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Moderate to Severe Acute Respiratory Distress SyndromeCURA-PRONENCT06212492

Effects on Biotrauma of NMBAs and PP Association During ARDS

A study testing NMBAs and Prone positioning in people with Moderate to Severe Acute Respiratory Distress Syndrome, run by Assistance Publique Hopitaux De Marseille at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
NMBAs and Prone positioning
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteFrance
Study dates
8 Aug 2024to Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sami Hraiech, MD contact

0491964358 ext. +33

sami.hraiech@ap-hm.fr

France1 site, 1 recruiting

  • Service Médecine Intensive et Réanimation

    Marseille, 13015

    Sami Hraiech, MD, 0491964358 ext. +33, sami.hraiech@ap-hm.fr

    Recruiting

Other trials in France

About this study

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

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.

Read more

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.

Being tested
NMBAs, Prone positioning

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NMBAsDrug

    Early and systematic use of NMBAs

  • Prone positioningOther

    Early and systematic use of prone positioning

Study groups in NCT06212492
Study groupRoleWhat they receive
Prone Positioning and NMBAs (PP-NMBAs)ExperimentalEarly and systematic use of Prone positioning and NMBAs
Receives: Drug: NMBAs; Other: Prone positioning
Prone Positioning (PP)Active comparatorEarly and systematic use of prone positioning with NMBAs indicated ONLY as rescue
Receives: Other: Prone positioning

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: Day 1

Secondary outcomes (101)

  1. Plasma determination of IL1 before the first PP session

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 2

  5. Plasma determination of TNFα before the first PP session

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 2

  9. Plasma determination of sRAGE before the first PP session

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 2

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 1

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

    Inflammation, pulmonary epithelial and endothelial dysfunction

    Measured: Day 2

  17. PaO2/FiO2 before each PP session

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

  22. PaO2/FiO2 48 hours after inclusion

    Hematosis

    Measured: 48 hours after inclusion

  23. PaO2/FiO2 72 hours after inclusion

    Hematosis

    Measured: 72 hours after inclusion

  24. PaO2/FiO2 7 days after inclusion

    Hematosis

    Measured: 7 days after inclusion

  25. pH before each PP session

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

  28. pH at the end of each PP session

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

  30. pH 48 hours after inclusion

    Hematosis

    Measured: 48 hours after inclusion

  31. pH 72 hours after inclusion

    Hematosis

    Measured: 72 hours after inclusion

  32. pH 7 days after inclusion

    Hematosis

    Measured: 7 days after inclusion

  33. PaCO2 before each PP session

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

  36. PaCO2at the end of each PP session

    Hematosis

    Measured: Up to Day 28

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

    Hematosis

    Measured: Up to Day 28

  38. PaCO2 48 hours after inclusion

    Hematosis

    Measured: 48 hours after inclusion

  39. PaCO2 72 hours after inclusion

    Hematosis

    Measured: 72 hours after inclusion

  40. PaCO2 7 days after inclusion

    Hematosis

    Measured: 7 days after inclusion

  41. Plateau pressure (Pplat) before each PP session

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

  46. Plateau pressure (Pplat) 48 hours after inclusion

    Protective mechanical ventilation

    Measured: 48 hours after inclusion

  47. Plateau pressure (Pplat) 72 hours after inclusion

    Protective mechanical ventilation

    Measured: 72 hours after inclusion

  48. Plateau pressure (Pplat) 7 days after inclusion

    Protective mechanical ventilation

    Measured: 7 days after inclusion

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: 48 hours after inclusion

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

    Protective mechanical ventilation

    Measured: 72 hours after inclusion

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

    Protective mechanical ventilation

    Measured: 7 days after inclusion

  57. Driving Pressure (Δp) before each PP session

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28,

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

  62. Driving Pressure (Δp) 48 hours after inclusion

    Protective mechanical ventilation

    Measured: 48 hours after inclusion

  63. Driving Pressure (Δp) 72 hours after inclusion

    Protective mechanical ventilation

    Measured: 72 hours after inclusion

  64. Driving Pressure (Δp) 7 days after inclusion

    Protective mechanical ventilation

    Measured: 7 days after inclusion

  65. Tidal Volume (Vt) before each PP session

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

  70. Tidal Volume (Vt) 48 hours after inclusion

    Protective mechanical ventilation

    Measured: 48 hours after inclusion

  71. Tidal Volume (Vt) 72 hours after inclusion

    Protective mechanical ventilation

    Measured: 72 hours after inclusion

  72. Tidal Volume (Vt) 7 days after inclusion

    Protective mechanical ventilation

    Measured: 7 days after inclusion

  73. Respiratory Rate (Fr) before each PP session

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

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

    Protective mechanical ventilation

    Measured: Up to Day 28

  78. Respiratory Rate (Fr) 48 hours after inclusion

    Protective mechanical ventilation

    Measured: 48 hours after inclusion

  79. Respiratory Rate (Fr) 72 hours after inclusion

    Protective mechanical ventilation

    Measured: 72 hours after inclusion

  80. Respiratory Rate (Fr) 7 days after inclusion

    Protective mechanical ventilation

    Measured: 7 days after inclusion

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

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

    Alveolar recruitment

    Measured: Up to Day 28

  90. Pneumothorax

    Barotrauma

    Measured: Within the first 7 days

  91. Pneumomediastinum

    Barotrauma

    Measured: Within the first 7 days

  92. Sub cutaneous emphysema

    Barotrauma

    Measured: Within the first 7 days

  93. Hospital mortality

    Measured: At Day 28

  94. Hospital mortality

    Measured: At Day 90

  95. Ventilator free days (VFD)

    Measured: At Day 28

  96. Ventilator free days (VFD)

    Measured: At Day 90

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

    Measured: At Day 28

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

    Measured: At Day 90

  99. Length of stay in intensive care unit

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

  100. Length of hospital stay

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

  101. Medical Research Council (MRC)

    Measured: At day 28 or discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2024
  2. Study start8 Aug 2024
  3. Primary completionAug 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06212492
Sponsor's protocol ID
RCAPHM21_0414
Other IDs
ID-RCB
Acronym
CURA-PRONE
Status last verified
Dec 2023
First submitted
11 Dec 2023
Last updated
20 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Papazian L, Aubron C, Brochard L, Chiche JD, Combes A, Dreyfuss D, Forel JM, Guerin C, Jaber S, Mekontso-Dessap A, Mercat A, Richard JC, Roux D, Vieillard-Baron A, Faure H. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care. 2019 Jun 13;9(1):69. doi: 10.1186/s13613-019-0540-9.

    PubMed 31197492

  • National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19.

    PubMed 31112383

  • Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.

    PubMed 20843245

  • Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20.

    PubMed 23688302

  • Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.

    PubMed 26903337

Questions about this trial

What is this clinical trial studying?

A study testing NMBAs and Prone positioning in people with Moderate to Severe Acute Respiratory Distress Syndrome, run by Assistance Publique Hopitaux De Marseille at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sami Hraiech, MD (0491964358 ext. +33, sami.hraiech@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06212492, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.

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