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

Phase 3TerminatedNCT01522599

University of Turin, Italy230 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

230

Conditions

Acute Respiratory Distress Syndrome

Interventions

ARDS-Net StrategyOTHER

Treatment according to the ARDS-Net protocol (The Acute Respiratory Distress Syndrome Network N Engl J Med 2000; 342:1301-1308May 4, 2000)

ECCO2-ROTHER

Ventilation with Tidal Volume of 4 ml/kg PBW and low flow CO2 removal

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Turin - Department of Anesthesia and Intensive Care Medicine

Turin, Italy

Outcomes

Primary Outcomes

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.

Time frame: 28 DAYS

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Data from ClinicalTrials.gov

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