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Trial record 78 of 857 for:    ALBUTEROL

Drug Study of Albuterol to Treat Acute Lung Injury (ALTA)

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ClinicalTrials.gov Identifier: NCT00434993
Recruitment Status : Terminated (Stopped for futility by DSMB)
First Posted : February 14, 2007
Results First Posted : July 15, 2013
Last Update Posted : February 10, 2017
Sponsor:
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Respiratory Distress Syndrome, Adult
Interventions Drug: Albuterol Sulfate
Procedure: Mini-Bronchoalveolar Lavage (BAL)
Drug: Placebo
Enrollment 282
Recruitment Details The trial was conducted with a combined Phase II/III design to enroll 1000 patients with a safety review performed after 100 subjects were enrolled and interim analysis looks at 250, 500, and 700 subjects. The first subject was entered in August 2007 and the last subject in July of 2008 when the study was stopped for futility at 282 enrolled.
Pre-assignment Details  
Arm/Group Title Albuterol Sulfate Placebo
Hide Arm/Group Description Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours Preservative-free 0.9% sterile sodium chloride every 4 hours
Period Title: Overall Study
Started 152 130
Completed 152 130
Not Completed 0 0
Arm/Group Title Albuterol Sulfate Placebo Total
Hide Arm/Group Description Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours Preservative-free 0.9% sterile sodium chloride every 4 hours Total of all reporting groups
Overall Number of Baseline Participants 152 130 282
Hide Baseline Analysis Population Description
All randomized patients were analyzed.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 130 participants 282 participants
<=18 years
2
   1.3%
3
   2.3%
5
   1.8%
Between 18 and 65 years
111
  73.0%
100
  76.9%
211
  74.8%
>=65 years
39
  25.7%
27
  20.8%
66
  23.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 152 participants 130 participants 282 participants
52.3  (16.4) 50.9  (16.2) 51.6  (16.2)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 130 participants 282 participants
Female
67
  44.1%
59
  45.4%
126
  44.7%
Male
85
  55.9%
71
  54.6%
156
  55.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 152 participants 130 participants 282 participants
152 130 282
1.Primary Outcome
Title Number of Ventilator Free Days (VFD)
Hide Description 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.
Time Frame Determined 28 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
All the intent to treat patients were analyzed. Data was available on all subjects for the primary analysis only.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 152 130
Mean (Standard Error)
Unit of Measure: days
14.4  (0.9) 16.6  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments The trial had a statistical power of 90.7% to detect a 2.25-day increase in VFDs,assuming a SD of 10.5 days. A group sequential design was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments The p-value was not adjusted for multiple comparisons.
Method ANCOVA
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.7 to 0.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.3
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 60
Hide Description 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.
Time Frame Determined 60 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 152 130
Measure Type: Number
Unit of Measure: percentage of participants who died
23.0 17.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.302
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Logistic
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
-4.0 to 14.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 90
Hide Description 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.
Time Frame Determined 90 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 152 130
Measure Type: Number
Unit of Measure: percentage of participants who died
24.3 18.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.261
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Logistic
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-3.7 to 15.4
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of ICU-free Days at 28 Days After Randomization
Hide Description 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.
Time Frame Determined 28 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 152 130
Mean (Standard Error)
Unit of Measure: days
13.5  (0.8) 16.2  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments The p-value was not adjusted for multiple comparisons.
Method ANCOVA
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-4.9 to -0.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Organ Failure-free Days at Day 28 Following Randomization
Hide Description 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.
Time Frame Daily from baseline to study day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 152 130
Mean (Standard Error)
Unit of Measure: days
14.2  (0.9) 15.9  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.226
Comments The p-value was not adjusted for multiple comparisons.
Method ANCOVA
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-4.3 to 0.9
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Ventilator Free Days to Day 28 in the Subset of Participants With ARDS
Hide Description 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.
Time Frame Determined 28 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Patients meeting the criteria for ARDS (pre-randomization PaO2/FiO2 ratio less than or equal to 200) were selected for this subset.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 106 86
Mean (Standard Error)
Unit of Measure: days
14.5  (1.1) 16.8  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-5.3 to 0.6
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Hospital Mortality to Day 60 in the Subset of Participants With ARDS
Hide Description 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.
Time Frame Determined 60 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Patients meeting the criteria for ARDS (pre-randomization PaO2/FiO2 ratio less than or equal to 200) were selected for this subset.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 106 86
Measure Type: Number
Unit of Measure: percentage of participants who died
24.5 16.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.176
Comments [Not Specified]
Method Regression, Logistic
Comments Adjusted for baseline shock.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 8.2
Confidence Interval (2-Sided) 95%
-3.1 to 19.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Ventilator Free Days to Day 28 in the Subset of Patients With Baseline Shock
Hide Description 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).
Time Frame Determined 28 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with protocol defined shock (mean arterial pressure<60 or need for vasopressors except dopamine < 6ug/kg/min) at the time of study entry.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 68 55
Mean (Standard Error)
Unit of Measure: days
10.0  (1.3) 13.9  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.9
Confidence Interval (2-Sided) 95%
-7.8 to -0.0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Hospital Mortality up to Day 60 in Subjects With Baseline Shock
Hide Description 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).
Time Frame Determined 60 days after a subject entered the study
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with protocol defined shock (mean arterial pressure<60 or need for vasopressors except dopamine < 6ug/kg/min) at the time of study entry.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 68 55
Measure Type: Number
Unit of Measure: percentage of participants who died
36.8 27.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.265
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 9.5
Confidence Interval (2-Sided) 95%
-6.9 to 25.9
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Plasma Levels of IL-6 and IL-8 on Study Day 3
Hide Description 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.
Time Frame Measured at baseline and 3 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Not all subjects had available data for secondary analyses and therefor the numbers will be less than the 152 (active) and 130 (placebo) arms.
Arm/Group Title Albuterol Placebo
Hide Arm/Group Description:
Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours
Preservative-free 0.9% sterile sodium chloride every 4 hours
Overall Number of Participants Analyzed 127 110
Log Mean (Standard Deviation)
Unit of Measure: pg/ml
IL6 1.9  (0.6) 1.8  (0.7)
IL8 1.7  (0.5) 1.7  (0.5)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Albuterol Sulfate Placebo
Hide Arm/Group Description Aerosolized albuterol sulfate (5.0 mg dissolved in saline) every 4 hours Preservative-free 0.9% sterile sodium chloride every 4 hours
All-Cause Mortality
Albuterol Sulfate Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Albuterol Sulfate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/152 (0.66%)      1/130 (0.77%)    
Respiratory, thoracic and mediastinal disorders     
Hypoxemia  1  0/152 (0.00%)  0 1/130 (0.77%)  1
Hypoxia  1  1/152 (0.66%)  1 0/130 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, COSTART 5.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Albuterol Sulfate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/152 (13.82%)      15/130 (11.54%)    
Cardiac disorders     
Arrhythmias (clinically important)  1  15/152 (9.87%)  29 8/130 (6.15%)  11
Metabolism and nutrition disorders     
Hypokalemia  1  8/152 (5.26%)  12 7/130 (5.38%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, COSTART 5.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Schoenfeld, ARDSNet CCC PI
Organization: Acute Respiratory Distress Syndrome (ARDS) Network
Phone: 617-726-6111
EMail: dschoenfeld@partners.org
Layout table for additonal information
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00434993     History of Changes
Other Study ID Numbers: 474
N01 HR056179
HHSN268200536179C
First Submitted: January 29, 2007
First Posted: February 14, 2007
Results First Submitted: December 4, 2012
Results First Posted: July 15, 2013
Last Update Posted: February 10, 2017