Acute Lung InjuryPhase 2HEALNCT00624650
Hemodynamics and Extravascular Lung Water in Acute Lung Injury
A Phase 2 study testing Diuresis (furosemide) part I, Fluid Bolus (crystalloid or albumin) and Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine) in people with Acute Lung Injury, run by Oregon Health and Science University at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lung Injury
- What is being tested?
- Diuresis (furosemide) part I, Fluid Bolus (crystalloid or albumin) and Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2008to Jan 2011
- Phase
- Phase 2
- 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:
- PaO2/FiO2 less than or equal to 300.
- Bilateral infiltrates consistent with pulmonary edema on the frontal chest radiograph.
- Requirement for positive pressure ventilation through an endotracheal tube or tracheostomy.
- 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.
Who cannot join
- Age younger than 18 years old.
- Greater than 24 hours since all inclusion criteria first met.
- 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).
- Pregnancy (negative pregnancy test required for women of child-bearing potential).
- Severe chronic respiratory disease (see Appendix I.C).
- Severe Chronic Liver Disease (Child-Pugh 11 - 15, see Appendix I.E)
Show all 17Show fewer
- Weight > 160 kg.
- Burns greater than 70% total body surface area.
- Malignancy or other irreversible disease or conditions for which 6-month mortality is estimated to be greater than 50 % (see Appendix I.A).
- Known cardiac or vascular aneurysm.
- Contraindications to femoral arterial puncture - platelets < 30, bilateral femoral arterial grafts, INR > 3.0.
- Not committed to full support.
- Participation in other experimental medication trial within 30 days.
- Allergy to intravenous lasix or any components of its carrier.
- History of severe CHF - NYHA class ≥ III, previously documented EF < 30%.
- Diffuse alveolar hemorrhage.
- 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).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Kaiser Permanente Sunnyside
Clackamas, Oregon, 97015
Legacy Good Samaritan
Portland, Oregon, 97210
Oregon Health and Science University
Portland, Oregon, 97219
About this study
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
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.
Read the 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.
- Conditions
- Acute Lung Injury
- Being tested
- Diuresis (furosemide) part I, Fluid Bolus (crystalloid or albumin), Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine), Dobutamine, Concentrate all drips and nutrition
- Keywords
- Acute Lung Injury, Extravascular Lung Water, Acute Respiratory Distress Syndrome
- Medical subject headings
- Acute Lung Injury, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diuresis (furosemide) part IDrug
Goal: Overall I/O net negative 50ml/hour
Initiation:
- Continuous IV furosemide at 3mg/hour or last known protocol specified dose
- Titrate up or down by 3mg/hour increments every hour as needed to establish diuresis goal
- Do not exceed 30mg/hour
Furosemide Bolus:
- If unable to establish adequate diuresis at maximum dose may attempt furosemide bolusing as follows
- By intravenous bolus give 30, then 60, then 80, and 120 mg - one bolus dose every hour until urine output results in 1 ml/kg PBW/hr net negative fluid balance per hour
- Bolusing trials may be done at will but total furosemide dose may not exceed 800mg/24hour period
Fluid Bolus (crystalloid or albumin)Other
15 ml/kg PBW crystalloid (round to nearest 250 ml) or 25 grams albumin as rapidly as possible. Used for patients with a measured CVP<8 or measured PaOP <12mmHg in addition to concurrent urine output of <0.5 ml/kg/hr
Fluid Bolus (crystalloid or albumin)Other
10 ml/kg PBW crystalloid (round to nearest 70ml) or 25 grams albumin as rapidly as possible.
Perform thermodilution immediately before and after and 60 minutes after each bolus. If EVLW increases > 2ml/kg PBW within 60 minutes after a bolus do not give any further boluses until next regularly scheduled measurement. This therapy is available for patients with a map < 60 or who are on vasopressors that also have a measured GEDI less than goal
Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)Drug
(may use any alone or in combination)
- Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min.
- Vasopressin - 0.04 international units/hour
- Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min.
- Epinephrine - 1 mcg/min - may increase for effect not to exceed 20mcg/min.
Weaning: When MAP ≥ 60 mm/Hg on stable dose of vasopressor begin reduction of vasopressor by greater than or equal to 25% stabilizing dose at intervals ≤ 4 hours to maintain MAP ≥ 60 mm/Hg.
Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)Drug
(may use alone or in combination)
- Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min.
- Vasopressin - 0.04 international units/hour
- Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min.
