Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO

ARDS Clinical Trial

— ULTIMATE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04832789
• Other study ID #: ULTIMATE
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2021
• Est. completion date: December 2023

Study information

• Verified date: April 2021
• Source: University of Toronto
• Contact: Kathleen Exconde
• Phone: 416-340-4800
• Email: kathleen.exconde[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 72
• Est. completion date: December 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ARDS

Intervention

Device:
• Venovenous ECMO
Venovenous ECMO

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	University of Ottawa	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Unity Health	Toronto	Ontario
Canada	University Health Network - Toronto General Hospital	Toronto	Ontario
Canada	University Health Network - Toronto Western Hospital	Toronto	Ontario
United States	New York Presbyterian Hospital	New York	New York
United States	OHSU Hospital	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
University of Toronto	University Health Network, Toronto

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

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