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pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure (REST)

This study is currently recruiting participants.
Verified May 2017 by Professor Danny McAuley, Belfast Health and Social Care Trust
Sponsor:
ClinicalTrials.gov Identifier:
NCT02654327
First Posted: January 13, 2016
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Queen's University, Belfast
Northern Ireland Clinical Trials Unit
Information provided by (Responsible Party):
Professor Danny McAuley, Belfast Health and Social Care Trust
  Purpose
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

Condition Intervention Phase
Acute Respiratory Failure With Hypoxia Device: VV-ECCO2R to enable lower tidal volume mechanical ventilation Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure

Resource links provided by NLM:


Further study details as provided by Professor Danny McAuley, Belfast Health and Social Care Trust:

Primary Outcome Measures:
  • All cause mortality [ Time Frame: 90 days after randomisation ]

Secondary Outcome Measures:
  • Tidal volume (ml/kg Predicted Body Weight) [ Time Frame: day 2 and day 3 after randomisation ]
  • Ventilator free days [ Time Frame: 28 days after randomisation ]
  • Duration of ventilation in survivors [ Time Frame: 28 days after randomisation ]
  • Need for Extracorporeal Membrane Oxygenation (ECMO) [ Time Frame: 7 days after randomisation ]
  • Mortality rate [ Time Frame: 28 days, 6 months and 1 year after randomisation ]
  • Health Related Quality of Life [ Time Frame: 6 months and 1 year after randomisation ]
  • Adverse Event Rate [ Time Frame: 28 days ]
  • Health & Social Care Service costs [ Time Frame: 6 months and 1 year after randomisation ]
  • St George Respiratory Questionnaire [ Time Frame: 6 months and 1 year after randomisation ]
  • Need for home oxygen [ Time Frame: 6 months and 1 year after randomisation ]
  • Post Traumatic Stress Syndrome Questionnaire (PTSS-14) [ Time Frame: 1 year after randomisation ]
  • Montreal Cognitive Assessment (MoCA-BLIND) or AD8 Dementia Screening Interview (AD8) [ Time Frame: 1 year after randomisation ]

Estimated Enrollment: 1120
Study Start Date: March 2016
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard Care
Standard care with conventional lung protective mechanical ventilation
Experimental: ECCO2R to enable lower tidal volume mechanical ventilation
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
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

Detailed Description:

Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality. A significant proportion of affected patients will have the Acute Respiratory Distress Syndrome (ARDS). Mechanical ventilation is often required to provide adequate gas exchange and although it is life-saving in this setting, it is also now known to contribute to the morbidity and mortality in the condition. Ventilators delivering high pressures and volumes cause regional over distension in the injured lung resulting in further inflammation and non-cardiogenic pulmonary oedema. The release of inflammatory mediators from the damaged lung causes systemic inflammation leading to multi-organ failure and death.

The few interventions that have been shown to reduce the high mortality in these patients have targeted ventilator-induced lung injury (VILI). A landmark trial by the ARDSNet trials group found that ventilating patients with acute hypoxaemic respiratory failure secondary to ARDS with a lung protective strategy aiming for a reduced tidal volume of 6ml/kg predicted body weight (PBW) and a maximum end-inspiratory plateau pressure (Pplat) ≤ 30cmH2O decreased mortality from 40% (in the conventional arm treated with tidal volume less than 12ml/kg PBW) to 31%.

Extracorporeal carbon dioxide removal (ECCO2R) in association with mechanical ventilation offers a potentially attractive solution to permit tidal volume reduction to less than 6ml/kg PBW and to achieve low plateau pressures (< 25cmH2O). Using these extracorporeal circuits, carbon dioxide can be 'dialysed' out of the blood while the lungs are ventilated in a more protective manner. In recent years, more efficient veno-venous devices have become available. These have replaced arterio-venous devices and have the advantage of not requiring arterial puncture. These can achieve carbon dioxide removal with relatively low extracorporeal blood flows (0.4−1 l/min) requiring only a smaller dual lumen venous catheter. In addition these ECCO2R devices use more biocompatible materials making the device more resistant to clot formation and cause less platelet and clotting factor consumption. Therefore only minimal systemic anticoagulation is required which reduces the likelihood of bleeding complications. These devices are now comparable to renal dialysis equipment, which is routinely used safely as standard care in ICUs in the United Kingdom.

Together this highlights the need for a large randomised controlled trial to establish whether VV-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective ventilatory strategy and is associated with improved patient outcomes. Importantly, if there was no benefit, the trial would provide evidence to stop the widespread adoption of an expensive and ineffective or potentially harmful treatment in this setting.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 hyperaemia as defined by Partial Pressure Oxygen / Fraction of inspired oxygen ≤ 20kPa

Exclusion Criteria:

  • 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 in place
  • Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)
  • Severe chronic liver disease (Child Pugh >11)
  • Platelet count < 40,000 mm3
  • Previously enrolled in the REST trial
  • Prisoners
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02654327


Contacts
Contact: Danny F McAuley, MB BCh d.f.mcauley@qub.ac.uk
Contact: James J McNamee, MB BCh james.mcnamee@belfasttrust.hscni.net

Locations
United Kingdom
Belfast Health and Social Care Trust Recruiting
Belfast, United Kingdom
Contact: Danny McAuley    +442890 972144    d.f.mcauley@qub.a.uk   
Sponsors and Collaborators
Belfast Health and Social Care Trust
Queen's University, Belfast
Northern Ireland Clinical Trials Unit
  More Information

Publications:
Responsible Party: Professor Danny McAuley, Professor of Intensive Care Medicine, Belfast Health and Social Care Trust
ClinicalTrials.gov Identifier: NCT02654327     History of Changes
Other Study ID Numbers: 15084DMcA-AS
13/143/02 ( Other Grant/Funding Number: NIHR HTA )
First Submitted: January 10, 2016
First Posted: January 13, 2016
Last Update Posted: May 30, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Professor Danny McAuley, Belfast Health and Social Care Trust:
Extracorporeal
Acute Respiratory Distress Syndrome
Protective Lung Ventilation
Ventilator Induced Lung Injury
Carbon Dioxide Removal
Lung
Lung Injury

Additional relevant MeSH terms:
Respiratory Insufficiency
Hypoxia
Respiratory Distress Syndrome, Adult
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Lung Diseases