- Epinephrine - 1 mcg/min - may increase for effect not to exceed 20mcg/min.
Weaning: When MAP ≥ 60 mm/Hg on stable dose of vasopressor begin reduction of vasopressor by greater than or equal to 25% stabilizing dose at intervals ≤ 4 hours to maintain MAP ≥ 60 mm/Hg.
In the experimental arm vasopressors are a treatment option in patients with a Mean Arterial Pressure of < 60
DobutamineDrug
- Begin at 5mcg/kg/min and increase by 3 mcg/kg/min increments at 15 minute intervals until C.I. ≥ 2.5 or maximum dose of 20mcg/kg/min has been reached.
- Begin weaning 4 hours after low CI is reversed. Wean by ≥ 25% of the stabilizing dose at intervals of ≤ 4 hours to maintain hemodynamic algorithm goals.
- If patient is on dobutamine as a result of an earlier cell assignment, dobutamine should be ignored for the purpose of subsequent assignment, but should be continued to be weaned per protocol.
Used in patients with a measured cardiac index < 2.5
DobutamineDrug
- Begin at 5mcg/kg/min and increase by 3 mcg/kg/min increments at 15 minute intervals until C.I. ≥ 2.5 or maximum dose of 20mcg/kg/min has been reached.
- Begin weaning 4 hours after low CI is reversed. Wean by ≥ 25% of the stabilizing dose at intervals of ≤ 4 hours to maintain hemodynamic algorithm goals.
- If patient is on dobutamine as a result of an earlier cell assignment, dobutamine should be ignored for the purpose of subsequent assignment, but should be continued to be weaned per protocol.
Concentrate all drips and nutritionOther
Concentrate all drips and nutrition in order to minimize fluid volume as much as possible. Intravenous fluid to be run at keep vein open rate.
EVLW arm: Patients with a MAP > 60 and off vasopressors for >12 hours, as well as patients with a measured cardiac index >2.5 that also have a measured GEDI > goal.
Diuresis (furosemide) part IIDrug
Withhold furosemide if:
- Significant hypokalemia (K+ <= 2.5 meq/L), or hypernatremia (Na+ >= 155 meq/L) occurs within last 12 hours may then be restarted if the prevailing condition no longer exists
- Dialysis dependence
- Oliguria (less than 0.5ml/kg/hour) with either creatinine > 3, or clinical suspicion of rapidly evolving ARF
- More than 800mg has been given in less then 24 hours
- Creatinine increases > 1.5 mg/dl in any 24 hour period
DialysisProcedure or surgery
- Need for CVVHD or intermittent hemodialysis to be determined by treating clinicians.
- CVC arm: If fluid management to be accomplished with dialysis then fluid balance goals to be determined per clinicians.
- EVLW arm: Fluid balance as per algorithm
- When using intermittent HD it is recommended that no more than 2 liters net negative fluid is removed per dialysis session. Total fluid removal per run to be estimated by the clinicians to attain CVP or GEDI goals per algorithm.
| Study group | Role | What they receive |
|---|---|---|
| Modified FACTT (control) | Active comparator | The investigators control arm consists of a simplified algorithm for conservative management of fluids in patients with ALI, as to be published by the ARDSnet group, based on the protocol used in the FACTT trial. The protocol calls for strict adherence to ARDSnet ventilation, our weaning protocol and use of only select vasoactive, beta-adrenergic drugs as it is felt that variation in these treatments could seriously confound our results. Albuterol administration will not be permitted in the either arm except for life threatening bronchospasm not responsive to ipratropium. Ipratropium may be administered at the treating physician's discretion for bronchospasm. PiCCO's will be placed in each control patient and data recorded twice daily. The treating physician's will be blinded to this data. Receives: Drug: Diuresis (furosemide) part I; Other: Fluid Bolus (crystalloid or albumin); Drug: Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine); Drug: Dobutamine; Drug: Diuresis (furosemide) part II; Procedure: Dialysis |
| EVLW | Experimental | When EVLW exceeds 9 ml/kg PBW the algorithmic treatment is begun and continued until EVLW ≤9 ml/kg PBW or extubation whichever comes first as tolerated (see figure 6). Furosemide and volume contraction are initiated when sufficient volumetric preload (GEDI) is available to enact volume contraction as a means to decrease measured EVLW without causing concomitant hypoperfusion. Fluid administration is also guided by changes in EVLW. An increase in EVLW > 2ml/kg PBW as a result of fluid administration curtails any further fluid administration until the next scheduled measurement.
