Respiratory Distress Syndrome, AdultPhase 2/3ALTANCT00434993
Drug Study of Albuterol to Treat Acute Lung Injury
A Phase 2/3 study testing Albuterol Sulfate and Mini-Bronchoalveolar Lavage (BAL) in people with Respiratory Distress Syndrome, Adult, run by National Heart, Lung, and Blood Institute (NHLBI) at 40 sites in United States.
Trial summary
Acute Respiratory Distress Syndrome (ARDS) and a lesser condition that occurs prior to ARDS, Acute Lung Injury (ALI), are medical conditions that occur when there is severe inflammation and increased fluids (edema) in both lungs, making it hard for the lungs to function properly. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Respiratory Distress Syndrome, Adult
- What is being tested?
- Albuterol Sulfate and Mini-Bronchoalveolar Lavage (BAL)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 282 participants
- Where
- 40 sitesUnited States
- Study dates
- Aug 2007to Nov 2008
- Phase
- Phase 2/3
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Must meet the following three criteria within a 24-hour period:
- Acute onset of PaO2/FiO2 less than or equal to 300 (adjustments made for altitude where appropriate)
- Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
- Requirement for positive pressure ventilation via endotracheal tube
- No clinical evidence of left-sided cardiac failure to account for bilateral pulmonary infiltrates
Who cannot join
- Greater than 48 hours since all inclusion criteria are met
- Neuromuscular disease that impairs ability to ventilate without assistance, (e.g., cervical spinal cord injury at level C5 or higher spinal cord injury amyotrophic lateral sclerosis, Guillain-Barré syndrome or myasthenia gravis)
- Pregnant or breast-feeding
- Severe chronic respiratory disease (i.e., chronic hypercapnia [PaCO2 greater than 45 mmHg], chronic hypoxemia [PaO2 less than 55 mmHg on FiO2 = 0.21], hospitalization within the last 6 months for respiratory failure [PaCO2 greater than 50 mm Hg and/or PaO2 less than 55 mmHg on 0.21 FiO2], secondary polycythemia, severe pulmonary hypertension [mean PAP (pulmonary artery pressure) greater than 40 mmHg], or ventilator dependency)
- Burns over greater than 40% of total body surface area
- Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
Show all 22Show fewer
- Allogeneic bone marrow transplant within the 5 years prior to study entry
- Participant, surrogate, or physician is not committed to full support (Exception: a participant will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
- Severe chronic liver disease (Child-Pugh score of 11-15)
- Diffuse alveolar hemorrhage from vasculitis
- Morbid obesity (greater than 1kg/cm body weight.)
- Unwillingness or inability to utilize the ARDS network 6 ml / kg Predicted Body Weight (PBW) ventilation protocol
- Moribund participant and is not expected to survive 24 hours
- No intent to obtain central venous access for monitoring intravascular pressures
- Contraindication to aerosolized albuterol (see Appendix A.8 of the protocol for more information)
- Daily use (prior to study hospitalization) of inhaled beta agonist, corticosteroid, or oral leukotriene modifier
- Unwillingness of primary physician to discontinue inpatient beta agonist use
- Acute myocardial infarction or acute coronary syndrome within 30 days of study entry
- Severe congestive heart failure (see Appendix A5 of the protocol for more information)
- Participation in other experimental medication trial within 30 days of study entry with the exception of the ARDSNet pharmaconutrient nutrition trial (OMEGA)
- Heart rate greater than 85% of maximal predicted heart rate (MHR85) as calculated by MHR85 = 85% x (220-age)
- Currently receiving high frequency ventilation
Trial locations and contacts
40 sites in 1 country.
