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Hemodynamics and Extravascular Lung Water in Acute Lung Injury

Information source: Oregon Health and Science University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Lung Injury

Intervention: Diuresis (furosemide) part I (Drug); Fluid Bolus (crystalloid or albumin) (Other); Fluid Bolus (crystalloid or albumin) (Other); Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine) (Drug); Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine) (Drug); Dobutamine (Drug); Dobutamine (Drug); Concentrate all drips and nutrition (Other); Diuresis (furosemide) part II (Drug); Dialysis (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: Oregon Health and Science University

Official(s) and/or principal investigator(s):
Charles Phillips, M.D., Principal Investigator, Affiliation: Oregon Health and Science University


The purpose of this study is to test a treatment that tries to reduce the amount of fluid in the lungs of subjects with acute lung injury to see if this is helpful.

Clinical Details

Official title: Hemodynamics and Extravascular Lung Water in Acute Lung Injury: A Prospective Randomized Controlled Multicentered Trial of Goal Directed Treatment of EVLW Versus Standard Management for the Treatment of Acute Lung Injury

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Primary outcome: The primary efficacy variable will be the total reduction in measured lung water

Secondary outcome:

The number of ventilator-free days (VFDs

The physiologic severity of clinical lung injury as measured by the 4-point acute lung injury scoring system.

Number of ICU-free days

Number of Organ Failure Free Days

Percentage of patients alive at day 28 in patients with ALI

Percentage of patients discharged alive from hospital within 60 days

Mortality and VFDs in patients with pre- randomization PaO2/FiO2 less than or equal to 200

Mortality prior to hospital discharge to day 60 in patients who receive norepinephrine, dobutamine, or vasopressin at any point during the treatment period

number of VFDs to day 28 in patients who receive the following intravenous vasoactive agonists (norepinephrine, dobutamine, and vasopressin) at any point during the treatment period

Mortality prior to hospital discharge to day 60 in patients with shock (defined in 2.3.6 in the HEAL protocol) at the time of randomization

number of VFDs to day 28 in patients with shock (defined in 2.3.6 in the HEAL protocol) at the time of randomization

Mortality prior to hospital discharge to day 60 in patients with severe sepsis (defined in 2.3.8 in the HEAL protocol) at the time of randomization.

number of ventilator-free days to day 28 in patients with severe sepsis (defined in 2.3.8) at the time of randomization.

Changes in quasistatic total respiratory system compliance

Need for vasoactive medication - dose, duration and total amounts of all vasoactive medications.

Changes in the plasma levels of interleukin-1b, 6 and 8, and TNF-α.

Changes in the airspace (bronchoalveolar lavage: BAL) levels of interleukin-1b, 6 and 8, and TNF-α. Changes in BAL cell count and differential.

Detailed description: The objective of this study is to conduct a randomized, controlled trial of a goal directed therapy designed to improve outcome in patients with acute lung injury (ALI). The

investigators are comparing two algorithmic approaches in managing patients with ALI - one,

the control arm, attempts to reduce the amount of fluid in the lung in patients with ALI by diuresis based on central venous pressure and urine output, the other the treatment arm attempting to reduce lung water by directing therapy to measured lung water and using more sensitive indicators of preload status than CVP. The protocol uses measured extravascular lung water (EVLW) to direct diuresis and appropriate fluid restriction in a goal directed fashion in order to lower EVLW towards the normal range.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: Acute onset of: 1. PaO2/FiO2 less than or equal to 300. 2. Bilateral infiltrates consistent with pulmonary edema on the frontal chest radiograph. 3. Requirement for positive pressure ventilation through an endotracheal tube or tracheostomy. 4. No clinical evidence of left atrial hypertension that would explain the pulmonary infiltrates. If measured, pulmonary arterial wedge pressure less than or equal to 18 mmHg. Exclusion Criteria: 1. Age younger than 18 years old. 2. Greater than 24 hours since all inclusion criteria first met. 3. Neuromuscular disease that impairs ability to ventilate without assistance, such as C5 or higher spinal cord injury, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenia gravis, or kyphoscoliosis (see Appendix I. A). 4. Pregnancy (negative pregnancy test required for women of child-bearing potential). 5. Severe chronic respiratory disease (see Appendix I. C).

6. Severe Chronic Liver Disease (Child-Pugh 11 - 15, see Appendix I. E)

7. Weight > 160 kg. 8. Burns greater than 70% total body surface area. 9. Malignancy or other irreversible disease or conditions for which 6-month mortality is estimated to be greater than 50 % (see Appendix I. A). 10. Known cardiac or vascular aneurysm.

11. Contraindications to femoral arterial puncture - platelets < 30, bilateral femoral

arterial grafts, INR > 3. 0. 12. Not committed to full support. 13. Participation in other experimental medication trial within 30 days. 14. Allergy to intravenous lasix or any components of its carrier.

15. History of severe CHF - NYHA class ≥ III, previously documented EF < 30%.

16. Diffuse alveolar hemorrhage. 17. Presence of reactive airway disease (active will be defined based on recent frequency and amounts of MDI's use and steroids to control the disease).

Locations and Contacts

Kaiser Permanente Sunnyside, Clackamas, Oregon 97015, United States

Legacy Good Samaritan, Portland, Oregon 97210, United States

Oregon Health and Science University, Portland, Oregon 97219, United States

Additional Information

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Starting date: February 2008
Last updated: May 27, 2011

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