Our ultimate treatment goal is to maximally lower EVLW towards the normal range - thus improving lung mechanics and gas exchange - without causing concomitant hemodynamic compromise and end-organ injury. By doing so we feel this algorithmic, goal directed, therapeutic approach should improve outcome. Receives: Drug: Diuresis (furosemide) part I; Other: Fluid Bolus (crystalloid or albumin); Drug: Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine); Drug: Dobutamine; Other: Concentrate all drips and nutrition; Drug: Diuresis (furosemide) part II; Procedure: Dialysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Efficacy Variable Will be the Total Reduction in Measured Lung Water
Measured: The first seven days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (79)Papers the sponsor has linked to this study.
- Other trials for Acute Lung InjuryStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Pulsion Medical Systems, Oregon Clinical and Translational Research Institute
- Responsible party
- Sponsor
- Investigators
- Charles Phillips, M.D., Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00624650
- Sponsor's protocol ID
- IRB00003491
- Other IDs
- IRB #e2978
- Acronym
- HEAL
- Status last verified
- Aug 2019
- First submitted
- 19 Feb 2008
- Last updated
- 10 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1334-49. doi: 10.1056/NEJM200005043421806. No abstract available.
PubMed 10793167Matthay MA. Alveolar fluid clearance in patients with ARDS: does it make a difference? Chest. 2002 Dec;122(6 Suppl):340S-343S. doi: 10.1378/chest.122.6_suppl.340s.
PubMed 12475812Mitchell JP, Schuller D, Calandrino FS, Schuster DP. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis. 1992 May;145(5):990-8. doi: 10.1164/ajrccm/145.5.990.
PubMed 1586077Eisenberg PR, Hansbrough JR, Anderson D, Schuster DP. A prospective study of lung water measurements during patient management in an intensive care unit. Am Rev Respir Dis. 1987 Sep;136(3):662-8. doi: 10.1164/ajrccm/136.3.662.
PubMed 3307570National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21.
PubMed 16714767Bendjelid K, Romand JA. Fluid responsiveness in mechanically ventilated patients: a review of indices used in intensive care. Intensive Care Med. 2003 Mar;29(3):352-60. doi: 10.1007/s00134-002-1615-9. Epub 2003 Jan 21.
PubMed 12536268Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002 Jun;121(6):2000-8. doi: 10.1378/chest.121.6.2000.
PubMed 12065368Goedje O, Seebauer T, Peyerl M, Pfeiffer UJ, Reichart B. Hemodynamic monitoring by double-indicator dilution technique in patients after orthotopic heart transplantation. Chest. 2000 Sep;118(3):775-81. doi: 10.1378/chest.118.3.775.
PubMed 10988202Bernard GR. Acute respiratory distress syndrome: a historical perspective. Am J Respir Crit Care Med. 2005 Oct 1;172(7):798-806. doi: 10.1164/rccm.200504-663OE. Epub 2005 Jul 14.
PubMed 16020801Acute 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 10793162Rubenfeld 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 16236739Matthay MA, Zimmerman GA. Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol. 2005 Oct;33(4):319-27. doi: 10.1165/rcmb.F305. No abstract available.
PubMed 16172252Groeneveld AB, Polderman KH. Acute lung injury, overhydration or both? Crit Care. 2005 Apr;9(2):136-7. doi: 10.1186/cc3039. Epub 2005 Jan 17.
PubMed 15774062Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 May;163(6):1376-83. doi: 10.1164/ajrccm.163.6.2004035.
PubMed 11371404Sakka SG, Klein M, Reinhart K, Meier-Hellmann A. Prognostic value of extravascular lung water in critically ill patients. Chest. 2002 Dec;122(6):2080-6. doi: 10.1378/chest.122.6.2080.
