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Acute Lung InjuryNCT00750204

Airway Pressure Release Ventilation in Acute Lung Injury

A study testing APRV and Conventional MV in people with Acute Lung Injury and Acute Respiratory Distress Syndrome, run by Johns Hopkins University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to compare airway pressure release ventilation (APRV) to conventional mechanical ventilation (MV) in patients with acute lung injury (ALI) to determine if APRV can reduce agitation, delirium, and requirements for sedative medications. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APRV and Conventional MV
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Jul 2008to 15 Oct 2008
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Acute onset of:
  • Arterial Pressure of Oxygen (PaO2) / FiO2 ≤ 300
  • Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asymmetric
  • Requirement for positive pressure ventilation via endotracheal tube, and
  • No clinical evidence of left atrial hypertension.
  • Receiving conventional MV, or lung-protective ventilation (LPV), in the assist control (AC) mode with positive end-expiratory pressure (PEEP) > 5 cm H2O Criteria 1-3 must occur within a 24-hour period. "Acute onset" is defined as follows: the duration of the hypoxemia criterion (#1) and the chest radiograph criterion (#2) must be < 7 days at the time of randomization.

Who cannot join

  • FiO2 > 70% or PaO2/FiO2 < 125 or arterial pH < 7.25
  • Greater than 6 days since all inclusion criteria are met
  • Anticipated to begin weaning from MV within 48 hours
  • Neuromuscular disease that prevents the ability to generate spontaneous tidal volumes.
  • Glasgow Coma Scale (GCS) < 15 within 1 week of intubation
  • Acute stroke (vascular occlusion or hemorrhage)
Show all 22Show fewer
  • Current alcoholism or previous daily use of opioids or benzodiazepines before hospitalization
  • Acute meningitis or encephalitis
  • Pregnancy (negative pregnancy test required for women of child-bearing potential) or breast-feeding.
  • Severe chronic respiratory disease
  • Previous barotraumas during the current hospitalization
  • Clinical evidence of bronchoconstriction on bedside examination (i.e., wheezing).
  • Patient, surrogate, or physician not committed to full support
  • Severe chronic liver disease (Child-Pugh Score B or C)
  • International Normalized Ratio (INR) > 2.0
  • Platelet level < 50,000
  • Mean arterial pressure < 65, or patient receiving intravenous vasopressors (any dose of epinephrine, norepinephrine, phenylephrine, or dopamine > 5 mcg/kg/min)
  • Age < 16 years old
  • Morbid obesity (greater than 1kg/cm body weight).
  • No consent/inability to obtain consent
  • Unwillingness of the clinical team to use conventional low tidal-volume protocol for MV.
  • Moribund patient not expected to survive 24 hours.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Johns Hopkins Hospital Medical Intensive Care Unit

    Baltimore, Maryland, 21205

Other trials in United States

About this study

The purpose of this study is to compare airway pressure release ventilation (APRV) to conventional mechanical ventilation (MV) in patients with acute lung injury (ALI) to determine if APRV can reduce agitation, delirium, and requirements for sedative medications. We will also compare markers of inflammation in the blood and lung to determine if APRV reduces ventilator-induced lung injury (VILI), compared to conventional mechanical ventilation.

The proposed study is a randomized, crossover trial. We plan to enroll 40 patients with ALI and randomize to APRV or conventional MV for 24 hours. After this time the patients will be switched to the alternative mode of ventilation (MV or APRV) for another 24 hours. To assess breathing comfort, at the end of each 24-hour period we will measure the amounts of sedative and analgesic medications used. We will also measure the concentrations of markers of inflammation in the blood and lung as measures of VILI. Finally, throughout the study we will compare the adequacy of gas exchange with APRV compared to conventional MV.

Read the detailed description

Acute respiratory failure is common in patients with acute lung injury. MV re-establishes adequate gas exchange; it allows time for administration of antibiotics, for the host's immune system to fight infections, and for natural healing. Approximately 60% of ALI patients survive to hospital discharge (1). However, conventional approaches to MV in ALI frequently cause dyssynchrony between a patient's spontaneous respiratory efforts and the ventilator's respiratory cycle (2;3). Dyssynchrony causes discomfort, anxiety, and agitation. To manage dyssynchrony, physicians frequently prescribe large doses of sedative and analgesic medications. These medications contribute to delirium and sleep deprivation during the critical illness, and may delay weaning from MV and discharge from the intensive care unit (2;4). They may also contribute significantly to neuromuscular and neurocognitive sequelae after recovery from ALI (5;6). Moreover, MV may itself cause additional lung injury (ventilator-induced lung injury, VILI) which could, paradoxically, delay or prevent recovery from respiratory failure in some ALI patients (7;9).

Airway pressure release ventilation (APRV) is a mode of MV that is designed to reduce patient-ventilator dyssynchrony and VILI. It differs from most other modes of MV in that it allows patients to breathe spontaneously at any time, independent of the ventilator's cycle. This feature may improve breathing comfort by minimizing patient-ventilator dyssynchrony. Improving comfort and reducing agitation may ultimately curtail the use of sedative and analgesic medications. Since a substantial proportion of ventilation results from the patient's spontaneous efforts independent of the ventilator cycle, the frequency of mechanically assisted breaths can be reduced. This may reduce VILI from the cyclic opening-closing of alveoli and small bronchioles that results from assisted MV breaths. Another feature of APRV that distinguishes it from other modes of MV is that it applies a sustained high pressure during inspiration and a brief period of lower pressure during exhalation. This approach may maximize and maintain alveolar recruitment throughout the ventilatory cycle while limiting high airway pressures, thus further reducing VILI. Moreover, spontaneous contractions of the diaphragm during APRV may open dependent atelectatic lung regions, improving ventilation-perfusion (V/Q) matching and gas exchange. However, these potential advantages of APRV are unproven.

Being tested
APRV, Conventional MV
Keywords
Acute Lung Injury, ALI, Acute Respiratory Distress Syndrome, Mechanical Ventilation, Sedation, Critical Illness, Ventilator Induced Lung Injury, VILI, Cytokines, Protective Ventilation, Airway Pressure Release Ventilation, APRV, Breathing Comfort, Dyssynchrony, Asynchrony
Medical subject headings
Acute Lung Injury, Respiratory Distress Syndrome, Critical Illness, Ventilator-Induced Lung Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APRVDevice

    Also called Lung-protective ventilation, Airway Pressure Release Ventilation

    APRV Protocol

    • Set fraction of inspired oxygen (FiO2) at 0.1 higher than the setting on conventional MV currently used
    • Tlow = 1.0 second (this setting shall remain unchanged throughout the trial).
    • Respiratory rate (RR) to equal 60-65% of RR on conventional MV.
    • P high = the inspiratory plateau pressure. Maximum P high = 30 cm H20.
    • Plow = 5 cm water (H2O). Adjust Plow to achieve pressure release volumes 5.5-6.5 ml/kg of percent body weight (PBW).
    • If release volumes on APRV are greater than desired, increase Plow by 2-4 cm H2O increments to a maximum of Plow = 12 cm H2O. If release volumes are larger than desired despite raising Plow to 12 cm H20, decrease P high in increments of 2-4 cm H20 to achieve desired release volumes (minimum P high = 12 cm H20). If release volumes on APRV still remain larger than desired,the participant will be excluded from the study and placed on conventional MV.
  • Conventional MVDevice

    Also called Lung protective ventilation, conventional mechanical ventilation

    Low tidal-volume mechanical ventilation

Study groups in NCT00750204
Study groupRoleWhat they receive
APRVExperimentalPatients will be randomized to either arm. After 24 hours they will crossover to the alternative arm of the study for an additional 24 hours. After a total of 48 hours (24 hours in each study arm) the study will conclude.
Receives: Device: APRV
Conventional MVActive comparatorPatients will be randomized to either arm. After 24 hours they will crossover to the alternative arm of the study for an additional 24 hours. After a total of 48 hours (24 hours in each study arm) the study will conclude.
Receives: Device: Conventional MV

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Amount of Sedatives Used

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2008 (estimated)
  2. Study startJul 2008
  3. Primary completion15 Oct 2008
  4. Study completion15 Oct 2008

Why it stopped: slow recruitment

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00750204
Sponsor's protocol ID
NA_00017371
Status last verified
Apr 2017
First submitted
9 Sep 2008
Last updated
15 May 2017
Data monitoring committee
No

Publications

  • Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. doi: 10.1056/NEJMoa050333.

    PubMed 16236739
  • Sassoon CS, Foster GT. Patient-ventilator asynchrony. Curr Opin Crit Care. 2001 Feb;7(1):28-33. doi: 10.1097/00075198-200102000-00005.

    PubMed 11373508
  • Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard L. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med. 2006 Oct;32(10):1515-22. doi: 10.1007/s00134-006-0301-8. Epub 2006 Aug 1.

    PubMed 16896854
  • Cooper AB, Thornley KS, Young GB, Slutsky AS, Stewart TE, Hanly PJ. Sleep in critically ill patients requiring mechanical ventilation. Chest. 2000 Mar;117(3):809-18. doi: 10.1378/chest.117.3.809.

    PubMed 10713011
  • Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003 Feb 20;348(8):683-93. doi: 10.1056/NEJMoa022450.

    PubMed 12594312
  • Hopkins RO, Weaver LK, Pope D, Orme JF, Bigler ED, Larson-LOHR V. Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999 Jul;160(1):50-6. doi: 10.1164/ajrccm.160.1.9708059.

    PubMed 10390379
  • Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

    PubMed 10793162
  • Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. doi: 10.1056/NEJM199802053380602.

    PubMed 9449727
  • Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1999 Jul 7;282(1):54-61. doi: 10.1001/jama.282.1.54.

    PubMed 10404912

Questions about this trial

What is this clinical trial studying?

A study testing APRV and Conventional MV in people with Acute Lung Injury and Acute Respiratory Distress Syndrome, run by Johns Hopkins University at 1 site in United States.

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 6 inclusion and 22 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 15 May 2017. 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 United States. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Amount of Sedatives Used (time frame: 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00750204, which also lists 9 linked publications.

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 15 May 2017.

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