Clinical trial NCT04832789: Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO
Official title: Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO (ULTIMATE) Pilot Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: ARDS
Keywords: ECMO
Mechanical Ventilation
Ventilator-induced lung injury
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2021-04-06
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Proportion of patients adhering to the study protocol
timeFrame: Through study completion, an average of 2 years
measure: Proportion of patients crossing over to VV ECMO
timeFrame: Through study completion, an average of 2 years
measure: Number of patients recruited for the study
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Ventilator-free days
timeFrame: Up to 30 days
measure: Length of stay
timeFrame: Through study completion, an average of 2 years
measure: Number of patients with non-pulmonary organ dysfunction
timeFrame: Up to 30 days
measure: Number of patients with barotrauma
timeFrame: Up to 30 days
measure: Mortality
timeFrame: Through study completion, an average of 2 years
measure: Health-related quality of life
timeFrame: At 6 months post-randomization
Other outcomes:
Locations:
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Portland
country: United States
facility: OHSU Hospital
state: Oregon
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Unity Health
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: University Health Network, Toronto
name: Niall Ferguson, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Eddy Fan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: