Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO

Study Overview
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Brief Summary
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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.

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

Conditions
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ARDS

Intervention / Treatment
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* Device: Venovenous ECMO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Best conventional ventilation<br> | |
| Experimental: Ultra-protective ventilation with ECMO<br> | Device: Venovenous ECMO<br>* Venovenous ECMO<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, Mechanical Ventilation, Ventilator-induced lung injury