Copeptin Kinetics in Critically Ill Patients With Posterior Reversible Encephalopathy Syndrome

Posterior Reversible Encephalopathy Syndrome Clinical Trial

— XPRESSE  

Official title:

The Arginine Vasopressin aXis as a Potential Therapeutic Target for Posterior REverSible Encephalopathy SyndromE (XPRESSE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04950270
• Other study ID #: RIPH3-AOJCE20-BL-XPRESSE
• Status: Recruiting
• 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
• 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.

Related Conditions & MeSH terms

• Brain Diseases
• Posterior Reversible Encephalopathy Syndrome
• Syndrome

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