Clinical trial NCT01522599: 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
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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Keywords: ARDS: Acute Respiratory Distress Syndrome
LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL
VILI: Ventilator Induced Lung Injury
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2012-01-31
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Number of ventilator-free days during the 28 days immediately after randomization
timeFrame: 28 DAYS
Secondary outcomes:
measure: 28-day all-cause mortality
timeFrame: 28 days
measure: 90-day all-cause mortality.
timeFrame: 90 days
measure: Number of ICU-free days during the 28 days immediately after randomization (ICU-FD).
timeFrame: 28 days
measure: Cumulative incidence of first episode of refractory hypoxemia (during 28 days after randomization).
timeFrame: 28 days
measure: Cumulative incidence of the use of rescue therapies.
timeFrame: 28 days
measure: Cumulative incidence of first day that meet criteria for weaning readiness during 28 days after randomization.
timeFrame: 28 days
measure: Cumulative SOFA-free score between randomization and day 28.
timeFrame: 28 days
measure: Cumulative incidence of severe adverse events during 28 days after randomization.
timeFrame: 28 days
Other outcomes:
Locations:
city: Turin
country: Italy
facility: University of Turin - Department of Anesthesia and Intensive Care Medicine
Study officials:
affiliation: Department of Anesthesia and Intensive Care Medicine, University of Turin, Italy
name: Vito Marco VM Ranieri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy
name: Antonio A Pesenti, MD
role: STUDY_CHAIR
References: