Comparative Evaluation of Albumin and Starch Effects in Acute Lung Injury (ALI) (CEASE)

This study has suspended participant recruitment.
(Pending DSMB review)
Sponsor:
Information provided by (Responsible Party):
Greg S. Martin, M.D., M.Sc., Emory University
ClinicalTrials.gov Identifier:
NCT00796419
First received: November 21, 2008
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Lung Injury, Acute (ALI)
Respiratory Distress Syndrome, Acute (ARDS)
Drug: 5% human albumin
Drug: 6% hetastarch
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III Study Comparing Albumin and Hetastarch Therapy in Acute Lung Injury

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Change in extravascular lung water (EVLW) [ Time Frame: Day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in oxygenation (PaO2/FiO2 ratio) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Duration of mechanical ventilation (ventilator-free days) [ Time Frame: Day 30 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Intravenous 5% human albumin
Drug: 5% human albumin
Intravenous administration of 250mL 5% human albumin every 8 hours for 5 days
Experimental: 2
Intravenous 6% hetastarch
Drug: 6% hetastarch
Intravenous administration of 250mL 6% hetastarch every 8 hours for 5 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00796419

Locations
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
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Greg S Martin, MD, MSc Emory University
  More Information

No publications provided

Responsible Party: Greg S. Martin, M.D., M.Sc., Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT00796419     History of Changes
Other Study ID Numbers: 622-2000, R01 FD-003440
Study First Received: November 21, 2008
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Acute lung injury (ALI)
Acute respiratory distress syndrome (ARDS)
Respiratory failure

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Wounds and Injuries
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
Hetastarch
Plasma Substitutes
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014