Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

• 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

Study Overview

• Status: Not yet recruiting
• Conditions: Septic Shock; Cardiogenic Shock; Postresuscitation Disease

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 Type: Observational
• Enrollment (Anticipated): 380

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients hospitalized in ICU with a circulatory failure due to septic shock, cardiogenic shock, or post-resuscitation syndrome.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with a circulatory failure; All patients hospitalized in ICU with a circulatory failure due to septic shock, cardiogenic shock, or post-resuscitation syndrome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		Day 30
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
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
Serum albuminemia	g/L	Day 0, Day 1, Day 3, Day 7, Day 14
Serum lactatemia	mmoles/L	Day 0, Day 1, Day 3, Day 7, Day 14
Arterial PaO2	(mmHg)	Day 0, Day 1, Day 3, Day 7, Day 14
Circulating cytokine inflammatory profile IL-33	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Circulating cytokine inflammatory profile TNF-alpha	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Circulating cytokine inflammatory profile IL-6	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
Circulating cytokine inflammatory profile IL-1	(pg/ml)	Day 0, Day 1, Day 3, Day 7, Day 14
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
Catecholamine-free days	Number of days alive without receiving any catecholamine	Day 0 to Day 7, Day 30
Ventilatory-free days	Number of days alive without receiving any machenical ventilation, invasive or non-invasive	Day 0 to Day 7, Day 30
Renal replacement therapy-free	Number of days alive without receiving any renal replacement therapy	Day 0 to Day 7, Day 30

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Postoperative Complications; Myocardial Infarction; Infarction; Brain Injuries; Reperfusion Injury; Shock; Shock, Cardiogenic; Post-Cardiac Arrest Syndrome
• Other Study ID Numbers: APH211381

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No