Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO

NCT04832789 | Unknown DMC FDA Device

• 1 other identifier: ULTIMATE
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 11

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

Conditions

ARDS

Keywords

ECMO; Mechanical Ventilation; Ventilator-induced lung injury

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Ventilator-free days

  Up to 30 days

• Length of stay

  Through study completion, an average of 2 years

• Number of patients with non-pulmonary organ dysfunction

  Up to 30 days

• Number of patients with barotrauma

  Up to 30 days

• Mortality

  Through study completion, an average of 2 years

Study Arms (2)

Best conventional ventilation

NO INTERVENTION

Ultra-protective ventilation with ECMO

EXPERIMENTAL

Device: Venovenous ECMO

Interventions

Venovenous ECMO DEVICE

Venovenous ECMO

Ultra-protective ventilation with ECMO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Toronto: lead
• University Health Network, Toronto: collaborator

Study Sites (11)

New York Presbyterian Hospital

New York, New York, 10032, United States

Location

OHSU Hospital

Portland, Oregon, 97239, United States

Location

University of Alberta Hospital

Edmonton, Alberta, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

University of Ottawa

Ottawa, Ontario, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Unity Health

Toronto, Ontario, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Location

MeSH Terms

Conditions

Ventilator-Induced Lung Injury

Interventions

Extracorporeal Membrane Oxygenation

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Respiratory Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Niall Ferguson, MD, MSc

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Eddy Fan, MD, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathleen Exconde

CONTACT

416-340-4800; kathleen.exconde@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 28, 2021
• First Posted: April 6, 2021
• Study Start: June 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 6, 2021

Record last verified: 2021-04

Locations

US (2); CA (9)