40 sites in 1 country
United States40 sites
Baltimore VA Medical Center
Baltimore, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland
Johns Hopkins Hospital
Baltimore, Maryland
University of Maryland Shock Trauma Center
Baltimore, Maryland
Baton Rouge General Hospital-Blue Bonnet
Baton Rouge, Louisiana
Baton Rouge General Hospital-Midcity
Baton Rouge, Louisiana
Earl K. Long Medical Center
Baton Rouge, Louisiana
Our Lady of the Lake Regional Medical Center
Baton Rouge, Louisiana
University of North Carolina
Chapel Hill, North Carolina
University of Virginia Medical Center
Charlottesville, Virginia
Cleveland Clinic Foundation
Cleveland, Ohio
MetroHealth Medical Center
Cleveland, Ohio
University Hospitals of Cleveland
Cleveland, Ohio
Centura St. Anthony Central Hospital
Denver, Colorado
Denver Health Medical Center
Denver, Colorado
Rose Medical Center
Denver, Colorado
University of Colorado Health Sciences Center
Denver, Colorado
Duke University Medical Center
Durham, North Carolina
Durham Regional Medical Center
Durham, North Carolina
University of San Francisco-Fresno Medical Center
Fresno, California
Moses Cone Health System
Greensboro, North Carolina
Wesley Long Community Hospital
Greensboro, North Carolina
Baylor College of Medicine
Houston, Texas
Vanderbilt University Medical Center
Nashville, Tennessee
Medical Center of Louisiana
New Orleans, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana
McKay-Dee Hospital
Ogden, Utah
Utah Valley Regional Medical Center
Provo, Utah
Rochester Methodist Hospital
Rochester, Minnesota
St. Mary's Hospital, Mayo Clinic
Rochester, Minnesota
University of California, Davis Medical Center
Sacramento, California
LDS Hospital
Salt Lake City, Utah
UCSF-Moffitt Hospital
San Francisco, California
UCSF-San Francisco General Hospital
San Francisco, California
Harborview Medical Center
Seattle, Washington
University of Washington
Seattle, Washington
Baystate Medical Center
Springfield, Massachusetts
Washington Hospital Center
Washington D.C., District of Columbia
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina
About this study
Official title: Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo in Acute Lung Injury
Acute Respiratory Distress Syndrome (ARDS) and a lesser condition that occurs prior to ARDS, Acute Lung Injury (ALI), are medical conditions that occur when there is severe inflammation and increased fluids (edema) in both lungs, making it hard for the lungs to function properly. Patients with these conditions require treatment that includes the use of a breathing machine (ventilator). The purpose of this study is to find out whether giving albuterol (a drug commonly used in asthmatics) or not giving albuterol to patients with ALI or ARDS makes a difference in how long it takes for a patient to be able to breath without the ventilator.
Read the detailed description
Aerosolized beta-2 agonist therapy is anticipated to diminish the formation of lung edema, enhance clearance of lung edema and decrease pulmonary inflammation in patients with acute lung injury. Because beta-2 agonists have been shown to reduce permeability induced lung injury, it is anticipated that the severity of lung injury will be reduced by aerosolized beta-2 agonist therapy. The therapy may work by enhancing resolution of pulmonary edema by upregulating alveolar epithelial fluid transport mechanisms that will in turn enhance the clearance of alveolar edema. A reduction in the severity of lung injury and the quantity of alveolar edema should result in earlier extubation and more ventilator free days, improved pulmonary oxygen uptake, and improved lung compliance.
Study design: phase II/III prospective, randomized double-blind, placebo controlled trial.
- In Phase II, patients will be treated with aerosolized albuterol 5.0 mg vs. normal saline (n=40-50)administered every 4 hours for 10 days following randomization or until 24 hours following extubation, whichever occurs first. The protocol stipulates that the 5.0 mg dose will be reduced to 2.5 mg if patients exceed defined heart rate limits.
- In Phase III, the 5.0 mg dose will be used unless there is evidence that this dose has an unacceptable safety profile or dose reductions for tachycardia occur in a large fraction of patients. In that case, a lower dose of 2.5 mg will be used.
- Patients will be followed for 90 days or until discharge from the hospital to home with unassisted breathing whichever occurs first.
