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

NCT00796419 | Terminated Phase 3 Results DMC

• 3 other identifiers: IRB00002187R01FD003440622-2000
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

Brief Summary

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)

Conditions

Lung Injury, Acute (ALI); Respiratory Distress Syndrome, Acute (ARDS)

Keywords

Acute lung injury (ALI); Acute respiratory distress syndrome (ARDS); Respiratory failure

Outcome Measures

Primary Outcomes (1)

• Change in Extravascular Lung Water (EVLW)

  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.

  Baseline to Day 5 (120 hours)

Secondary Outcomes (2)

• Change in Oxygenation (PaO2/FiO2 Ratio)

  Baseline, Day 1

• Ventilator-free Days

  Day 30

Study Arms (2)

1

EXPERIMENTAL

Intravenous 5% human albumin

Drug: 5% human albumin

2

EXPERIMENTAL

Intravenous 6% hetastarch

Drug: 6% hetastarch

Interventions

5% human albumin DRUG

Intravenous administration of 250 milliliters (mL) 5% human albumin every 8 hours for 5 days

1

6% hetastarch DRUG

Intravenous administration of 250mL 6% hetastarch every 8 hours for 5 days

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consensus clinical definition of ALI or ARDS:
• Partial pressure of oxygen in arterial blood to the fraction of inspired oxygen (PaO2 / FiO2) ratio ≤ 200 (ARDS) or ≤ 300 (ALI), and;
• Bilateral infiltrates on chest x-ray, and;
• No clinical evidence of congestive heart failure, and;
• Pulmonary artery occlusion pressure (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.

You may not qualify if:

• 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 Glasgow Coma Scal (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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (4)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory Crawford Long Hospital

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Lung Injury; Respiratory Distress Syndrome; Acute Lung Injury; Respiratory Insufficiency

Interventions

Serum Albumin, Human; Hydroxyethyl Starch Derivatives

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Thoracic Injuries; Wounds and Injuries; Respiration Disorders

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins; Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Results Point of Contact

• Title: Greg Martin, MD, MSc
• Organization: Emory University

greg.martin@emory.edu

404-616-0148

Study Officials

• Greg S Martin, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 21, 2008
• First Posted: November 24, 2008
• Study Start: January 1, 2009
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: April 28, 2017
• Results First Posted: April 28, 2017

Record last verified: 2017-03

Locations

US (4)