Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure

• Sponsor: Assistance Publique - Hôpitaux de Paris (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05586282
• Collaborator: (none)
• Enrollment: 380
• Anticipated Duration (Months): 41

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cardiogenic Shock; Postresuscitation Disease; Septic Shock

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 Design

• Study Type: Observational
• Anticipated Enrollment: 380 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Role of Candidate Proteins in Capillary Leakage During Acute Circulatory Failure
• Anticipated Study Start Date: Nov 1, 2022
• Anticipated Primary Completion Date: Mar 1, 2026
• Anticipated Study Completion Date: Apr 1, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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,…)

2. 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

3. Serum albuminemia [Day 0, Day 1, Day 3, Day 7, Day 14]

   g/L

4. Serum lactatemia [Day 0, Day 1, Day 3, Day 7, Day 14]

   mmoles/L

5. Arterial PaO2 [Day 0, Day 1, Day 3, Day 7, Day 14]

   (mmHg)

6. Circulating cytokine inflammatory profile IL-33 [Day 0, Day 1, Day 3, Day 7, Day 14]

   (pg/ml)

7. Circulating cytokine inflammatory profile TNF-alpha [Day 0, Day 1, Day 3, Day 7, Day 14]

   (pg/ml)

8. Circulating cytokine inflammatory profile IL-6 [Day 0, Day 1, Day 3, Day 7, Day 14]

   (pg/ml)

9. Circulating cytokine inflammatory profile IL-1 [Day 0, Day 1, Day 3, Day 7, Day 14]

   (pg/ml)

10. 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

11. Catecholamine-free days [Day 0 to Day 7, Day 30]

    Number of days alive without receiving any catecholamine

12. Ventilatory-free days [Day 0 to Day 7, Day 30]

    Number of days alive without receiving any machenical ventilation, invasive or non-invasive

13. Renal replacement therapy-free [Day 0 to Day 7, Day 30]

    Number of days alive without receiving any renal replacement therapy

14. Mortality [Day 30]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Assistance Publique - Hôpitaux de Paris

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT05586282
• Other Study ID Numbers: APH211381
• First Posted: Oct 19, 2022
• Last Update Posted: Oct 19, 2022
• Last Verified: Sep 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Post-Cardiac Arrest Syndrome; Shock, Cardiogenic; Shock

Study Results

No Results Posted as of Oct 19, 2022