Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

Septic Shock Clinical Trial

Official title:

Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05586282
• Other study ID #: APH211381
• Status: Not yet recruiting
• Start date: November 2022
• Est. completion date: April 2026

Study information

• Verified date: September 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

• Testing the association between circulating candidate proteins and the level of vascular leakage for three distinct forms of circulatory failure: cardiogenic shock, septic shock, and post-resuscitation syndrome.

• Describing immuno-inflammatory profiles associated with massive vascular leakage during those three forms of circulatory failure in humans

Description:

Circulatory shocks are responsible for one third of intensive care unit (ICU) admissions (20,000 patients per year in France) and are associated with 40% mortality [1,2]. Vascular hyperpermeability (also called vascular leakage) is a major feature of circulatory failure. During systemic inflammatory response syndrome (SIRS), massive vascular leakage affects macro and micro-circulation, and participates in the development of multiple organ failure [1,3]. Accordingly, fluid balance (the difference between fluid input and output) correlates independently with mortality during both septic and cardiogenic shock [4-7] and controlling capillary leakage was highly beneficial in numerous animal models of circulatory failure [8-10]. However, the determinants of vascular leakage remain poorly understood in humans.

The purpose of this study is to evaluate the link between circulatory levels of several proteins and the level of vascular leakage, in three distinct types of circulatory shocks.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 380
• Est. completion date: April 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent from patient or a legal representative/family member/close relative. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.

2. Affiliation to social security (AME excluded)

3. Patient with one of the circulatory failures described below:

• septic shock

• cardiogenic shock

• post-resuscitation syndrome

• Cardiogenic shock:

• Need for a catecholamine support to maintain mean arterial pressure>65 mmHg, AND

• Cardiac index <2 L/min/m2 or left ventricular ejection fraction (LVEF)<35%, AND

• Lactate >2.0 mmol/l

• Post-resuscitation syndrome:

• Cardiac arrest (absence of spontaneous respiration, palpable heartbeat, and responsiveness to stimuli> 1 min) with a compatible electrocardiogram (asystole/pulseless electrical activity/ventricular tachycardia), AND

• Need for a catecholamine support to maintain mean arterial pressure>65 mmHg, AND

• Lactate >2.0 mmol/l

• Septic shock:

• Suspected or proven bacterial infection

• Need for a vasopressor support to maintain mean arterial pressure>65 mmHg

• Lactate >2.0 mmol/l

• Cardiac index>3L/min/m2 or LVEF>40%

Exclusion Criteria:

1. Onset of shock (catecholamine infusion) >12 hours prior to inclusion

2. Age <18 year old

3. Pregnancy

Related Conditions & MeSH terms

• Cardiogenic Shock
• Post-Cardiac Arrest Syndrome
• Septic Shock
• Shock
• Shock, Cardiogenic

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

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, Day 14
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, Day 14
Secondary	Serum albuminemia	g/L	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Serum lactatemia	mmoles/L	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Arterial PaO2	(mmHg)	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Circulating cytokine inflammatory profile IL-33	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Circulating cytokine inflammatory profile TNF-alpha	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Circulating cytokine inflammatory profile IL-6	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Circulating cytokine inflammatory profile IL-1	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	SOFA score	Association between circulating candidate proteins, the immune-inflammatory profile of the patients and SOFA score	Day 0, Day 1, Day 3, Day 7, Day 14
Secondary	Catecholamine-free days	Number of days alive without receiving any catecholamine	Day 0 to Day 7, Day 30
Secondary	Ventilatory-free days	Number of days alive without receiving any machenical ventilation, invasive or non-invasive	Day 0 to Day 7, Day 30
Secondary	Renal replacement therapy-free	Number of days alive without receiving any renal replacement therapy	Day 0 to Day 7, Day 30
Secondary	Mortality		Day 30