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NCT Number: NCT06212492

Effects on Biotrauma of NMBAs and PP Association During ARDS

The improved survival of patients with acute respiratory distress syndrome (ARDS) over the last decades is related to the use of so-called "protective" mechanical ventilation. Two therapies have been shown to increase survival among the most hypoxemic patients (PaO2/FiO2 < 150 mmHg): a continuous use of neuromuscular blocking agents (NMBAs) for 48 hours in the acute phase of ARDS and prone positioning (PP). NMBAs and PP are part of the latest guidelines from French ICU Society. However, North American guidelines recommend PP for patients with severe ARDS only but not NMBAs, given the results of the ROSE study which did not confirm the benefit on mortality demonstrated in the ACURASYS study. However, in the ROSE study, ventilatory strategy, use of NMBAs and PP were different from the ACURASYS study.

Yet, NMBAs and PP are frequently associated in clinical practice, particularly with the COVID-19 pandemic, but also in randomized trials. In the PROSEVA study, almost all the patients (91%) received a continuous infusion of NMBAs during PP. Indeed, there is a common physiopathological rationale in both techniques: they favor the homogenization of transpulmonary pressures (TPP), reduce lung overdistension, Pendelluft effect and thus ventilator induced lung injury (VILI), in particular barotrauma and biotrauma. This reduction of biotrauma has been demonstrated for PP and NMBAs separately, but never by comparing the combined effect of the 2 techniques to each of them separately. This comparison requires reliable tools. In recent years, the "soluble form of the receptor for advanced glycation end products" (sRAGE), a new biomarker specific of pulmonary epithelial aggression and therefore of biotrauma, has been described and evaluated during ARDS and appears to be associated with the severity of pulmonary damage and prognosis.

Overall, despite an interesting physiopathological rationale and a clinically widespread practice, there is currently no study evaluating the synergistic effect of PP and NMBAs in the treatment of ARDS, in particular on the prevention of VILI, and more precisely of biotrauma. This question seems crucial to better specify the respective place of each of these treatments in the management strategy of ARDS patients whose prevalence and mortality remain high.

The objective of this study is therefore to evaluate, using a recent and reliable biomarker, the synergistic effect of a short-term NMBAs infusion using cisatracurium and PP on the reduction of biotrauma during moderate to severe ARDS. The investigators will compare this "synergistic" treatment to the use of PP alone. They will also evaluate, in secondary objectives, the effects of PP and NMBAs combination on clinical outcomes and on the patients' prognosis.

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Key information

Conditions

Moderate to Severe Acute Respiratory Distress Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service Médecine Intensive et Réanimation

Marseille, 13015, France

Location status: Recruiting

Location contact

Sami Hraiech, MD

CONTACT

[email protected]

0491964358 ext. +33

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age > 18 years
  • Written informed consent of proxy to the study participation
  • Invasive mechanical ventilation for ≤ 72 hours at inclusion
  • Criteria of moderate to severe ARDS according to the Berlin definition
  • Patients covered by or having the rights to social security

Exclusion criteria

  • Pregnant or breast-feeding women, patients deprived of freedom or under legal authority
  • Patients having undergone previous PP sessions during the same stay
  • Patients who had already been curarized prior to inclusion
  • Patient currently receiving ECMO or any technique of extracorporeal CO2 removal at the time of inclusion
  • Patient with a contraindication to PP
  • Previous hypersensitivity or anaphylactic reaction to any NMBA
  • Chronic respiratory insufficiency with oxygen or long-term ventilation
  • SAPS II score at the time of enrollment > 75
  • Patients who are moribund or for whom limitations of active therapies have been decided.

Treatment and study plan

NMBAs

Drug

Early and systematic use of NMBAs

Prone Positioning

Other

Early and systematic use of prone positioning

Primary outcomes

  1. Difference between the plasma sRAGE value at the end of the first PP session and the baseline value before PP (∆ sRAGE).

    Time frame: Day 1

    Our primary outcome will be the comparison of the differences in plasma sRAGE levels before and after the first PP session (∆ sRAGE), a kinetic being probably more relevant than a raw value, given the observed inter-individual variations of sRAGE at basal state.

