pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure

NCT02654327 | Unknown Phase 3 DMC

• 2 other identifiers: 15084DMcA-AS13/143/02
• Study Type: interventional
• Target: 1,120
• Locations: 1 country
• Sites: 1

Brief Summary

This is a trial of a new way of treating patients with respiratory failure. The investigators propose to deliver a multi-centre clinical trial to determine whether veno-venous extracorporeal carbon dioxide removal (VV-ECCO2R) and lower tidal volume mechanical ventilation improves outcomes and is cost-effective, in comparison with standard care in patients who are mechanically ventilated for acute hypoxaemic respiratory failure

Conditions

Acute Respiratory Failure With Hypoxia

Keywords

Extracorporeal; Acute Respiratory Distress Syndrome; Protective Lung Ventilation; Ventilator Induced Lung Injury; Carbon Dioxide Removal; Lung; Lung Injury

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  90 days after randomisation

Secondary Outcomes (12)

• Tidal volume (ml/kg Predicted Body Weight)

  day 2 and day 3 after randomisation

• Ventilator free days

  28 days after randomisation

• Duration of ventilation in survivors

  28 days after randomisation

• Need for Extracorporeal Membrane Oxygenation (ECMO)

  7 days after randomisation

• Mortality rate

  28 days, 6 months and 1 year after randomisation

Other Outcomes (1)

• Right Ventricular function

  Baseline & Day 2/Day 3

Study Arms (2)

Standard Care

NO INTERVENTION

Standard care with conventional lung protective mechanical ventilation

ECCO2R to enable lower tidal volume mechanical ventilation

EXPERIMENTAL

VV-ECCO2R to enable lower tidal volume mechanical ventilation (target tidal volume of ≤ 3ml/kg predicted body weight and a Pplat ≤ 25cmH20)

Device: VV-ECCO2R to enable lower tidal volume mechanical ventilation

Interventions

VV-ECCO2R to enable lower tidal volume mechanical ventilation DEVICE

In the intervention arm a dual lumen catheter will be inserted into a central vein. VV-ECCO2R is commenced and managed as per study manual. Tidal volumes are then reduced on mechanical ventilation to enable lower tidal volume ventilation. Lower tidal volume facilitated by VV-ECCO2R will continue for a least 2 days up to a maximum of 7 days

ECCO2R to enable lower tidal volume mechanical ventilation

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Invasive mechanical ventilation using positive end expiratory pressure (PEEP) ≥ 5cmH2O
• Acute and potentially reversible cause of acute respiratory failure as determined by the treating physician
• Within 48 hours of the onset of hypoxemia as defined by Pa02/Fi02 less than or equal to 20kPA

You may not qualify if:

• Age \< 16 years old
• Intubated and mechanically ventilated via an endotracheal or tracheostomy tube ≥ 7 days (168 hours) up to the time of randomisation
• Ability to maintain Vt to ≤ 3ml/kg PBW while maintaining pH ≥ 7.2 as determined by the treating physician
• Receiving, or decision to commence, ECMO in the next 24 hours
• Mechanical ventilation using high frequency oscillation ventilation or airway pressure release ventilation
• Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure
• Acute respiratory failure fully explained by left ventricular failure or fluid overload (May be determined by clinical assessment or echocardiography/cardiac output monitoring)
• Left ventricular failure requiring mechanical support
• Contra-indication to limited systemic anticoagulation with heparin
• Unable to obtain vascular access to a central vein (internal jugular or femoral vein)
• Consent declined
• Treatment withdrawal imminent within 24 hours
• Patients not expected to survive 90 days on basis of premorbid health status
• DNAR (Do Not Attempt Resuscitation) order (excluding advance directives) in place
• Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead
• Queen's University, Belfast: collaborator
• Northern Ireland Clinical Trials Unit: collaborator

Study Sites (1)

Belfast Health and Social Care Trust

Belfast, United Kingdom

Location

Related Publications (9)

• Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

  PMID: 10793162 BACKGROUND

• Fitzgerald M, Millar J, Blackwood B, Davies A, Brett SJ, McAuley DF, McNamee JJ. Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review. Crit Care. 2014 May 15;18(3):222. doi: 10.1186/cc13875.