- Conditions
- Respiratory Distress Syndrome, Adult
- Being tested
- Albuterol Sulfate, Mini-Bronchoalveolar Lavage (BAL), Placebo
- Keywords
- Acute Lung Injury, Acute Respiratory Distress Syndrome, Albuterol, Aerosolized, Critical Care, Ventilator
- Medical subject headings
- Respiratory Distress Syndrome, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Albuterol SulfateDrug
Also called 0.9% sodium chloride
Albuterol sulfate, USP, solution for inhalation will be diluted as follows:
- The full dose of 5.0 mg will be diluted into 2.0 ml of sterile normal saline solution.
- The reduced dose of 2.5 mg will be diluted into 2.5 ml of sterile normal saline solution.
A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization. The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first.
Mini-Bronchoalveolar Lavage (BAL)Procedure or surgery
Also called Combicath
The mini-BAL procedure involves blind specimen sampling from distal airspaces. Specimens are obtained with the Combicath (Plastimed) catheter. The procedure will be done on study days 0 and 3
PlaceboDrug
Also called 0.9% sodium chloride
Placebo aerosol will consist of 3.0 ml of identical appearing sterile 0.9 % sodium chloride without preservative.
A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization (e.g.: throughout the inspiratory and expiratory cycle).
The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Albuterol Sulfate | Active comparator | Not described Receives: Drug: Albuterol Sulfate; Procedure: Mini-Bronchoalveolar Lavage (BAL) |
| Placebo | Placebo comparator | Not described Receives: Procedure: Mini-Bronchoalveolar Lavage (BAL); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Ventilator Free Days (VFD)
Ventilator-free days (VFDs) is defined as the number of days from randomization to Day 28 after achieving unassisted breathing for patients who maintained unassisted breathing for at least two consecutive calendar days. If a patient achieved unassisted breathing, subsequently required additional assisted breathing, and once again achieved unassisted breathing, we counted only the VFDs after beginning the final period of unassisted breathing. Patients who died before Day 28 were assigned zero VFDs.
Measured: Determined 28 days after a subject entered the study
Secondary outcomes (9)
Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 60
Success for this efficacy variable was defined as being alive on study day 60 or having been discharged alive off mechanical ventilation from the study hospital (or subsequent hospital) to the subject's original place of residence. Those subjects alive in hospital at day 60 were considered to have survived.
Measured: Determined 60 days after a subject entered the study
Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 90
Success for this efficacy variable was defined as being alive on study day 90 or having been discharged alive off mechanical ventilation from the study hospital (or subsequent hospital) to the subject's original place of residence. Those participants who still remained in the hospital at 90 days after randomization were considered to have survived.
Measured: Determined 90 days after a subject entered the study
Number of ICU-free Days at 28 Days After Randomization
ICU (intensive care unit)-free days was defined as the number of days a subject was out of the ICU during study hospitalization from date of randomization up to study day 28. All incidences of ICU admission and discharge during the study hospitalization were captured. Any portion of a calendar day that a subject was in the ICU was counted as an ICU day.
Measured: Determined 28 days after a subject entered the study
Number of Organ Failure-free Days at Day 28 Following Randomization
Subjects were followed for development of organ failures from date of randomization to hospital discharge or study day 28, whichever was first. Organ failure was defined as present on any calendar day when the most abnormal vital signs or clinically available lab value met the definition of clinically significant organ failure according to the Brussels Organ Failure Table. Each day a patient was alive and free of a given clinically significant organ failure was scored as a failure-free day. The worst value for a calendar day was captured (lowest systolic BP, platelet count and highest creatinine and bilirubin values). Specific definitions of organ failure were: cardiovascular-systolic BP less than or equal to 90 mmHg or on a vasopressor; coagulation-platelet count less than or equal to 80 x 1000/mm3; Renal-creatinine less than or equal to 2.0 mg/dL; Hepatic-bilirubin less than or equal to 2.0 mg/dL.
