Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

Recruiting

• Conditions: Septic Shock; Postresuscitation Disease; Cardiogenic Shock

• Registration Number: NCT05586282
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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

Detailed 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.

Study Timeline

• Study First Submitted: 2022-10-11
• Study First Submitted QC: 2022-10-17
• Study First Posted: 2022-10-19
• Study Start: 2023-03-20
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-11
• Last Update Posted: 2024-10-15
• Primary Completion: 2026-03
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 380

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Fluid balance from Day 0 to day 3	Between Day 0 and 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,...)

Secondary Outcome Measures

Name	Time	Method
Fluid balance	Day 1, Day 3, Day 7, Day 14	(ml/kg of initial body weight). The fluid balance, routinely monitored in ICU, represents fluid intakes (perfusion, oral intakes,..) - fluid losses (diuresis, diarrhea,...)
Circulating cytokine inflammatory profile IL-33	Day 0, Day 1, Day 3, Day 7, Day 14	(pg/ml)
Circulating cytokine inflammatory profile TNF-alpha	Day 0, Day 1, Day 3, Day 7, Day 14	(pg/ml)
Ventilatory-free days	Day 0 to Day 7, Day 30	Number of days alive without receiving any machenical ventilation, invasive or non-invasive
Renal replacement therapy-free	Day 0 to Day 7, Day 30	Number of days alive without receiving any renal replacement therapy
Serum lactatemia	Day 0, Day 1, Day 3, Day 7, Day 14	mmoles/L
Circulating cytokine inflammatory profile IL-6	Day 0, Day 1, Day 3, Day 7, Day 14	(pg/ml)
Catecholamine-free days	Day 0 to Day 7, Day 30	Number of days alive without receiving any catecholamine
Mortality	Day 30
Extra-vascular lung water index	Day 0, Day 1, Day 3, Day 7, Day 14	Extra-vascular lung water index (EVLWi, ml/kg) and pulmonary vascular permeability index measured by transpulmonary thermodilution at corresponding time-points
Serum albuminemia	Day 0, Day 1, Day 3, Day 7, Day 14	g/L
SOFA score	Day 0, Day 1, Day 3, Day 7, Day 14	Association between circulating candidate proteins, the immune-inflammatory profile of the patients and SOFA score
Arterial PaO2	Day 0, Day 1, Day 3, Day 7, Day 14	(mmHg)
Circulating cytokine inflammatory profile IL-1	Day 0, Day 1, Day 3, Day 7, Day 14	(pg/ml)

Trial Locations

Locations (1)

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France