Lung Injury, Acute (ALI) Clinical Trial
— CEASEOfficial title:
Phase III Study Comparing Albumin and Hetastarch Therapy in Acute Lung Injury
| Verified date | August 2016 |
| Source | Emory University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
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 OOPD
| Status | Terminated |
| Enrollment | 31 |
| Est. completion date | November 2016 |
| Est. primary completion date | November 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Consensus clinical definition of ALI or ARDS: - PaO2 / FiO2 ratio = 200 (ARDS) or = 300 (ALI), and; - Bilateral infiltrates on chest x-ray, and; - No clinical evidence of congestive heart failure, and; - PAOP = 18 mm Hg, if a pulmonary arterial catheter is present - Serum total protein concentration < 6.0 g/dL. - Endotracheal intubation and mechanical ventilation = 24 hours. Exclusion Criteria: - Hemodynamic instability within the prior 24 hours: (either of the following) - Ongoing fluid resuscitation defined as > 2 liters of crystalloid boluses or > 4 units of blood products transfused in the prior 24-hour period. - Vasopressor support exceeding any of the following: - Dopamine or dobutamine > 5 mcg/kg/min, or in combination at any dose; or - Any other vasoactive agent (i.e. epinephrine, norepinephrine, phenylephrine) - Significant renal disease (either of the following at the time of screening): - End-stage renal disease, or - Renal insufficiency with serum creatinine = 3.0 mg/dL or urine output < 500cc/24 hrs - Allergy to albumin, hetastarch or furosemide. - Increased risk for bleeding: - Within 72 hours of any surgical procedure requiring use of the operating room, or - Any current or previously diagnosed bleeding disorder, or - History of any intracranial abnormality (including, but not limited to, intracranial arteriovenous malformations, subdural/subarachnoid/intracerebral hemorrhage, intracranial mass lesions) or traumatic brain injury with GCS < 9 in the prior 14 days, or - Prothrombin time international normalized ratio (INR) > 2.0, partial thromboplastin time (PTT) > 1.5 times control, platelet count < 50,000/cc3 - Risk for worsening pulmonary edema due to systolic heart failure. - Technical pulse contour analysis limitations: - Absence of central venous catheter, clinical arterial vascular disease, severe hypothermia (core temperature < 94°F), weight < 40 kg or > 250 kg, clinically significant bleeding diathesis. - Failure of the patient or nearest relative to provide informed consent. - Refusal of the patient's attending physician to provide consent to participate. - Age < 18 years. - Pregnancy. - Inability to quantify urine output (e.g. absence of bladder or bladder catheter). - Significant hypokalemia (K+ < 3.5 meq/L), hypernatremia (Na+ > 155 meq/L) or hypomagnesemia (Mg < 1.0 meq/L) - Patient meets criteria for weaning mechanical ventilation: - Required FiO2 = 0.40 and PEEP = 5, and; - Spontaneous tidal volumes > 5 ml / kg, and; - Spontaneous respiratory rate < 20 / minute, and; - Capable of spontaneous ventilation on CPAP=5, PS=5. - Expected survival = 120 hours. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Emory Crawford Long Hospital | Atlanta | Georgia |
| United States | Emory University Hospital | Atlanta | Georgia |
| United States | Grady Memorial Hospital | Atlanta | Georgia |
| United States | Wake Forest Baptist Medical Center | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Emory University |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in extravascular lung water (EVLW) | Day 5 | No | |
| Secondary | Change in oxygenation (PaO2/FiO2 ratio) | Day 1 | No | |
| Secondary | Duration of mechanical ventilation (ventilator-free days) | Day 30 | No |