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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: ARDS
• Intervention / Treatment: Device: Venovenous ECMO

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kathleen Exconde; Phone Number: 5519 416-340-4800; Email: kathleen.exconde@uhn.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta Hospital
      • Contact: TBA
      • Principal Investigator: Sean Bagshaw, MD, MSc
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Centre
      • Principal Investigator: Dave Nagpal, MD
      • Contact: TBA
      • Principal Investigator: Karen Bosma, MD
    • Ottawa, Ontario, Canada
      • University of Ottawa
      • Contact: TBA
      • Principal Investigator: Andrew Seely, MD
      • Principal Investigator: Bernard McDonald, MD
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
      • Contact: TBA
      • Principal Investigator: Laveena Munshi, MD, MSc
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
      • Contact: TBA
      • Principal Investigator: Neill Adhikari, MD, MSc
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network - Toronto General Hospital
      • Contact: Kathleen Exconde; Phone Number: 5519 416-340-4800; Email: kathleen.exconde@uhn.ca
      • Sub-Investigator: Shaf Keshavjee, MD, MSc
      • Sub-Investigator: Marcelo Cypel, MD, MSc
      • Sub-Investigator: Ewan Goligher, MD, PhD
    • Toronto, Ontario, Canada
      • University Health Network - Toronto Western Hospital
      • Contact: TBA
      • Principal Investigator: Elizabeth Wilcox, MD, PhD
    • Toronto, Ontario, Canada
      • Unity Health
      • Contact: TBA
      • Principal Investigator: Laurent Brochard, MD
      • Principal Investigator: Jan Friedrich, MD, PhD
  • Quebec
    • Sherbrooke, Quebec, Canada
      • Centre Hospitalier Universitaire de Sherbrooke
      • Contact: TBA
      • Principal Investigator: Francois Lamotagne, MD, MSc
• United States
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital
      • Contact: TBA
      • Principal Investigator: Daniel Brodie, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Hospital
      • Contact: TBA
      • Principal Investigator: Terri Hough, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Best conventional ventilation
Experimental: Ultra-protective ventilation with ECMO	Device: Venovenous ECMO; Venovenous ECMO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients adhering to the study protocol	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	Through study completion, an average of 2 years
Proportion of patients crossing over to VV ECMO	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	Through study completion, an average of 2 years
Number of patients recruited for the study	Patient accrual will be adequate if we recruit 72 patients from 12 sites over 1 year of enrolment	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days	Duration of alive and free of invasive mechanical ventilation	Up to 30 days
Length of stay	ICU and hospital length of stay in survivors and non-survivors	Through study completion, an average of 2 years
Number of patients with non-pulmonary organ dysfunction	Using standard definitions	Up to 30 days
Number of patients with barotrauma	New barotrauma	Up to 30 days
Mortality	At ICU discharge and 30-days	Through study completion, an average of 2 years
Health-related quality of life	Health-related quality of life (EQ-5D) via telephone	At 6 months post-randomization

Collaborators and Investigators

• Sponsor: University of Toronto
• Collaborators: University Health Network, Toronto
• Investigators: Principal Investigator: Eddy Fan, MD, PhD, University Health Network, Toronto; Principal Investigator: Niall Ferguson, MD, MSc, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 28, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 1, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: ECMO; Mechanical Ventilation; Ventilator-induced lung injury
• Other Study ID Numbers: ULTIMATE

Drug and device information, study documents

• 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