Effects on Biotrauma of NMBAs and PP Association During ARDS

NCT06212492 | Recruiting

• 2 other identifiers: RCAPHM21_0414ID-RCB
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Moderate to Severe Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (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.

  Day 1

Secondary Outcomes (101)

• Plasma determination of IL1 before the first PP session

  Day 1

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

  Day 1

• Plasma determination of IL1 at the end of the first PP session

  Day 1

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

  Day 2

• Plasma determination of TNFα before the first PP session

  Day 1

Study Arms (2)

Prone Positioning and NMBAs (PP-NMBAs)

EXPERIMENTAL

Early and systematic use of Prone positioning and NMBAs

Drug: NMBAs; Other: Prone positioning

Prone Positioning (PP)

ACTIVE COMPARATOR

Early and systematic use of prone positioning with NMBAs indicated ONLY as rescue

Other: Prone positioning

Interventions

NMBAs DRUG

Early and systematic use of NMBAs

Prone Positioning and NMBAs (PP-NMBAs)

Prone positioning OTHER

Early and systematic use of prone positioning

Prone Positioning (PP); Prone Positioning and NMBAs (PP-NMBAs)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Written informed consent of proxy to the study participation
• Criteria of moderate to severe ARDS according to the Berlin definition
• Patients covered by or having the rights to social security

You may not qualify if:

• Pregnant or breast-feeding women, patients deprived of freedom or under legal authority
• Patients having undergone previous PP sessions during the same stay
• 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.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Service Médecine Intensive et Réanimation

Marseille, 13015, France

RECRUITING

Related Publications (5)

• 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.

  PMID: 31197492 BACKGROUND

• 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.

  PMID: 31112383 BACKGROUND

• 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.

  PMID: 20843245 BACKGROUND

• 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.

  PMID: 23688302 BACKGROUND

• 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.

  PMID: 26903337 BACKGROUND

MeSH Terms

Interventions

Prone Position

Intervention Hierarchy (Ancestors)

Posture; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• François Cremieux

  AP-HM

  STUDY DIRECTOR

Central Study Contacts

Sami Hraiech, MD

CONTACT

0491964358; sami.hraiech@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: January 19, 2024
• Study Start: August 8, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 20, 2024

Record last verified: 2023-12

Locations

FR (1)