PubMed 12475851
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00624650
- Acronym / sponsor ID
- HEAL / IRB00003491
- Conditions
- Acute Lung Injury
- Keywords
- Acute Lung Injury, Extravascular Lung Water, Acute Respiratory Distress Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Pulsion Medical Systems, Oregon Clinical and Translational Research Institute
- Study start
- Feb 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 27 Feb 2008 (estimated)
- Results
- Posted 10 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Modified FACTT (control) | Active comparator | Drug: Diuresis (furosemide) part I, Other: Fluid Bolus (crystalloid or albumin), Drug: Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine), Drug: Dobutamine, Drug: Diuresis (furosemide) part II, Procedure: DialysisThe investigators control arm consists of a simplified algorithm for conservative management of fluids in patients with ALI, as to be published by the ARDSnet group, based on the protocol used in the FACTT trial. The protocol calls for strict adherence to ARDSnet ventilation, our weaning protocol and use of only select vasoactive, beta-adrenergic drugs as it is felt that variation in these treatments could seriously confound our results. Albuterol administration will not be permitted in the either arm except for life threatening bronchospasm not responsive to ipratropium. Ipratropium may be administered at the treating physician's discretion for bronchospasm. PiCCO's will be placed in each control patient and data recorded twice daily. The treating physician's will be blinded to this data. |
| EVLW | Experimental | Drug: Diuresis (furosemide) part I, Other: Fluid Bolus (crystalloid or albumin), Drug: Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine), Drug: Dobutamine, Other: Concentrate all drips and nutrition, Drug: Diuresis (furosemide) part II, Procedure: DialysisWhen EVLW exceeds 9 ml/kg PBW the algorithmic treatment is begun and continued until EVLW ≤9 ml/kg PBW or extubation whichever comes first as tolerated (see figure 6). Furosemide and volume contraction are initiated when sufficient volumetric preload (GEDI) is available to enact volume contraction as a means to decrease measured EVLW without causing concomitant hypoperfusion. Fluid administration is also guided by changes in EVLW. An increase in EVLW > 2ml/kg PBW as a result of fluid administration curtails any further fluid administration until the next scheduled measurement. Our ultimate treatment goal is to maximally lower EVLW towards the normal range - thus improving lung mechanics and gas exchange - without causing concomitant hemodynamic compromise and end-organ injury. By doing so we feel this algorithmic, goal directed, therapeutic approach should improve outcome. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- PaO2/FiO2 less than or equal to 300.
- Bilateral infiltrates consistent with pulmonary edema on the frontal chest radiograph.
- Requirement for positive pressure ventilation through an endotracheal tube or tracheostomy.
- 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.
Key exclusion criteria (17 listed)
- Age younger than 18 years old.
- Greater than 24 hours since all inclusion criteria first met.
- 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).
- Pregnancy (negative pregnancy test required for women of child-bearing potential).
- Severe chronic respiratory disease (see Appendix I.C).
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 |
|---|---|---|
| Diuresis (furosemide) part IGoal: Overall I/O net negative 50ml/hour Initiation: 1. Continuous IV furosemide at 3mg/hour or last known protocol specified dose 2. Titrate up or down by 3mg/hour increments every hour as needed to establish diuresis goal 3. Do not exceed 30mg/hour Furosemide Bolus: 1. If unable to establish adequate diuresis at maximum dose may attempt furosemide bolusing as follows 2. By intravenous bolus give 30, then 60, then 80, and 120 mg - one bolus dose every hour until urine output results in 1 ml/kg PBW/hr net negative fluid balance per hour 3. Bolusing trials may be done at will but total furosemide dose may not exceed 800mg/24hour period | Drug | EVLW, Modified FACTT (control) |
| Fluid Bolus (crystalloid or albumin)15 ml/kg PBW crystalloid (round to nearest 250 ml) or 25 grams albumin as rapidly as possible. Used for patients with a measured CVP<8 or measured PaOP <12mmHg in addition to concurrent urine output of <0.5 ml/kg/hr | Other | Modified FACTT (control) |
| Fluid Bolus (crystalloid or albumin)10 ml/kg PBW crystalloid (round to nearest 70ml) or 25 grams albumin as rapidly as possible. Perform thermodilution immediately before and after and 60 minutes after each bolus. If EVLW increases > 2ml/kg PBW within 60 minutes after a bolus do not give any further boluses until next regularly scheduled measurement. This therapy is available for patients with a map < 60 or who are on vasopressors that also have a measured GEDI less than goal | Other | EVLW |
| Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)(may use any alone or in combination) 1. Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min. 2. Vasopressin - 0.04 international units/hour 3. Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min. 4. Epinephrine - 1 mcg/min - may increase for effect not to exceed 20mcg/min. Weaning: When MAP ≥ 60 mm/Hg on stable dose of vasopressor begin reduction of vasopressor by greater than or equal to 25% stabilizing dose at intervals ≤ 4 hours to maintain MAP ≥ 60 mm/Hg. | Drug | Modified FACTT (control) |
| Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine)(may use alone or in combination) 1. Norepinephrine - 0.05mcg/kg/min - increase for effect not to exceed (NTE) 1mcg/kg/min. 2. Vasopressin - 0.04 international units/hour 3. Phenylephrine - 7mcg/min - may increase to for effect not to exceed 500mcg/min. 4. Epinephrine - 1 mcg/min - may increase for effect not to exceed 20mcg/min. Weaning: When MAP ≥ 60 mm/Hg on stable dose of vasopressor begin reduction of vasopressor by greater than or equal to 25% stabilizing dose at intervals ≤ 4 hours to maintain MAP ≥ 60 mm/Hg. In the experimental arm vasopressors are a treatment option in patients with a Mean Arterial Pressure of < 60 | Drug | EVLW |
| Dobutamine1. Begin at 5mcg/kg/min and increase by 3 mcg/kg/min increments at 15 minute intervals until C.I. ≥ 2.5 or maximum dose of 20mcg/kg/min has been reached. 2. Begin weaning 4 hours after low CI is reversed. Wean by ≥ 25% of the stabilizing dose at intervals of ≤ 4 hours to maintain hemodynamic algorithm goals. 3. If patient is on dobutamine as a result of an earlier cell assignment, dobutamine should be ignored for the purpose of subsequent assignment, but should be continued to be weaned per protocol. Used in patients with a measured cardiac index < 2.5 | Drug | EVLW |
| Dobutamine1. Begin at 5mcg/kg/min and increase by 3 mcg/kg/min increments at 15 minute intervals until C.I. ≥ 2.5 or maximum dose of 20mcg/kg/min has been reached. 2. Begin weaning 4 hours after low CI is reversed. Wean by ≥ 25% of the stabilizing dose at intervals of ≤ 4 hours to maintain hemodynamic algorithm goals. 3. If patient is on dobutamine as a result of an earlier cell assignment, dobutamine should be ignored for the purpose of subsequent assignment, but should be continued to be weaned per protocol. | Drug | Modified FACTT (control) |
| Concentrate all drips and nutritionConcentrate all drips and nutrition in order to minimize fluid volume as much as possible. Intravenous fluid to be run at keep vein open rate. EVLW arm: Patients with a MAP > 60 and off vasopressors for >12 hours, as well as patients with a measured cardiac index >2.5 that also have a measured GEDI > goal. | Other | EVLW |
| Diuresis (furosemide) part IIWithhold furosemide if: 1. Significant hypokalemia (K+ <= 2.5 meq/L), or hypernatremia (Na+ >= 155 meq/L) occurs within last 12 hours may then be restarted if the prevailing condition no longer exists 2. Dialysis dependence 3. Oliguria (less than 0.5ml/kg/hour) with either creatinine > 3, or clinical suspicion of rapidly evolving ARF 4. More than 800mg has been given in less then 24 hours 5. Creatinine increases > 1.5 mg/dl in any 24 hour period | Drug | EVLW, Modified FACTT (control) |
| Dialysis1. Need for CVVHD or intermittent hemodialysis to be determined by treating clinicians. 2. CVC arm: If fluid management to be accomplished with dialysis then fluid balance goals to be determined per clinicians. 3. EVLW arm: Fluid balance as per algorithm 4. When using intermittent HD it is recommended that no more than 2 liters net negative fluid is removed per dialysis session. Total fluid removal per run to be estimated by the clinicians to attain CVP or GEDI goals per algorithm. | Procedure or surgery | EVLW, Modified FACTT (control) |
Primary outcome
The Primary Efficacy Variable Will be the Total Reduction in Measured Lung Water
Time frame: The first seven days of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10793167Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1334-49. doi: 10.1056/NEJM200005043421806. No abstract available.
- Background: PubMed 12475812Matthay MA. Alveolar fluid clearance in patients with ARDS: does it make a difference? Chest. 2002 Dec;122(6 Suppl):340S-343S. doi: 10.1378/chest.122.6_suppl.340s.
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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.
Charles Phillips, M.D. principal investigator
Oregon Health and Science University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diuresis (furosemide) part I, Fluid Bolus (crystalloid or albumin) and Vasopressors (Norepinephrine, Vasopressin, Phenylephrine, Epinephrine) in people with Acute Lung Injury, run by Oregon Health and Science University at 3 sites 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 5 inclusion and 17 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: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2019). 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?
The Primary Efficacy Variable Will be the Total Reduction in Measured Lung Water (time frame: The first seven days of treatment). 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 NCT00624650, which also lists 79 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 10 Sep 2019.