Comparative Evaluation of Albumin and Starch Effects in Acute Lung Injury (ALI) (CEASE)
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are similar conditions in which the lungs are critically injured by another inflammatory process in the body. Together they affect more than 150,000 people per year in the United States, with mortality approaching 50% and a financial burden estimated to exceed $5 billion. Fluid overload, weight gain, and reduced oncotic pressure (low blood proteins) are associated with prolonged need for mechanical ventilation and mortality in patients with ALI/ARDS. Historical studies have provided conflicting evidence for benefits with colloid or diuretic therapy in ALI/ARDS, but recent clinical trials have demonstrated significant improvements in blood oxygen levels. The mechanisms of these benefits are not yet certain, but appear to relate to albumin's (a protein medicine) specific ability to influence injury and inflammation in the lungs, thus improving the ability for the lung to repair and exchange oxygen.
The purpose of this project is to determine the effects of therapies that affect blood proteins on their ability to change the way the lungs and cardiovascular system (heart and blood vessels) function. Special measurements will be taken to understand how these protein medicines change the ability of the lung and whole body to recover from widespread injury, with additional measures of specific heart and lung function. This clinical trial randomizes ALI/ARDS patients with low blood protein levels to receive albumin (a natural blood protein that is known to influence inflammation) or hetastarch (a synthetic blood protein) with diuretic therapy targeted to improve respiratory function. Therapeutic effects on respiratory function and blood oxygen levels, extravascular lung water, oncotic pressure, lung fluid removal, and heart function will be characterized. This trial will advance our understanding of treatment of ALI/ARDS and the factors that affect fluid balance in the lungs of these patients.
Funding Source - FDA Office of Orphan Products Development (OOPD)
|Lung Injury, Acute (ALI) Respiratory Distress Syndrome, Acute (ARDS)||Drug: 5% human albumin Drug: 6% hetastarch||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase III Study Comparing Albumin and Hetastarch Therapy in Acute Lung Injury|
- Change in Extravascular Lung Water (EVLW) [ Time Frame: Baseline to Day 5 (120 hours) ]Quantity of extravascular lung water (EVLW) measured by transpulmonary thermodilution. Higher measurements of EVLW per kilogram of body weight indicate increased lung injury. Normal values for EVLW are thought to be less than 10 mL/kg.
- Change in Oxygenation (PaO2/FiO2 Ratio) [ Time Frame: Baseline, Day 1 ]Change in arterial oxygenation measured by arterial blood gas analysis. The partial pressure of O2 in arterial blood to fraction of inspired oxygen ratio (PaO2/FiO2) is a ratio of partial pressure arterial oxygen to fractional inspired inspired oxygen. This ratio is used as an indicator of hypoxemia (low blood oxygen). A PaO2/FiO2 ratio of 200-300 indicates mild ARDS, 100-200 indicates moderate ARDS, and less than 100 indicates severe ARDS.
- Ventilator-free Days [ Time Frame: Day 30 ]The 'ventilator free survival days' in a 30-day period is a previously validated method of comparing groups with respect to mechanical ventilator requirements while adjusting for mortality. This variable represents the number of days in the 30-day period following baseline that the patient is alive and not requiring mechanical ventilation.
|Study Start Date:||January 2009|
|Study Completion Date:||November 2016|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Intravenous 5% human albumin
Drug: 5% human albumin
Intravenous administration of 250 milliliters (mL) 5% human albumin every 8 hours for 5 days
Intravenous 6% hetastarch
Drug: 6% hetastarch
Intravenous administration of 250mL 6% hetastarch every 8 hours for 5 days
Please refer to this study by its ClinicalTrials.gov identifier: NCT00796419
|United States, Georgia|
|Grady Memorial Hospital|
|Atlanta, Georgia, United States, 30303|
|Emory Crawford Long Hospital|
|Atlanta, Georgia, United States, 30308|
|Emory University Hospital|
|Atlanta, Georgia, United States, 30322|
|United States, North Carolina|
|Wake Forest Baptist Medical Center|
|Winston-Salem, North Carolina, United States, 27157|
|Principal Investigator:||Greg S Martin, MD, MSc||Emory University|