Secondary outcomes

  1. Plasma determination of IL1 before the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  2. Plasma determination of IL1 1 hour after PP initiation at the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  3. Plasma determination of IL1 at the end of the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  4. Plasma determination of IL1 4 hours after return to supine after the first PP session

    Time frame: Day 2

    Inflammation, pulmonary epithelial and endothelial dysfunction

  5. Plasma determination of TNFα before the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  6. Plasma determination of TNFα 1 hour after PP initiation at the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  7. Plasma determination of TNFα at the end of the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  8. Plasma determination of TNFα 4 hours after return to supine after the first PP session

    Time frame: Day 2

    Inflammation, pulmonary epithelial and endothelial dysfunction

  9. Plasma determination of sRAGE before the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  10. Plasma determination of sRAGE 1 hour after PP initiation at the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  11. Plasma determination of sRAGE at the end of the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  12. Plasma determination of sRAGE 4 hours after return to supine after the first PP session

    Time frame: Day 2

    Inflammation, pulmonary epithelial and endothelial dysfunction

  13. Plasma determination of angiopoietin 2 before the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  14. Plasma determination of angiopoietin 2 1 hour after PP initiation at the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  15. Plasma determination of angiopoietin 2 at the end of the first PP session

    Time frame: Day 1

    Inflammation, pulmonary epithelial and endothelial dysfunction

  16. Plasma determination of angiopoietin 2 4 hours after return to supine after the first PP session

    Time frame: Day 2

    Inflammation, pulmonary epithelial and endothelial dysfunction

  17. PaO2/FiO2 before each PP session

    Time frame: Up to Day 28

    Hematosis

  18. PaO2/FiO2 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Hematosis

  19. PaO2/FiO2 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Hematosis

  20. PaO2/FiO2 at the end of each PP session

    Time frame: Up to Day 28

    Hematosis

  21. PaO2/FiO2 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Hematosis

  22. PaO2/FiO2 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Hematosis

  23. PaO2/FiO2 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Hematosis

  24. PaO2/FiO2 7 days after inclusion

    Time frame: 7 days after inclusion

    Hematosis

  25. pH before each PP session

    Time frame: Up to Day 28

    Hematosis

  26. pH 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Hematosis

  27. pH 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Hematosis

  28. pH at the end of each PP session

    Time frame: Up to Day 28

    Hematosis

  29. pH 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Hematosis

  30. pH 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Hematosis

  31. pH 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Hematosis

  32. pH 7 days after inclusion

    Time frame: 7 days after inclusion

    Hematosis

  33. PaCO2 before each PP session

    Time frame: Up to Day 28

    Hematosis

  34. PaCO2 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Hematosis

  35. PaCO2 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Hematosis

  36. PaCO2at the end of each PP session

    Time frame: Up to Day 28

    Hematosis

  37. PaCO2 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Hematosis

  38. PaCO2 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Hematosis

  39. PaCO2 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Hematosis

  40. PaCO2 7 days after inclusion

    Time frame: 7 days after inclusion

    Hematosis

  41. Plateau pressure (Pplat) before each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  42. Plateau pressure (Pplat) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  43. Plateau pressure (Pplat) 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  44. Plateau pressure (Pplat) at the end of each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  45. Plateau pressure (Pplat) 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  46. Plateau pressure (Pplat) 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Protective mechanical ventilation

  47. Plateau pressure (Pplat) 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Protective mechanical ventilation

  48. Plateau pressure (Pplat) 7 days after inclusion

    Time frame: 7 days after inclusion

    Protective mechanical ventilation

  49. Positive Expiratory Pressure (PEEP) before each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  50. Positive Expiratory Pressure (PEEP) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  51. Positive Expiratory Pressure (PEEP) 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  52. Positive Expiratory Pressure (PEEP) at the end of each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  53. Positive Expiratory Pressure (PEEP) 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  54. Positive Expiratory Pressure (PEEP) 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Protective mechanical ventilation

  55. Positive Expiratory Pressure (PEEP) 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Protective mechanical ventilation

