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NCT Number: NCT05586282

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

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • Affiliation to social security (AME excluded)
  • 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

  • Onset of shock (catecholamine infusion) >12 hours prior to inclusion
  • Age <18 year old
  • Pregnancy

Treatment and study plan

Primary outcomes

  1. Fluid balance from Day 0 to day 3

    Time frame: 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 outcomes

  1. Fluid balance

    Time frame: 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

    Time frame: 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

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    g/L

  4. Serum lactatemia

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    mmoles/L

  5. Arterial PaO2

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    (mmHg)

  6. Circulating cytokine inflammatory profile IL-33

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    (pg/ml)

  7. Circulating cytokine inflammatory profile TNF-alpha

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    (pg/ml)

  8. Circulating cytokine inflammatory profile IL-6

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    (pg/ml)

  9. Circulating cytokine inflammatory profile IL-1

    Time frame: Day 0, Day 1, Day 3, Day 7, Day 14

    (pg/ml)

  10. SOFA score

    Time frame: 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

    Time frame: Day 0 to Day 7, Day 30

    Number of days alive without receiving any catecholamine

  12. Ventilatory-free days

    Time frame: 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

    Time frame: Day 0 to Day 7, Day 30

    Number of days alive without receiving any renal replacement therapy

  14. Mortality

    Time frame: Day 30

Study contacts

Contact information is provided by the study sponsor or research team.

Nicolas BRECHOT, MD, PhD

CONTACT

[email protected]

+331 56 09 23 42

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Oct 19, 2022
Registry last updated
Oct 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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