ARDSULTIMATENCT04832789
Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO
A study testing Venovenous ECMO in people with ARDS, run by University of Toronto at 11 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS
- What is being tested?
- Venovenous ECMO
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Jun 2021to Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Endotracheal mechanical ventilation for ≤ 5 days
- 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
- ARDS severity criterion - either 1 of:
- PaO2/FiO2 ≤ 150 mm Hg, on PEEP ≥ 10 cm H2O and FiO2 ≥ 0.5
Who cannot join
- Currently receiving any form of ECMO (e.g., venovenous, venoarterial, or hybrid configuration)
- Chronic hypercapnic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting
- Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not CPAP
- Actual body weight exceeding 1 kg per centimeter of height
- Severe hypoxemia with PaO2/FiO2 < 80 mmHg
- Expected mechanical ventilation duration < 48 hours
Show all 11Show fewer
- Treating team is in the process of moving to a palliative mode of care
- Moribund patient not expected to survive 24 hours despite ongoing life-sustaining therapies
- Confirmed diffuse alveolar hemorrhage from vasculitis
- Contraindications to limited anticoagulation (e.g., active GI bleeding, bleeding diathesis)
- Pregnancy - due to unknown effects of PaCO2 changes on placental blood flow
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
Canada9 sites
University of Alberta Hospital
Edmonton, Alberta
TBA
Sean Bagshaw, MD, MSc
London Health Sciences Centre
London, Ontario
TBA
Karen Bosma, MD
University of Ottawa
Ottawa, Ontario
TBA
Andrew Seely, MD
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec
TBA
Francois Lamotagne, MD, MSc
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
TBA
Laveena Munshi, MD, MSc
University Health Network - Toronto General Hospital
Toronto, Ontario, M5G 2N2
Kathleen Exconde, 416-340-4800 ext. 5519, kathleen.exconde@uhn.ca
Shaf Keshavjee, MD, MSc
Sunnybrook Health Sciences Centre
Toronto, Ontario
TBA
Neill Adhikari, MD, MSc
Unity Health
Toronto, Ontario
TBA
Laurent Brochard, MD
University Health Network - Toronto Western Hospital
Toronto, Ontario
TBA
Elizabeth Wilcox, MD, PhD
United States2 sites
New York Presbyterian Hospital
New York, New York, 10032
TBA
Daniel Brodie, MD
OHSU Hospital
Portland, Oregon, 97239
TBA
Terri Hough, MD, MSc
About this study
Official title: 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)?
Read more
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:
- To assess adherence to our explicit mechanical ventilation protocols, with particular focus on delivered tidal volumes in both groups;
- To estimate the rate of patient recruitment and understand barriers to recruitment; and
- 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.
- Conditions
- ARDS
- Being tested
- Venovenous ECMO
- Keywords
- ECMO, Mechanical Ventilation, Ventilator-induced lung injury
- Medical subject headings
- Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venovenous ECMODevice
Venovenous ECMO
| Study group | Role | What they receive |
|---|---|---|
| Best conventional ventilation | No intervention | Not described |
| Ultra-protective ventilation with ECMO | Experimental | Not described Receives: Device: Venovenous ECMO |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: Through study completion, an average of 2 years
Secondary outcomes (6)
Ventilator-free days
Duration of alive and free of invasive mechanical ventilation
Measured: Up to 30 days
Length of stay
ICU and hospital length of stay in survivors and non-survivors
Measured: Through study completion, an average of 2 years
Number of patients with non-pulmonary organ dysfunction
Using standard definitions
Measured: Up to 30 days
Number of patients with barotrauma
New barotrauma
Measured: Up to 30 days
Mortality
At ICU discharge and 30-days
Measured: Through study completion, an average of 2 years
Health-related quality of life
Health-related quality of life (EQ-5D) via telephone
Measured: At 6 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study startJun 2021 (estimated)
- Primary completionJun 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto
- Responsible party
- Principal investigator, Eddy Fan, University of Toronto
- Investigators
- Niall Ferguson, MD, MSc, Principal investigator, University Health Network, TorontoEddy Fan, MD, PhD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04832789
- Sponsor's protocol ID
- ULTIMATE
- Acronym
- ULTIMATE
- Status last verified
- Apr 2021
- First submitted
- 28 Mar 2021
- Last updated
- 6 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO (ULTIMATE) Pilot Randomized Trial
- ClinicalTrials.gov ID
- NCT04832789
- Acronym / sponsor ID
- ULTIMATE / ULTIMATE
- Conditions
- ARDS
- Keywords
- ECMO, Mechanical Ventilation, Ventilator-induced lung injury
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Collaborators
- University Health Network, Toronto
- Study start
- Jun 2021 (estimated)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 6 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To assess adherence to our explicit mechanical ventilation protocols, with particular focus on delivered tidal volumes in both groups;
- To estimate the rate of patient recruitment and understand barriers to recruitment; and
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Best conventional ventilation | No intervention | – |
| Ultra-protective ventilation with ECMO | Experimental | Device: Venovenous ECMO |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years
- Endotracheal mechanical ventilation for ≤ 5 days
- 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
- ARDS severity criterion - either 1 of:
Key exclusion criteria (11 listed)
- Currently receiving any form of ECMO (e.g., venovenous, venoarterial, or hybrid configuration)
- Chronic hypercapnic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting
- Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not CPAP
- Actual body weight exceeding 1 kg per centimeter of height
- Severe hypoxemia with PaO2/FiO2 < 80 mmHg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Venovenous ECMOVenovenous ECMO | Device | Ultra-protective ventilation with ECMO |
Primary outcome
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
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
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
6 secondary outcomes
Ventilator-free days
Time frame: Up to 30 days
Length of stay
Time frame: Through study completion, an average of 2 years
Number of patients with non-pulmonary organ dysfunction
Time frame: Up to 30 days
Number of patients with barotrauma
Time frame: Up to 30 days
Mortality
Time frame: Through study completion, an average of 2 years
Health-related quality of life
Time frame: At 6 months post-randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niall Ferguson, MD, MSc principal investigator
University Health Network, Toronto
Eddy Fan, MD, PhD principal investigator
University Health Network, Toronto
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Venovenous ECMO in people with ARDS, run by University of Toronto at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kathleen Exconde (416-340-4800 ext. 5519, kathleen.exconde@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients adhering to the study protocol (time frame: Through study completion, an average of 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.