Acute Respiratory Distress SyndromePhase 3ELPNCT01522599
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
A Phase 3 study testing ARDS-Net Strategy and ECCO2-R in people with Acute Respiratory Distress Syndrome, run by University of Turin, Italy at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- ARDS-Net Strategy and ECCO2-R
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2012to Jan 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
University of Turin - Department of Anesthesia and Intensive Care Medicine
Turin, 10126
About this study
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)
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.
Read the 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).
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- ARDS-Net Strategy, ECCO2-R
- Keywords
- ARDS: Acute Respiratory Distress Syndrome, LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL, VILI: Ventilator Induced Lung Injury
- Medical subject headings
- Respiratory Distress Syndrome, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARDS-Net StrategyOther
Also called Protective ventilation
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
Also called Further protective ventilation
Ventilation with Tidal Volume of 4 ml/kg PBW and low flow CO2 removal
| Study group | Role | What they receive |
|---|---|---|
| ARDS-Net strategy (Control) | Active comparator | Not described Receives: Other: ARDS-Net Strategy |
| ECCO2-R with 4 mL/Kg Vt (Treatment) | Experimental | Not described Receives: Other: ECCO2-R |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 DAYS
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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"
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2012 (estimated)
- Study startApr 2012
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Financial hardship
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Ranieri, University of Turin, Italy
- Investigators
- Vito Marco VM Ranieri, MD, Principal investigator, Department of Anesthesia and Intensive Care Medicine, University of Turin, ItalyAntonio A Pesenti, MD, Study chair, Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522599
- Sponsor's protocol ID
- ELP-CEI315
- Acronym
- ELP
- Status last verified
- Jun 2014
- First submitted
- 26 Jan 2012
- Last updated
- 17 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01522599
- Acronym / sponsor ID
- ELP / ELP-CEI315
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- ARDS: Acute Respiratory Distress Syndrome, LOW FLOW ECCO2-R: EXTRA-CORPOREAL CO2 REMOVAL, VILI: Ventilator Induced Lung Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Financial hardship
- Enrolment
- 230 participants (actual)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 31 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARDS-Net strategy (Control) | Active comparator | Other: ARDS-Net Strategy |
| ECCO2-R with 4 mL/Kg Vt (Treatment) | Experimental | Other: ECCO2-R |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARDS-Net StrategyAlso: Protective ventilationTreatment according to the ARDS-Net protocol (The Acute Respiratory Distress Syndrome Network N Engl J Med 2000; 342:1301-1308May 4, 2000) | Other | ARDS-Net strategy (Control) |
| ECCO2-RAlso: Further protective ventilationVentilation with Tidal Volume of 4 ml/kg PBW and low flow CO2 removal | Other | ECCO2-R with 4 mL/Kg Vt (Treatment) |
Primary outcome
Number of ventilator-free days during the 28 days immediately after randomization
Time frame: 28 DAYS
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.
8 secondary outcomes
28-day all-cause mortality
Time frame: 28 days
90-day all-cause mortality.
Time frame: 90 days
Number of ICU-free days during the 28 days immediately after randomization (ICU-FD).
Time frame: 28 days
Cumulative incidence of first episode of refractory hypoxemia (during 28 days after randomization).
Time frame: 28 days
Cumulative incidence of the use of rescue therapies.
Time frame: 28 days
Cumulative incidence of first day that meet criteria for weaning readiness during 28 days after randomization.
Time frame: 28 days
Cumulative SOFA-free score between randomization and day 28.
Time frame: 28 days
Cumulative incidence of severe adverse events during 28 days after randomization.
Time frame: 28 days
Results and safety
The study was stopped early (reason given: Financial hardship). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vito Marco VM Ranieri, MD principal investigator
Department of Anesthesia and Intensive Care Medicine, University of Turin, Italy
Antonio A Pesenti, MD study chair
Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ARDS-Net Strategy and ECCO2-R in people with Acute Respiratory Distress Syndrome, run by University of Turin, Italy at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Financial hardship). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of ventilator-free days during the 28 days immediately after randomization (time frame: 28 DAYS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2014.