Measured: Daily from baseline to study day 28
Ventilator Free Days to Day 28 in the Subset of Participants With ARDS
Difference in the main outcome Ventilator Free Days to study day 28 was calculated for the subset of patients with ARDS (defined as a PaO2/FiO2 ratio of less than or equal to 200). P/F ratio is an index of the effectiveness of arterial oxygenation that corresponds to the ratio of partial pressure of arterial O2 to the fraction of inspired O2. VFD to Day 28 is defined as the number of days from the end of ventilation to day 28 in patients who maintained unassisted breathing for at least two consecutive calendar days. Patients who died before day 28 were assigned a VFD count of zero. If a patient returned to assisted breathing, subsequently required assisted breathing, and once again achieved unassisted breathing, only the VFDs after beginning the final period of unassisted breathing were counted. An increase in the number of VFDs was considered a positive result.
Measured: Determined 28 days after a subject entered the study
Hospital Mortality to Day 60 in the Subset of Participants With ARDS
Difference in the main outcome mortality to study day 60 was calculated for the subset of patients with ARDS (defined as a PaO2/FiO2 ratio of less than or equal to 200) prior to randomization. P/F ratio is an index of the effectiveness of arterial oxygenation that corresponds to the ratio of partial pressure of arterial O2 to the fraction of inspired O2.
Measured: Determined 60 days after a subject entered the study
Ventilator Free Days to Day 28 in the Subset of Patients With Baseline Shock
Difference in the main outcome Ventilator Free Days to study day 28 was calculated for the subset of patients who were in shock at the time of randomization. Shock was defined as mean arterial pressure<60 or the need for vasopressors (except dopamine <6 ug/kg/min).
Measured: Determined 28 days after a subject entered the study
Hospital Mortality up to Day 60 in Subjects With Baseline Shock
Difference in the main outcome hospital mortality to study day 60 was calculated for the subset of patients who were in shock at the time of randomization. Shock was defined as mean arterial pressure<60 or the need for vasopressors (except dopamine <6 ug/kg/min).
Measured: Determined 60 days after a subject entered the study
Plasma Levels of IL-6 and IL-8 on Study Day 3
Biologic end-points were selected that would provide mechanistic insight into how albuterol improved lung function. Concentrations of two proinflammatory cytokines, interleukin 6 and 8 (IL-6 and IL-8), were measured. Plasma was collected and cytokine levels were measured at baseline and 3 days after randomization. IL-6 and IL-8 levels were normalized using log transformation. Wilcoxon's test was used to compare mean log-transformed interleukin levels per day and a mixed-effects model was fit to compare the slopes.
Measured: Measured at baseline and 3 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2007 (estimated)
- Study startAug 2007
- Primary completionSep 2008
- Study completionNov 2008
Why it stopped: Stopped for futility by DSMB
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome, AdultStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 282 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael A. Matthay, MD, Principal investigator, University of California, San FranciscoRoy Brower, MD, Study chair, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00434993
- Sponsor's protocol ID
- 474
- Other IDs
- N01HR056179, HHSN268200536179C
- Acronym
- ALTA
- Status last verified
- Dec 2016
- First submitted
- 29 Jan 2007
- Last updated
- 10 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: a deidentified database of the ALVEOLI study is available through BioLINCC
Publications
Brown SM, Wilson E, Presson AP, Zhang C, Dinglas VD, Greene T, Hopkins RO, Needham DM; with the National Institutes of Health NHLBI ARDS Network. Predictors of 6-month health utility outcomes in survivors of acute respiratory distress syndrome. Thorax. 2017 Apr;72(4):311-317. doi: 10.1136/thoraxjnl-2016-208560. Epub 2016 Jul 20.
PubMed 27440140Ambrus DB, Benjamin EJ, Bajwa EK, Hibbert KA, Walkey AJ. Risk factors and outcomes associated with new-onset atrial fibrillation during acute respiratory distress syndrome. J Crit Care. 2015 Oct;30(5):994-7. doi: 10.1016/j.jcrc.2015.06.003. Epub 2015 Jun 16.
PubMed 26138630National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, Kallet RH, Liu KD, MacIntyre N, Moss M, Schoenfeld D, Steingrub J, Thompson BT. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011 Sep 1;184(5):561-8. doi: 10.1164/rccm.201012-2090OC.
