Ultra-protective Pulmonary Ventilation Supported by Low Flow ECCO2R for Severe ARDS (U-Protect)

Ultra-protective Pulmonary Ventilation Supported by Low Flow Extracorporeal Carbon Dioxide Removal (ECCO2R) and Prone Positioning for ARDS; a Pilot Study.

This study evaluates the use of ultra-protective ventilation, where very low ventilation volumes are used, in patients with severe acute respiratory distress syndrome (ARDS) meeting criteria to nurse in the prone position. Half the patients will receive ultra-protective ventilation support by extracorporeal carbon dioxide removal, while the other half will receive conventional lung protective ventilation.

Study Overview

• Status: Terminated
• Conditions: Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Other: Conventional Lung Protective Ventilation; Device: Prismalung; Other: Ultra-protective ventilation

Detailed Description

Current best practices for management of severe ARDS include lung protective ventilation and nursing in the prone position. However, the best lung protective strategy is not currently established and using smaller ventilation volumes than standard lung protective ventilation suggest lung recovery is improved.

Application of smaller ventilation volumes requires extracorporeal carbon dioxide removal, using a device similar to a dialysis to remove carbon dioxide directly from the blood. One such device in the Prismalung, it removes blood through a catheter, much like a dialysis catheter, pumps it through a gas exchange cartridge which removes carbon dioxide. The gas exchange cartridge functions in a similar way to a dialysis filter, except it allow gases to pass through, unlike dialysis filters which allow passage of fluid and small molecules.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 609606
    • Ng Teng Fong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to MICU with respiratory failure and intubated
• ARDS criteria per Berlin definition
• PaO2:FiO2 ratio ≤ 200 mmHg for > 6 hours with FiO2 ≥0.5
• Expected to require mechanical ventilation for >48 hours
• Reversible disease

Exclusion Criteria:

• Anticoagulation contraindicated
• Proven HIT
• Unable to obtain central venous access
• Refractory hypoxia (PaO2:FiO2 ≤80 after recruitment and proning) or other indication for ECMO
• Home oxygen use
• Severe COPD
• Interstitial lung disease
• > 7 days of mechanical ventilation
• Immunocompromised patient (bone marrow, untreated HIV, PJP)
• Advanced malignancy with life expectancy ≤ 6months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional lung protective ventilation; Lung protective ventilation (6ml/kg predicted body weight). All other interventions per intensive care unit standardised ARDS management protocol	Other: Conventional Lung Protective Ventilation; Ventilation with 6ml/kg predicted body weight
Experimental: Ultra-protective ventilation; Ultra-protective ventilation (</= 3ml/kg predicted body weight) targeting plateau pressure of </= 25 cmH2O, supported by Prismalung. All other intervention per intensive care unit standardised ARDS management protocol	Device: Prismalung; Prism lung (Baxter Healthcare/Gambro Lund, Sweden) is an extracorporeal carbon dioxide removal device. It removes blood through a double lumen catheter and pumps it through a hollow fiber gas exchange cartridge which is impervious to fluid. Carbon dioxide diffuses out, down a concentration gradient which is maintained by sweep gas flowing through the centre of the hollow fibres. The decarboxylated blood is returned to the patient through the double lumen catheter.; Other Names: Low flow extracorporeal carbon dioxide removal; Respiratory Dialysis; Other: Ultra-protective ventilation; Ventilation with

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plateau Pressure	Ability to achieve a plateau pressure of </=25 cmH20 in the intervention arm	Duration of ventilation for severe ARDS, expected average time 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in ICU stay		Duration of patient stay in ICU, expected average stay 2 weeks
Length of hospital stay		Duration of patient stay in hospital
Mortality	ICU mortality, hospital mortality, 30 day, 60 day and 90 day mortality	Monitored for 3 months
Cardiac Imaging	Echocardiogram data will be collected before prone position, after prone positioning and following initiation of ultra-protective ventilation	One data set per patient during first 72 hours
Extracorporeal carbon dioxide removal related complications	Complications or adverse events related to ECCO2R and associated anticoagulation	Duration of severe ARDS, expected average time frame 10 days
Ventilator free days		28 days
All severe adverse events		Duration of ICU stay (anticipate average stay 1-2 weeks)
Number of patient meeting proning criteria in each group		Duration of ICU stay
Ability to successfully prone		Duration of ICU stay
Incidence of dialysis in ICU, and ability to successfully initiate		Duration of ICU stay
Incidence of referrals for ECMO		Duration of ICU stay
Rate and reasons for declining consent to study participation		First 48 hours
Enrolment rates		First 48 hours
Lung recruitability		Duration of ICU stay
Ventilation parameters	Data download from mechanical ventilation	Duration of mechanical ventilation
Ventilator associated pneumonia rates		Duration of ICU stay
Barotrauma complications		Duration of ICU stay
Biomarkers of Pulmonary Inflammation	Serum will be drawn and stored for pulmonary biomarkers analysis at the above time points	Day 0, 4 and 7

Collaborators and Investigators

• Sponsor: National University Health System, Singapore
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Matthew E Cove, MBChB, National University Health System

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2017
• Primary Completion (Actual): May 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: September 26, 2014
• First Posted (Estimate): September 29, 2014

Study Record Updates

• Last Update Posted (Actual): September 14, 2020
• Last Update Submitted That Met QC Criteria: September 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: NMRC/TA/0015/2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No