Determinants of Vascular Leakage During Systemic Inflammatory Response Syndrome

Systemic Inflammatory Response Syndrome Clinical Trial

— SIRS-PERM  

Official title:

Determinants of Vascular Leakage During Systemic Inflammatory Response Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05663216
• Other study ID #: APHP220418
• Status: Recruiting
• Start date: May 31, 2023
• Est. completion date: July 1, 2028

Study information

• Verified date: June 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Nicolas Brechot, MD,PhD
• Phone: 1-56-09-23-42
• Email: nicolas.brechot[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

BACKGROUND Controlling vascular leakage, which is independently associated with mortality during Sepsis and cardiogenic shock, may be a promising approach during systemic inflammatory response syndrome (SIRS). During a collaborative work between La Pitié-Salpêtrière intensive care unit (ICU) and the unit INSERM U1050 (National Institute oh Health and medical Research), we identified 38 genes associated with capillary leakage during systemic inflammation response syndrome (SIRS) in humans. The aim of this study is to evaluate their possible implication in vascular hyperpermeability associated with

METHODS SIRS-PERM is a prospective multicenter cohort study, testing the correlation between the plasma and broncho-alveolar levels of proteins isolated from our first screening, and the level of vascular leakage during SIRS. All patients admitted in the European Georges-Pompidou or La Pitié-Salpêtrière ICU and presenting a SIRS will be eligible for inclusion. Plasma samples will be collected at day 0, D1, D3 and D7, as well as broncho-alveolar lavage samples if clinically indicated. Concentration of each protein will be determined by ELISA in those samples. A statistical association will be then tested between each protein concentration and, for each time-point, the level of capillary leakage (daily weight and fluid balance, extra-vascular lung water index and pulmonary permeability index measured by transpulmonary thermodilution), and ARDS (acute respiratory distress syndrome) severity (PaO2/FiO2 ratio, Murray score and pulmonary compliance). Its link with hemodynamic status, the level of multiple organ failure, and vital status at day 30, will be also assessed. Basing the calculation of the sample size on the variations of VEGF (Vascular endothelial growth factor) expression in our first screening cohort, we calculated a sample size of 180 patients for this study, for a total duration of the study of 5 years.

IMPLICATIONS: SIRS-PERM will assess the determinants of capillary leakage during SIRS. It may thus provide a better understanding of the pathophysiology of this disease, with the goal to isolate new markers of severity, as well as new therapeutic targets to treat it. Modulating specifically capillary leakage is indeed a totally new approach during this pathology.

Description:

1. Intervention Six ml of blood will be sampled at Day 0 (beginning of the SIRS), D1, D3, D7. Concentrations of candidate proteins will be determined in the plasma by ELISA, and the link between each concentration and each outcome analyzed.

Additionally, broncho-alveolar lavage will be analyzed in the same way, if performed for the routine care of the patient.

2. Statistical analysis

The link between plasma and alveolar levels of each protein and each outcome will be evaluated, using Mann-Whitney U-test and one-way ANOVA for categorical variables (for example comparison of protein X plasma level between survivors or nonsurvivors at 30 days), and Pearson's correlation for continuous variables (for example link between protein X plasma level and daily fluid balance at each time point).

Sample size calculation. Plasma and pulmonary concentrations of each protein that we will study have never been described during SIRS. Based on our first screening cohort patients with severe capillary leakage had a difference in VEGF plasma concentration of 15.5 pg/ml, with a standard deviation of 32 pg/ml. Basing the calculation on this parameter, with an alpha risk of 5% and a power of 90%, a sample size of 180 patients would provide 90% chances to find a statistical link between one protein concentration and the outcomes of the patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: July 1, 2028
• Est. primary completion date: July 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients admitted in the European Georges Pompidou Hospital or La Pitié-Salpêtrière ICU, and exhibiting a systemic inflammatory response syndrome (SIRS), characterized by the following items:

• Temperature > 38°C ou <36°C

• Heart rate >90/min

• Respiratory rate >20/min or PaCO2<32mmHg

• White cell count > 12 000/mm3 ou < 4 000/mm3

Exclusion Criteria:

• Age <18 years

• Decline to participate

• Pregnancy

• Cirrhosis Child-Pugh > B

• Denutrition with BMI<15kg/m2

• Nephrotic syndrome

• Persons deprived of their liberty by a judicial or administrative decision (guardianship or tutelage measure)

Related Conditions & MeSH terms

• Syndrome
• Systemic Inflammatory Response Syndrome

Intervention

Other:
• Blood sampling
6 ml blood sampling at Day 0, 1, 3, 7. Broncho-alveolar sampling, if performed in routine care.

Locations

Country	Name	City	State
France	Medical Intensive Care Unit, Georges Pompidou European Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fluid balance from Day 0 to day 3 (ml/kg of initial body weight).	The fluid balance, routinely monitored in ICU, represents fluid intakes (perfusion, oral intakes,..) - fluid losses (diuresis, diarrhea,...)	Between Day 0 and Day 3
Secondary	Fluid balance (ml/kg of initial body weight).	The fluid balance, routinely monitored in ICU, represents fluid intakes (perfusion, oral intakes,..) - fluid losses (diuresis, diarrhea,...)	Day 1, Day 3, Day 7
Secondary	Extra-vascular lung water index	Extra-vascular lung water index (EVLWi, ml/kg) and pulmonary vascular permeability index measured by transpulmonary thermodilution at corresponding time-points	Day 0, Day 1, Day 3, Day 7
Secondary	SOFA score	Association between circulating candidate proteins, the immune-inflammatory profile of the patients and SOFA score (Sepsis-related Organ Failure Assessment), score values between 0-24, higher scores mean a worse outcome	Day 0, Day 1, Day 3, Day 7,
Secondary	Serum albuminemia	Serum albuminemia in g/L	Day 0, Day 1, Day 3, Day 7,
Secondary	Catecholamine-free days	Number of days alive without receiving any catecholamine	Day 0, Day 1, Day 3, Day 7, Day 30
Secondary	Ventilatory-free days	Number of days alive without receiving any mechanical ventilation, invasive or non-invasive	Day 0, Day 1, Day 3, Day 7, Day 30
Secondary	Renal replacement therapy-free Number of days alive without receiving any renal replacement therapy	Number of days alive without receiving any renal replacement therapy	Day 0, Day 1, Day 3, Day 7, Day 30
Secondary	Mortality		Day 30