Flow-flow ECCO2-R and 4 ml/kg Tidal Volume vs. 6 ml/kg Tidal Volume to Enhance Protection From VILI in Acute Lung Injury (ELP)

Flow-flow ECCO2-R and 4 ml/kg Tidal Volume vs. 6 ml/kg Tidal Volume to Enhance Protection From Ventilator Induced Lung Injury in Acute Lung Injury (ELP)

The main objective of this randomized multicenter clinical trial is to test the hypothesis that further reduction of VT to 4mL/kg may enhance lung protection in patients with ARDS as compared to the conventional "ARDS-Net" ventilation. Control of PaCO2 in the ~4 ml/kg arm would be accomplished by LFPPV- ECCO2-R.

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: ARDS-Net Strategy; Other: ECCO2-R

Detailed Description

The trial will test the hypothesis that a VT of 4 ml/kg PBW combined with low flow CO2 removal improves outcome in patients with severe ARDS (PFs ≤ 200 and PEEP ≥ 10) compared to ventilation with a VT of 6 ml/kg PBW. The study will accrue a maximum of 230 patients over approximately 12-18 months.

PRIMARY END-POINT: Number of ventilator-free days (VFDs) during the 28 days immediately after randomization

SECONDARY END-POINTS: 28 and 90-day all-cause mortality; number of ICU-free days during the 28 days immediately after randomization; cumulative incidence of: first episode of refractory hypoxemia (during 28 days after randomization), use of rescue therapies, first day that meet criteria for weaning, SOFA-free and severe adverse events.

Patients in CONTROL will be treated according to a modified, simplified version of The ARDS-Network lung protective lower tidal volume. Patients in TREATMENT group will be treated according to the ARDS-Net protocol modified (VT reduced by 1 ml/kg PBW at intervals ≤ 2 hours until VT = 4ml/kg PBW and the use of low-flow CO2 removal with a Plateau Pressure Goal: ≤ 25 cm H2O).

• Study Type: Interventional
• Enrollment (Actual): 230
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Turin, Italy, 10126
    • University of Turin - Department of Anesthesia and Intensive Care Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 18 years
• are on invasive assisted breathing less then 48 hours
• less than 24 hours since diagnosis for ARDS: with PF<=200 and PEEP>=10, bilateral infiltrate on chest X-Ray and no clinical evidence of left atrial hypertension
• have a commitment to full support

Exclusion Criteria:

• intubation and mechanical ventilation (any form) for > 48 hours
• risk of systemic bleeding with anticoagulation
• acute brain injury
• body mass index > 40
• neuromuscular disease that impairs ability to ventilate without assistance
• severe chronic respiratory disease
• burns > 40% total body surface area
• malignancy or other irreversible disease or condition for which 6- month mortality is estimated to be greater than 50%
• allogeneic bone marrow transplant within the last 5 years
• chronic respiratory condition making patient respirator dependent
• patient, surrogate, or physician not committed to full support
• acute myocardial infarction or acute coronary syndrome within 30 days
• moribund patient: not expected to survive 24 hours
• no consent/inability to obtain consent
• patients receiving high frequency ventilation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ARDS-Net strategy (Control)	Other: ARDS-Net Strategy; Treatment according to the ARDS-Net protocol (The Acute Respiratory Distress Syndrome Network N Engl J Med 2000; 342:1301-1308May 4, 2000); Other Names: Protective ventilation
Experimental: ECCO2-R with 4 mL/Kg Vt (Treatment)	Other: ECCO2-R; Ventilation with Tidal Volume of 4 ml/kg PBW and low flow CO2 removal; Other Names: Further protective ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ventilator-free days during the 28 days immediately after randomization	VFDs is a composite endpoint. VFD to day 28 is defined as the number of days after initiating unassisted breathing to day 28 after randomization, assuming a patient survives for at least two consecutive calendar days after initiating nassisted breathing and remains free of assisted breathing. If a patient dies prior to day 28 or is still receiving assisted breathing at day 27, his/her VFDs will be zero.	28 DAYS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality	All patients will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28." For example, day zero is the day of randomization and day 1 is the next day and encompasses all events that occur midnight-to-midnight, etc.	28 days
90-day all-cause mortality.	All patients will be classified as either "alive at Study Day 90" or, if dead, "dead at Study Day 90. Patients alive in hospital or in any health care facility at day 90 will be considered to have survived.	90 days
Number of ICU-free days during the 28 days immediately after randomization (ICU-FD).	ICU-FDs are defined as the number of days from the time of ICU discharge to day 28 after randomization, assuming survival for at least two consecutive calendar days after ICU discharge and continued stay outside the ICU setting to day 28. If a patient returns to the ICU and subsequently needs ICU admission to day 28, ICU-FDs will be counted from the end of the last period of ICU discharge to day 28.	28 days
Cumulative incidence of first episode of refractory hypoxemia (during 28 days after randomization).	Refractory hypoxemia is defined as PaO2 < 60 mm Hg for at least 1 hour while receiving an FIO2 of 1.0	28 days
Cumulative incidence of the use of rescue therapies.	The first day inhaled nitric oxide or prone position or high-frequency oscillation or high-frequency oscillatory ventilation or extracorporeal membrane oxygenation or any combinations of these therapies will be tabulated.	28 days
Cumulative incidence of first day that meet criteria for weaning readiness during 28 days after randomization.	Weaning readiness will be defined if the following 4 criteria are met for the last 30 minutes during a spontaneous breathing trial (SBT).; SpO2 ≥ 90% and / or PaO2 ≥ 60 mm Hg; PaO2 to take precedence if both available; Respiratory Rate ≤ 35 / min; pH ≥ 7.30; No respiratory distress	28 days
Cumulative SOFA-free score between randomization and day 28.	The SOFA-free score is calculated as the maximum daily score, minus the observed SOFA score. To monitor the degree of variation of the patient's SOFA score (as improvement or worsening) the daily difference between the maximum score and the observed score will be summed up for each day between randomization and day 28. Patients dying before the 28th day cannot continue to increase their cumulative SOFA-free score. In this way, the larger the cumulative score reached, the higher is the improvement of the patient and the probability of being alive at day 28.	28 days
Cumulative incidence of severe adverse events during 28 days after randomization.	Adverse events that are considered to be related to ECCO2-R and that follows a reasonable temporal sequence from the ECCO2-R and that could readily have been produced by ECCO2-R will be classified as: "DEVICE RELATED" or "PATIENT RELATED"	28 days

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Investigators: Principal Investigator: Vito Marco VM Ranieri, MD, Department of Anesthesia and Intensive Care Medicine, University of Turin, Italy; Study Chair: Antonio A Pesenti, MD, Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy

Publications and helpful links

Helpful Links

• ELP STUDY e-CRF

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: January 26, 2012
• First Submitted That Met QC Criteria: January 26, 2012
• First Posted (Estimate): January 31, 2012

Study Record Updates

• Last Update Posted (Estimate): June 17, 2014
• Last Update Submitted That Met QC Criteria: June 16, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: ARDS: Acute Respiratory Distress Syndrome; LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL; VILI: Ventilator Induced Lung Injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Ventilator-Induced Lung Injury
• Other Study ID Numbers: ELP-CEI315