48, 72, 96, 120 hours post-baseline and 3 months
Secondary 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
See also
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