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Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO (ULTIMATE)

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ClinicalTrials.gov Identifier: NCT04832789
Recruitment Status : Not yet recruiting
First Posted : April 6, 2021
Last Update Posted : April 6, 2021
Sponsor:
Collaborator:
University Health Network, Toronto
Information provided by (Responsible Party):
Eddy Fan, University of Toronto

Study Description
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Brief Summary:

Primary Research Question for the Full ULTIMATE Randomized Clinical Trial (RCT): What is the effect of ultra-protective ventilation facilitated by extracorporeal membrane oxygenation (ECMO) versus best current conventional ventilation (CV) on all-cause hospital mortality among patients with early moderate-severe acute respiratory distress syndrome (ARDS)?

Secondary Research Questions: Among patients with early moderate-severe ARDS, what is the effect of ultra-protective ventilation versus CV on: (1) duration of mechanical ventilation; (2) duration of ICU and hospital stay; (3) organ dysfunction; (4) barotrauma; and (5) mortality at other time-points (ICU discharge, 28-day, 60-day)?

The ULTIMATE Pilot Study: Before embarking on a definitive multinational trial to address the questions listed above, the ULTIMATE Pilot Study has these 3 specific feasibility objectives:

  1. To assess adherence to our explicit mechanical ventilation protocols, with particular focus on delivered tidal volumes in both groups;
  2. To estimate the rate of patient recruitment and understand barriers to recruitment; and
  3. To measure and understand the reasons for crossovers or rescue by ECMO in the control group.

In addition, we will monitor safety issues, recording serious adverse events in both groups.


Condition or disease Intervention/treatment Phase
ARDS Device: Venovenous ECMO Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO (ULTIMATE) Pilot Randomized Trial
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : December 2023
Arms and Interventions
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Arm Intervention/treatment
No Intervention: Best conventional ventilation
Experimental: Ultra-protective ventilation with ECMO Device: Venovenous ECMO
Venovenous ECMO


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients adhering to the study protocol [ Time Frame: Through study completion, an average of 2 years ]
    Adherence to our explicit ventilation protocols will be adequate if more than 80% of patients have fewer than 10% of monitored values as major protocol violations

  2. Proportion of patients crossing over to VV ECMO [ Time Frame: Through study completion, an average of 2 years ]
    The number of protocol withdrawals or off-protocol treatment with VV ECMO will be acceptable if fewer than 10% of patients crossover or receive VV ECMO, when not allowed by the protocol

  3. Number of patients recruited for the study [ Time Frame: Through study completion, an average of 2 years ]
    Patient accrual will be adequate if we recruit 72 patients from 12 sites over 1 year of enrolment


Secondary Outcome Measures :
  1. Ventilator-free days [ Time Frame: Up to 30 days ]
    Duration of alive and free of invasive mechanical ventilation

  2. Length of stay [ Time Frame: Through study completion, an average of 2 years ]
    ICU and hospital length of stay in survivors and non-survivors

  3. Number of patients with non-pulmonary organ dysfunction [ Time Frame: Up to 30 days ]
    Using standard definitions

  4. Number of patients with barotrauma [ Time Frame: Up to 30 days ]
    New barotrauma

  5. Mortality [ Time Frame: Through study completion, an average of 2 years ]
    At ICU discharge and 30-days

  6. Health-related quality of life [ Time Frame: At 6 months post-randomization ]
    Health-related quality of life (EQ-5D) via telephone


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Endotracheal mechanical ventilation for ≤ 5 days
  3. Early moderate-severe ARDS (Berlin Definition) - all of the following conditions for ≤ 48 hours i. PaO2/FiO2 ≤200 with PEEP > 5 cmH2O ii. bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules iii. respiratory failure not fully explained by cardiac failure or fluid overload iv. within one week of a known insult of new or worsening respiratory symptoms

  4. ARDS severity criterion - either 1 of:

    1. PaO2/FiO2 ≤ 150 mm Hg, on PEEP ≥ 10 cm H2O and FiO2 ≥ 0.5

Exclusion Criteria:

  1. Currently receiving any form of ECMO (e.g., venovenous, venoarterial, or hybrid configuration)
  2. Chronic hypercapnic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting
  3. Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not CPAP
  4. Actual body weight exceeding 1 kg per centimeter of height
  5. Severe hypoxemia with PaO2/FiO2 < 80 mmHg
  6. Expected mechanical ventilation duration < 48 hours
  7. Treating team is in the process of moving to a palliative mode of care
  8. Moribund patient not expected to survive 24 hours despite ongoing life-sustaining therapies
  9. Confirmed diffuse alveolar hemorrhage from vasculitis
  10. Contraindications to limited anticoagulation (e.g., active GI bleeding, bleeding diathesis)
  11. Pregnancy - due to unknown effects of PaCO2 changes on placental blood flow
Contacts and Locations
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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): NCT04832789


Contacts
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Contact: Kathleen Exconde 416-340-4800 ext 5519 kathleen.exconde@uhn.ca

Locations
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United States, New York
New York Presbyterian Hospital
New York, New York, United States, 10032
Contact: TBA         
Principal Investigator: Daniel Brodie, MD         
United States, Oregon
OHSU Hospital
Portland, Oregon, United States, 97239
Contact: TBA         
Principal Investigator: Terri Hough, MD, MSc         
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada
Contact: TBA         
Principal Investigator: Sean Bagshaw, MD, MSc         
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada
Contact: TBA         
Principal Investigator: Karen Bosma, MD         
Principal Investigator: Dave Nagpal, MD         
University of Ottawa
Ottawa, Ontario, Canada
Contact: TBA         
Principal Investigator: Andrew Seely, MD         
Principal Investigator: Bernard McDonald, MD         
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Contact: TBA         
Principal Investigator: Laveena Munshi, MD, MSc         
University Health Network - Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Contact: Kathleen Exconde    416-340-4800 ext 5519    kathleen.exconde@uhn.ca   
Sub-Investigator: Shaf Keshavjee, MD, MSc         
Sub-Investigator: Marcelo Cypel, MD, MSc         
Sub-Investigator: Lorenzo Del Sorbo, MD         
Sub-Investigator: Ewan Goligher, MD, PhD         
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Contact: TBA         
Principal Investigator: Neill Adhikari, MD, MSc         
Unity Health
Toronto, Ontario, Canada
Contact: TBA         
Principal Investigator: Laurent Brochard, MD         
Principal Investigator: Jan Friedrich, MD, PhD         
University Health Network - Toronto Western Hospital
Toronto, Ontario, Canada
Contact: TBA         
Principal Investigator: Elizabeth Wilcox, MD, PhD         
Canada, Quebec
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, Canada
Contact: TBA         
Principal Investigator: Francois Lamotagne, MD, MSc         
Sponsors and Collaborators
University of Toronto
University Health Network, Toronto
Investigators
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Principal Investigator: Niall Ferguson, MD, MSc University Health Network, Toronto
Principal Investigator: Eddy Fan, MD, PhD University Health Network, Toronto
More Information
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Responsible Party: Eddy Fan, Associate Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT04832789    
Other Study ID Numbers: ULTIMATE
First Posted: April 6, 2021    Key Record Dates
Last Update Posted: April 6, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Eddy Fan, University of Toronto:
ECMO
Mechanical Ventilation
Ventilator-induced lung injury