  56. Positive Expiratory Pressure (PEEP) 7 days after inclusion

    Time frame: 7 days after inclusion

    Protective mechanical ventilation

  57. Driving Pressure (Δp) before each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  58. Driving Pressure (Δp) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28,

    Protective mechanical ventilation

  59. Driving Pressure (Δp) 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  60. Driving Pressure (Δp) at the end of each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  61. Driving Pressure (Δp) 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  62. Driving Pressure (Δp) 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Protective mechanical ventilation

  63. Driving Pressure (Δp) 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Protective mechanical ventilation

  64. Driving Pressure (Δp) 7 days after inclusion

    Time frame: 7 days after inclusion

    Protective mechanical ventilation

  65. Tidal Volume (Vt) before each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  66. Tidal Volume (Vt) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  67. Tidal Volume (Vt) 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  68. Tidal Volume (Vt) at the end of each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  69. Tidal Volume (Vt) 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  70. Tidal Volume (Vt) 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Protective mechanical ventilation

  71. Tidal Volume (Vt) 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Protective mechanical ventilation

  72. Tidal Volume (Vt) 7 days after inclusion

    Time frame: 7 days after inclusion

    Protective mechanical ventilation

  73. Respiratory Rate (Fr) before each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  74. Respiratory Rate (Fr) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  75. Respiratory Rate (Fr) 6 hours after PP initiation at each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  76. Respiratory Rate (Fr) at the end of each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  77. Respiratory Rate (Fr) 4 hours after return to supine after each PP session

    Time frame: Up to Day 28

    Protective mechanical ventilation

  78. Respiratory Rate (Fr) 48 hours after inclusion

    Time frame: 48 hours after inclusion

    Protective mechanical ventilation

  79. Respiratory Rate (Fr) 72 hours after inclusion

    Time frame: 72 hours after inclusion

    Protective mechanical ventilation

  80. Respiratory Rate (Fr) 7 days after inclusion

    Time frame: 7 days after inclusion

    Protective mechanical ventilation

  81. Esophageal pressure (for equipped sites) before each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  82. Esophageal pressure (for equipped sites) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  83. Esophageal pressure (for equipped sites) at the end of each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  84. Transpulmonary pressure (TPP) (for equipped sites) before each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  85. Transpulmonary pressure (TPP) (for equipped sites) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  86. Transpulmonary pressure (TPP) (for equipped sites) at the end of each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  87. Electrical Impedance Tomography data (for equipped sites) before each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  88. Electrical Impedance Tomography data (for equipped sites) 1 hour after PP initiation at each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  89. Electrical Impedance Tomography data (for equipped sites) at the end of each PP session

    Time frame: Up to Day 28

    Alveolar recruitment

  90. Pneumothorax

    Time frame: Within the first 7 days

    Barotrauma

  91. Pneumomediastinum

    Time frame: Within the first 7 days

    Barotrauma

  92. Sub cutaneous emphysema

    Time frame: Within the first 7 days

    Barotrauma

  93. Hospital mortality

    Time frame: At Day 28

  94. Hospital mortality

    Time frame: At Day 90

  95. Ventilator free days (VFD)

    Time frame: At Day 28

  96. Ventilator free days (VFD)

    Time frame: At Day 90

  97. Number of days alive without extra-respiratory organ failure

    Time frame: At Day 28

  98. Number of days alive without extra-respiratory organ failure

    Time frame: At Day 90

  99. Length of stay in intensive care unit

    Time frame: Maximum 3 months after inclusion (follow-up duration)

  100. Length of hospital stay

    Time frame: Maximum 3 months after inclusion (follow-up duration)

  101. Medical Research Council (MRC)

    Time frame: At day 28 or discharge

Study contacts

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

Sami Hraiech, MD

CONTACT

[email protected]

0491964358 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique Hopitaux De Marseille

Other

Registry information

Official study title

Effects on Biotrauma of Combining Routine CURArization With Prone Positioning During Adult Acute Respiratory Distress Syndrome

Acronym: CURA-PRONE

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jan 19, 2024
Registry last updated
Aug 20, 2024

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

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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.