PubMed 21562125
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo in Acute Lung Injury
- ClinicalTrials.gov ID
- NCT00434993
- Acronym / sponsor ID
- ALTA / 474
- Conditions
- Respiratory Distress Syndrome, Adult
- Keywords
- Acute Lung Injury, Acute Respiratory Distress Syndrome, Albuterol, Aerosolized, Critical Care, Ventilator
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stopped for futility by DSMB
- Enrolment
- 282 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 2007
- Primary completion
- Sep 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 14 Feb 2007 (estimated)
- Results
- Posted 15 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute Respiratory Distress Syndrome (ARDS) and a lesser condition that occurs prior to ARDS, Acute Lung Injury (ALI), are medical conditions that occur when there is severe inflammation and increased fluids (edema) in both lungs, making it hard for the lungs to function properly. Patients with these conditions require treatment that includes the use of a breathing machine (ventilator). The purpose of this study is to find out whether giving albuterol (a drug commonly used in asthmatics) or not giving albuterol to patients with ALI or ARDS makes a difference in how long it takes for a patient to be able to breath without the ventilator.
Detailed description
Aerosolized beta-2 agonist therapy is anticipated to diminish the formation of lung edema, enhance clearance of lung edema and decrease pulmonary inflammation in patients with acute lung injury. Because beta-2 agonists have been shown to reduce permeability induced lung injury, it is anticipated that the severity of lung injury will be reduced by aerosolized beta-2 agonist therapy. The therapy may work by enhancing resolution of pulmonary edema by upregulating alveolar epithelial fluid transport mechanisms that will in turn enhance the clearance of alveolar edema. A reduction in the severity of lung injury and the quantity of alveolar edema should result in earlier extubation and more ventilator free days, improved pulmonary oxygen uptake, and improved lung compliance.
Study design: phase II/III prospective, randomized double-blind, placebo controlled trial.
- In Phase II, patients will be treated with aerosolized albuterol 5.0 mg vs. normal saline (n=40-50)administered every 4 hours for 10 days following randomization or until 24 hours following extubation, whichever occurs first. The protocol stipulates that the 5.0 mg dose will be reduced to 2.5 mg if patients exceed defined heart rate limits.
- In Phase III, the 5.0 mg dose will be used unless there is evidence that this dose has an unacceptable safety profile or dose reductions for tachycardia occur in a large fraction of patients. In that case, a lower dose of 2.5 mg will be used.
- Patients will be followed for 90 days or until discharge from the hospital to home with unassisted breathing whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albuterol Sulfate | Active comparator | Drug: Albuterol Sulfate, Procedure: Mini-Bronchoalveolar Lavage (BAL) |
| Placebo | Placebo comparator | Procedure: Mini-Bronchoalveolar Lavage (BAL), Drug: Placebo |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Must meet the following three criteria within a 24-hour period:
- No clinical evidence of left-sided cardiac failure to account for bilateral pulmonary infiltrates
Key exclusion criteria (22 listed)
- Greater than 48 hours since all inclusion criteria are met
- Neuromuscular disease that impairs ability to ventilate without assistance, (e.g., cervical spinal cord injury at level C5 or higher spinal cord injury amyotrophic lateral sclerosis, Guillain-Barré syndrome or myasthenia gravis)
- Pregnant or breast-feeding
- Severe chronic respiratory disease (i.e., chronic hypercapnia [PaCO2 greater than 45 mmHg], chronic hypoxemia [PaO2 less than 55 mmHg on FiO2 = 0.21], hospitalization within the last 6 months for respiratory failure [PaCO2 greater than 50 mm Hg and/or PaO2 less than 55 mmHg on 0.21 FiO2], secondary polycythemia, severe pulmonary hypertension [mean PAP (pulmonary artery pressure) greater than 40 mmHg], or ventilator dependency)
- Burns over greater than 40% of total body surface area
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 |
|---|---|---|
| Albuterol SulfateAlso: 0.9% sodium chlorideAlbuterol sulfate, USP, solution for inhalation will be diluted as follows: * The full dose of 5.0 mg will be diluted into 2.0 ml of sterile normal saline solution. * The reduced dose of 2.5 mg will be diluted into 2.5 ml of sterile normal saline solution. A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization. The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first. | Drug | Albuterol Sulfate |
