Cardinality Matching Study of Early v.s. Delayed VV ECMO in Severe Respiratory Failure

Clinical reasoning and recent data suggest that early use of venovenous extracorporeal membrane oxygenation in refractory respiratory failure may confer a survival advantage.

This retrospective matched study will assess whether patients who received VV ECMO at less severe hypoxaemia had differing outcomes to those who received ECMO with very severe hypoxaemia.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Failure; ECMO

Detailed Description

VV ECMO is increasingly used in refractory respiratory failure. Despite advances in lung protective ventilation strategies, patients who have severe respiratory failure often develop complications from mechanical ventilation, including volutrauma and barotrauma. ECMO allows gas exchange to occur extracorporeally and may reduce the potential burden of iatrogenic lung injury by allowing a reduction of volume and pressure support - a 'lung rest' strategy. It is theorised that earlier intitiation of ECMO may allow for better outcomes, as there will have been less time for iatrogenic lung injury to occur.

The UK ECMO registry has been collected of patients treated under the NHS England commissioned respiratory ECMO service since 2011. This study has been previously registered and publication is intended shortly.

Patients will be extracted from this registry if they received VV ECMO. Propensity matching scores will be created and patients will be stratified into groups of 'early' vs 'delayed' ECMO, based on their probability of being in either group.

Patients will be divided into cohorts based on the median PaO2/FiO2 ratio at decision to cannulate ('less severe hypoxaemia') and ('very severe hypoxaemia'). Matched cohorts will be created correcting for key confounding factors (age, primary diagnosis, duration of pre-ECMO ventilation and PaCO2), using cardinality matching (a novel technique described by Zubizaretta et al. in 2014) and traditional propensity-score-based methods.

The technique with greater balance and statistical power (as defined by sample size) will be selected for the primary analysis.

Further analyses will assess the relationship between hypoxaemia at decision-to-cannulate and confounding factors as above.

• Study Type: Observational
• Enrollment (Actual): 667

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a prespecified secondary analysis of the UK ECMO registry. Inclusion criteria are ultimately at the discretion of each recruiting centre, but includes adult patients with potentially reversible acute respiratory failure without absolute contraindications to ECMO therapy.

Description

Inclusion Criteria:

• Patients included in the UK ECMO registry (see previous registration; NCT number awaited; protocol ECMO-001)
• Patients with VV ECMO

Exclusion Criteria:

• Patients with inadequate or missing data for creation of propensity score models.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
'Less severe hypoxaemia'; PaO2/FiO2 ratio > 68 mmHg (9.1kPa) at decision-to-cannulate
'Very severe hypoxaemia'; PaO2/FiO2 ratio ≤ 68 mmHg (9.1kPa) at decision-to-cannulate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival to ECMO ICU discharge	Percentage of patients alive at discharge from the ICU at the specialist ECMO centre	Up to 90 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of ECMO treatment	Duration spent supported by active ECMO treatment.	Up to 90 days.

Collaborators and Investigators

• Sponsor: University of Cambridge

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2011
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): March 31, 2018

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 6, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: ECMO-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Access to IPD is via the UK ECMO network steering group. Enquiries in the first instance can be made to Dr Alain Vuylsteke, at a.vuylsteke@nhs.net

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No