Back to resultsFlow-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)
Primary Purpose
Acute Respiratory Distress Syndrome
Status
Terminated
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
ARDS-Net Strategy
ECCO2-R
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring ARDS: Acute Respiratory Distress Syndrome, LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL, VILI: Ventilator Induced Lung Injury
Eligibility Criteria
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
Sites / Locations
- University of Turin - Department of Anesthesia and Intensive Care Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
ARDS-Net strategy (Control)
ECCO2-R with 4 mL/Kg Vt (Treatment)
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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
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.
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
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.
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"
Full Information
NCT ID
NCT01522599
First Posted
January 26, 2012
Last Updated
June 16, 2014
Sponsor
University of Turin, Italy
1. Study Identification
Unique Protocol Identification Number
NCT01522599
Brief Title
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
Acronym
ELP
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Terminated
Why Stopped
Financial hardship
Study Start Date
April 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Turin, Italy
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
ARDS: Acute Respiratory Distress Syndrome, LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL, VILI: Ventilator Induced Lung Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
230 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARDS-Net strategy (Control)
Arm Type
Active Comparator
Arm Title
ECCO2-R with 4 mL/Kg Vt (Treatment)
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
ARDS-Net Strategy
Other Intervention Name(s)
Protective ventilation
Intervention Description
Treatment according to the ARDS-Net protocol (The Acute Respiratory Distress Syndrome Network N Engl J Med 2000; 342:1301-1308May 4, 2000)
Intervention Type
Other
Intervention Name(s)
ECCO2-R
Other Intervention Name(s)
Further protective ventilation
Intervention Description
Ventilation with Tidal Volume of 4 ml/kg PBW and low flow CO2 removal
Primary Outcome Measure Information:
Title
Number of ventilator-free days during the 28 days immediately after randomization
Description
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.
Time Frame
28 DAYS
Secondary Outcome Measure Information:
Title
28-day all-cause mortality
Description
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.
Time Frame
28 days
Title
90-day all-cause mortality.
Description
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.
Time Frame
90 days
Title
Number of ICU-free days during the 28 days immediately after randomization (ICU-FD).
Description
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.
Time Frame
28 days
Title
Cumulative incidence of first episode of refractory hypoxemia (during 28 days after randomization).
Description
Refractory hypoxemia is defined as PaO2 < 60 mm Hg for at least 1 hour while receiving an FIO2 of 1.0
Time Frame
28 days
Title
Cumulative incidence of the use of rescue therapies.
Description
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.
Time Frame
28 days
Title
Cumulative incidence of first day that meet criteria for weaning readiness during 28 days after randomization.
Description
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
Time Frame
28 days
Title
Cumulative SOFA-free score between randomization and day 28.
Description
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.
Time Frame
28 days
Title
Cumulative incidence of severe adverse events during 28 days after randomization.
Description
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"
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vito Marco VM Ranieri, MD
Organizational Affiliation
Department of Anesthesia and Intensive Care Medicine, University of Turin, Italy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antonio A Pesenti, MD
Organizational Affiliation
Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy
Official's Role
Study Chair
Facility Information:
Facility Name
University of Turin - Department of Anesthesia and Intensive Care Medicine
City
Turin
ZIP/Postal Code
10126
Country
Italy
12. IPD Sharing Statement
Links:
URL
https://elp.ddmc.unito.it
Description
ELP STUDY e-CRF
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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
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