Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With ARDS and ECMO

Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With Severe Acute Respiratory Distress Syndrome and Extracorporeal Membrane Oxygenation: a Prospective, Randomized, Clinical Trial

The acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure, presented in 10% of all intensive care patients and carrying a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for patients with severe ARDS. Mechanical ventilator settings in patients with severe ARDS during ECMO therapy are not clearly defined at the moment.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Diseases; Lung Diseases; Extracorporeal Membrane Oxygenation; Respiratory Distress Syndrome; Acute Lung Injury; ARDS; Lung Injury, Acute
• Intervention / Treatment: Other: Ultra-protective ventilator settings; Other: Standard ventilator settings

Detailed Description

The aim of this study is to assess the effect of a rigorous low breathing frequency and ultra-low tidal volume ventilation strategy on clinical outcome, compared to standard ventilator settings following the recent guidelines in patients with severe ARDS treated with ECMO.

The hypothesis is that a low breathing frequency and ultra-low tidal volume ventilation strategy is more protective for the ARDS challenged lung and reduces the duration of mechanical ventilation and so increases the ventilator free days in patients with severe ARDS treated with ECMO.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna - Division of General Anaesthesia and Intensive Care Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderate to severe ARDS - Partial pressure of oxygen/Fraction of inspired oxygen (PaO2/FiO2) < 200 mmHg
• ECMO < 24 hours in situ
• Gender-matched
• Age-matched

Exclusion Criteria:

• BMI > 40
• Expected weaning of ECMO < 3 days (postoperative ECMO)
• Combustion
• Restrictive chest wall impairment
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intervention group; Ultra-protective ventilator settings in patients with ARDS and ECMO.	Other: Ultra-protective ventilator settings; 4-5 Breaths per minute; 14-16 cmH2O Positive endexpiratory pressure (PEEP) (adjust PEEP to 23 < Plateau pressure < 25 cmH2O); 23-25 cmH2O Plateau pressure (adjust to not exceed Tidal volume > 4 mL/kg Predicted body weight (PBW)); < 4mL/kg PBW Tidal volume; 1:5 Inspiration:Expiration (I:E)
ACTIVE_COMPARATOR: Control group; Standard ventilator settings in patients with ARDS and ECMO.	Other: Standard ventilator settings; 12-25 Breaths per minute; 8-12 cmH2O PEEP; max. 35 cmH2O Plateau pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator free days	Ventilator free days	Immediately after initiation of ECMO up to 28 days
Time from randomization to fulfillment of extubation criteria	Time from randomization (initiation of ECMO) to fulfillment of the extubation criteria: ARDS resolved; Temperature ≥ 36°C and ≤ 39°C; Low FiO2 (< 0.5); PEEP (< 8 cmH2O) requirement; Able to initiate spontaneous breaths; Tidalvolume > 5 mL/kg or > 325 mL; Minute ventilation 5-6 L/min; PaO2/FiO2 > 200 mmHg; pH ≥ 7.25; Ability to cough after deflating tube cuff; Respiratory rate 8-30/min; Hemodynamic stability	Immediately after initiation of ECMO up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total time of mechanical ventilation	Total time of mechanical ventilation	Start of mechanical ventilation up to 28 days
28 day mortality	Mortality from initiation of ECMO till day 28 after initiation of ECMO	Immediately after initiation of ECMO up to 28 days
One year mortality	Mortality from initiation of ECMO till one year after initiation of ECMO	Immediately after initiation of ECMO up to one year
Incidence of reintubation	Incidence of reintubation	Immediately after initiation of ECMO up to 28 days
Length of ICU stay	Length of ICU stay	Immediately after initiation of ECMO
Evaluation of RAS, ACE, ACE2.	Analyses of leftover blood. Renin angiotensin system (RAS) and Angiotensin converting enzyme (ACE) evaluation.	2 months
Evaluation of Cytokines in pg/ml	IL-6, IL-8, TNFR1, RAGE, Protein C	2 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Roman Ullrich, Ao.Univ.Prof., Department of Anesthesia and Intensive Care

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 6, 2018
• Primary Completion (ACTUAL): August 1, 2021
• Study Completion (ACTUAL): August 1, 2021

Study Registration Dates

• First Submitted: November 29, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (ACTUAL): December 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: ARDS, ECMO, Ventilation
• Additional Relevant MeSH Terms: Respiration Disorders; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Lung Diseases; Wounds and Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Respiratory Tract Diseases
• Other Study ID Numbers: MUVienna ARDS-ECMO

Drug and device information, study documents

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