  PMID: 25033302 BACKGROUND

• Terragni PP, Del Sorbo L, Mascia L, Urbino R, Martin EL, Birocco A, Faggiano C, Quintel M, Gattinoni L, Ranieri VM. Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology. 2009 Oct;111(4):826-35. doi: 10.1097/ALN.0b013e3181b764d2.

  PMID: 19741487 BACKGROUND

• Bein T, Weber-Carstens S, Goldmann A, Muller T, Staudinger T, Brederlau J, Muellenbach R, Dembinski R, Graf BM, Wewalka M, Philipp A, Wernecke KD, Lubnow M, Slutsky AS. Lower tidal volume strategy ( approximately 3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med. 2013 May;39(5):847-56. doi: 10.1007/s00134-012-2787-6. Epub 2013 Jan 10.

  PMID: 23306584 BACKGROUND

• Boyle AJ, Reddy K, Conlon J, Auzinger G, Bannard-Smith J, Barrett NA, Camporota L, Gillies MA, Jackson C, McDowell C, Patel B, Perkins GD, Szakmany T, Tunnicliffe W, Welters ID, McNamee JJ, McAuley DF, O'Kane CM. Evaluation of Plasma Biomarkers to Understand the Biology and Heterogeneity of Treatment Effect in Lower Tidal Volume Ventilation Facilitated by Extracorporeal CO2 Removal in Acute Hypoxemic Respiratory Failure: A Secondary Analysis of the REST Trial. Crit Care Explor. 2025 Mar 27;7(4):e1246. doi: 10.1097/CCE.0000000000001246. eCollection 2025 Apr 1.

  PMID: 40146037 DERIVED

• Agus A, McNamee JJ, Jackson C, McAuley DF. Extracorporeal carbon dioxide removal compared to ventilation alone in patients with acute hypoxaemic respiratory failure: cost-utility analysis of the REST RCT. Health Technol Assess. 2023 Aug;29(33):1-34. doi: 10.3310/FCDQ8036.

  PMID: 37843629 DERIVED

• Boyle AJ, McDowell C, Agus A, Logan D, Stewart JD, Jackson C, Mills J, McNamee JJ, McAuley DF. Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial. Thorax. 2023 Aug;78(8):767-774. doi: 10.1136/thorax-2022-218874. Epub 2022 Oct 5.

  PMID: 36198573 DERIVED

• McNamee JJ, Gillies MA, Barrett NA, Perkins GD, Tunnicliffe W, Young D, Bentley A, Harrison DA, Brodie D, Boyle AJ, Millar JE, Szakmany T, Bannard-Smith J, Tully RP, Agus A, McDowell C, Jackson C, McAuley DF; REST Investigators. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial. JAMA. 2021 Sep 21;326(11):1013-1023. doi: 10.1001/jama.2021.13374.

  PMID: 34463700 DERIVED

• Stokes JW, Gannon WD, Rice TW. Extracorporeal Carbon Dioxide Removal or Extracorporeal Membrane Oxygenation: Why Should We Care? Crit Care Med. 2021 May 1;49(5):e546-e547. doi: 10.1097/CCM.0000000000004844. No abstract available.

  PMID: 33854019 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Ventilator-Induced Lung Injury; Lung Injury

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Thoracic Injuries; Wounds and Injuries

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Intensive Care Medicine

Study Record Dates

• First Submitted: January 10, 2016
• First Posted: January 13, 2016
• Study Start: May 12, 2016
• Primary Completion: March 12, 2020
• Study Completion: April 30, 2022
• Last Updated: March 2, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)