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)

This study has been terminated.
(Financial hardship)
Sponsor:
Information provided by (Responsible Party):
Marco Ranieri, University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT01522599
First received: January 26, 2012
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Acute Respiratory Distress Syndrome
Other: ARDS-Net Strategy
Other: ECCO2-R
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • Number of ventilator-free days during the 28 days immediately after randomization [ Time Frame: 28 DAYS ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    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). [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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). [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days ] [ Designated as safety issue: No ]

    Weaning readiness will be defined if the following 4 criteria are met for the last 30 minutes during a spontaneous breathing trial (SBT).

    1. SpO2 ≥ 90% and / or PaO2 ≥ 60 mm Hg; PaO2 to take precedence if both available
    2. Respiratory Rate ≤ 35 / min
    3. pH ≥ 7.30
    4. No respiratory distress

  • Cumulative SOFA-free score between randomization and day 28. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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"


Enrollment: 230
Study Start Date: April 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Further protective ventilation

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522599

Locations
Italy
University of Turin - Department of Anesthesia and Intensive Care Medicine
Turin, Italy, 10126
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Marco Ranieri, Principal Investigator, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT01522599     History of Changes
Other Study ID Numbers: ELP-CEI315
Study First Received: January 26, 2012
Last Updated: June 16, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by University of Turin, Italy:
ARDS: Acute Respiratory Distress Syndrome
LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL
VILI: Ventilator Induced Lung Injury

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Wounds and Injuries
Ventilator-Induced Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries

ClinicalTrials.gov processed this record on July 20, 2014