| Mini-Bronchoalveolar Lavage (BAL)Also: CombicathThe mini-BAL procedure involves blind specimen sampling from distal airspaces. Specimens are obtained with the Combicath (Plastimed) catheter. The procedure will be done on study days 0 and 3 | Procedure or surgery | Albuterol Sulfate, Placebo |
| PlaceboAlso: 0.9% sodium chloridePlacebo aerosol will consist of 3.0 ml of identical appearing sterile 0.9 % sodium chloride without preservative. A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization (e.g.: throughout the inspiratory and expiratory cycle). The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first. | Drug | Placebo |
Primary outcome
Number of Ventilator Free Days (VFD)
Time frame: Determined 28 days after a subject entered the study
Ventilator-free days (VFDs) is defined as the number of days from randomization to Day 28 after achieving unassisted breathing for patients who maintained unassisted breathing for at least two consecutive calendar days. If a patient achieved unassisted breathing, subsequently required additional assisted breathing, and once again achieved unassisted breathing, we counted only the VFDs after beginning the final period of unassisted breathing. Patients who died before Day 28 were assigned zero VFDs.
9 secondary outcomes
Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 60
Time frame: Determined 60 days after a subject entered the study
Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 90
Time frame: Determined 90 days after a subject entered the study
Number of ICU-free Days at 28 Days After Randomization
Time frame: Determined 28 days after a subject entered the study
Number of Organ Failure-free Days at Day 28 Following Randomization
Time frame: Daily from baseline to study day 28
Ventilator Free Days to Day 28 in the Subset of Participants With ARDS
Time frame: Determined 28 days after a subject entered the study
Hospital Mortality to Day 60 in the Subset of Participants With ARDS
Time frame: Determined 60 days after a subject entered the study
Ventilator Free Days to Day 28 in the Subset of Patients With Baseline Shock
Time frame: Determined 28 days after a subject entered the study
Hospital Mortality up to Day 60 in Subjects With Baseline Shock
Time frame: Determined 60 days after a subject entered the study
Plasma Levels of IL-6 and IL-8 on Study Day 3
Time frame: Measured at baseline and 3 days after randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27440140Brown SM, Wilson E, Presson AP, Zhang C, Dinglas VD, Greene T, Hopkins RO, Needham DM; with the National Institutes of Health NHLBI ARDS Network. Predictors of 6-month health utility outcomes in survivors of acute respiratory distress syndrome. Thorax. 2017 Apr;72(4):311-317. doi: 10.1136/thoraxjnl-2016-208560. Epub 2016 Jul 20.
- Derived from this study: PubMed 26138630Ambrus DB, Benjamin EJ, Bajwa EK, Hibbert KA, Walkey AJ. Risk factors and outcomes associated with new-onset atrial fibrillation during acute respiratory distress syndrome. J Crit Care. 2015 Oct;30(5):994-7. doi: 10.1016/j.jcrc.2015.06.003. Epub 2015 Jun 16.
- Derived from this study: PubMed 21562125National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, Kallet RH, Liu KD, MacIntyre N, Moss M, Schoenfeld D, Steingrub J, Thompson BT. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011 Sep 1;184(5):561-8. doi: 10.1164/rccm.201012-2090OC.
- NHLBI Acute Respiratory Distress Syndrome Network WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. a deidentified database of the ALVEOLI study is available through BioLINCC
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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.
Michael A. Matthay, MD principal investigator
University of California, San Francisco
Roy Brower, MD study chair
Johns Hopkins University
40 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Albuterol Sulfate and Mini-Bronchoalveolar Lavage (BAL) in people with Respiratory Distress Syndrome, Adult, run by National Heart, Lung, and Blood Institute (NHLBI) at 40 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 5 inclusion and 22 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 10 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 15 Jul 2013). 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?
Number of Ventilator Free Days (VFD) (time frame: Determined 28 days after a subject entered the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00434993, which also lists 3 linked publications.
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 10 Feb 2017.