Lung Injury, Acute (ALI)Phase 3CEASENCT00796419
Comparative Evaluation of Albumin and Starch Effects in Acute Lung Injury (ALI)
A Phase 3 study testing 5% human albumin and 6% hetastarch in people with Lung Injury, Acute (ALI) and Respiratory Distress Syndrome, Acute (ARDS), run by Emory University at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Injury, Acute (ALI), Respiratory Distress Syndrome, Acute (ARDS)
- What is being tested?
- 5% human albumin and 6% hetastarch
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2009to Nov 2016
- Phase
- Phase 3
- 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
- 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.
Who cannot join
- 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):
Show all 29Show fewer
- 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.
- 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 positive end-expiratory pressure (PEEP) ≤ 5, and;
- Spontaneous tidal volumes > 5 ml / kg, and;
- Spontaneous respiratory rate < 20 / minute, and;
- Capable of spontaneous ventilation on continuous positive airway pressure (CPAP)=5, pressure support (PS)=5.
- Expected survival ≤ 120 hours.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
Emory Crawford Long Hospital
Atlanta, Georgia, 30308
Emory University Hospital
Atlanta, Georgia, 30322
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Phase III Study Comparing Albumin and Hetastarch Therapy in Acute Lung Injury
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)
- Being tested
- 5% human albumin, 6% hetastarch
- Keywords
- Acute lung injury (ALI), Acute respiratory distress syndrome (ARDS), Respiratory failure
- Medical subject headings
- Lung Injury, Respiratory Distress Syndrome, Acute Lung Injury, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5% human albuminDrug
Intravenous administration of 250 milliliters (mL) 5% human albumin every 8 hours for 5 days
6% hetastarchDrug
Intravenous administration of 250mL 6% hetastarch every 8 hours for 5 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Intravenous 5% human albumin Receives: Drug: 5% human albumin |
| 2 | Experimental | Intravenous 6% hetastarch Receives: Drug: 6% hetastarch |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Day 5 (120 hours)
Secondary outcomes (2)
Change in Oxygenation (PaO2/FiO2 Ratio)
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.
Measured: Baseline, Day 1
Ventilator-free Days
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.
Measured: Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2008 (estimated)
- Study startJan 2009
- Primary completionNov 2015
- Study completionNov 2016
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.
- Other trials for Lung Injury, Acute (ALI)Studies of the same condition, open and under way.
- More trials run by Emory 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Greg S. Martin, M.D., M.Sc., Emory University
- Investigators
- Greg S Martin, MD, MSc, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00796419
- Sponsor's protocol ID
- IRB00002187
- Other IDs
- R01FD003440, 622-2000
- Acronym
- CEASE
- Status last verified
- Mar 2017
- First submitted
- 21 Nov 2008
- Last updated
- 28 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study Comparing Albumin and Hetastarch Therapy in Acute Lung Injury
- ClinicalTrials.gov ID
- NCT00796419
- Acronym / sponsor ID
- CEASE / IRB00002187
- Keywords
- Acute lung injury (ALI), Acute respiratory distress syndrome (ARDS), Respiratory failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 24 Nov 2008 (estimated)
- Results
- Posted 28 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: 5% human albuminIntravenous 5% human albumin |
| 2 | Experimental | Drug: 6% hetastarchIntravenous 6% hetastarch |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Consensus clinical definition of ALI or ARDS:
- Serum total protein concentration < 6.0 g/dL.
- Endotracheal intubation and mechanical ventilation ≥ 24 hours.
Key exclusion criteria (29 listed)
- Hemodynamic instability within the prior 24 hours: (either 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):
- Allergy to albumin, hetastarch or furosemide.
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 |
|---|---|---|
| 5% human albuminIntravenous administration of 250 milliliters (mL) 5% human albumin every 8 hours for 5 days | Drug | 1 |
| 6% hetastarchIntravenous administration of 250mL 6% hetastarch every 8 hours for 5 days | Drug | 2 |
Primary outcome
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.
2 secondary outcomes
Change in Oxygenation (PaO2/FiO2 Ratio)
Time frame: Baseline, Day 1
Ventilator-free Days
Time frame: Day 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Lung Injury, Acute (ALI)
RecruitingObservational study
Digital Early Warning System for Acute Lung Injury in Liver Surgery
Acute Lung Injury(ALI), Liver Cirrhosis
Not yet recruitingObservational study
Outer Membrane Vesicle and Ferroptosis-Related Signatures in Sepsis-Associated Acute Lung Injury Caused by Extra-Pulmonary Hypervirulent Klebsiella Pneumoniae
Sepsis, Acute Lung Injury(ALI)
RecruitingObservational study
Recovery of Physical Function After Critical Illness In Older Adults
Sepsis, Acute Lung Injury(ALI)
RecruitingObservational study
ALI & Pulmonary HA Deposition After SAH
Subarachnoid Haemorrhage (SAH)
Not yet recruiting
The Impact of Automatic Lung Recruitment Postoperative Pulmonary Complications
Acute Lung Injury
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.
Greg S Martin, MD, MSc principal investigator
Emory University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 5% human albumin and 6% hetastarch in people with Lung Injury, Acute (ALI) and Respiratory Distress Syndrome, Acute (ARDS), run by Emory University at 4 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 7 inclusion and 29 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: stopped early, as of the sponsor's last update on 28 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 28 Apr 2017). 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?
Change in Extravascular Lung Water (EVLW) (time frame: Baseline to Day 5 (120 hours)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2017.