Effects on Biotrauma of NMBAs and PP Association During ARDS

NCT ID: NCT06212492

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-08
• Study Completion Date: 2026-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Prone Positioning and NMBAs (PP-NMBAs)

Early and systematic use of Prone positioning and NMBAs

Group Type: EXPERIMENTAL

NMBAs

Intervention Type: DRUG

Early and systematic use of NMBAs

Prone positioning

Intervention Type: OTHER

Early and systematic use of prone positioning

Prone Positioning (PP)

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

Group Type: ACTIVE_COMPARATOR

Prone positioning

Intervention Type: OTHER

Early and systematic use of prone positioning

Interventions

NMBAs

Early and systematic use of NMBAs

Intervention Type: DRUG

Prone positioning

Early and systematic use of prone positioning

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François Cremieux

Role: STUDY_DIRECTOR

AP-HM

Locations

Service Médecine Intensive et Réanimation

Marseille, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Sami Hraiech, MD

Role: CONTACT

sami.hraiech@ap-hm.fr

0491964358 ext. +33

Facility Contacts

Sami Hraiech, MD

Role: primary

sami.hraiech@ap-hm.fr

0491964358 ext. +33

References

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.

Reference Type: BACKGROUND

PMID: 31197492 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31112383 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20843245 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 23688302 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26903337 (View on PubMed)

Other Identifiers

ID-RCB

Identifier Type: OTHER

Identifier Source: secondary_id

RCAPHM21_0414

Identifier Type: -

Identifier Source: org_study_id