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A Study to Look at Day to Day Changes in Lung Function in COPD Subjects Taking Albuterol/Salbutamol and Ipratropium

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ClinicalTrials.gov Identifier: NCT01691482
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : December 25, 2013
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Albuterol/salbutamol
Drug: Ipratropium
Enrollment 56
Recruitment Details  
Pre-assignment Details This was a randomized, open-label, two-period cross-over study to evaluate the daily bronchodilator response to albuterol/salbutamol and ipratropium individually and in combination in participants with chronic obstructive pulmonary disease.
Arm/Group Title A/S Then Ipratropium in TP1; Ipratropium Then A/S in TP2 Ipratropium Then A/S in TP1; A/S Then Ipratropium in TP2
Hide Arm/Group Description Participants received albuterol (4 puffs; 90 micrograms [µg] per puff)/salbutamol (A/S) (4 puffs; 100 µg per puff) followed by ipratropium (4 puffs; 20 µg per puff) via a metered-dose inhaler (MDI) during treatment period 1 (TP1) then, ipratropium followed by A/S at the same doses via an MDI in treatment period 2 (TP2). Participants received Ipratropium (4 puffs; 20 µg per puff) followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) (A/S) via a MDI in TP1, then A/S followed by ipratropium at the same doses via an MDI in TP2.
Period Title: Treatment Period 1
Started 28 28
Completed 28 28
Not Completed 0 0
Period Title: Treatment Period 2
Started 28 28
Completed 27 26
Not Completed 1 2
Reason Not Completed
Adverse Event             0             1
Protocol Violation             1             1
Arm/Group Title All Randomized Participants
Hide Arm/Group Description All participants randomized to receive a sequence of either salbutamol (4 puffs; 100 µg per puff) via an MDI and albuterol (4 puffs; 90 µg per puff) followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in TP1 and the same dose of each bronchodilator given in the opposite order in TP2, or ipratropium followed by albuterol/salbutamol in TP1 and the same dose of each bronchodilator given in the opposite order in TP2
Overall Number of Baseline Participants 56
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 56 participants
60.3  (7.42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants
Female
35
  62.5%
Male
21
  37.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 56 participants
African American/African Heritage 4
White 52
1.Primary Outcome
Title Variability in Daily FEV1, Estimated by Coefficient of Variation
Hide Description FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily FEV1 was measured as the fluctuation around the mean FEV1 data collected from Day 1 to Day 10. Variability was measured by the coefficient of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is the difference between the maximum and minimum FEV1 values.
Time Frame up to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: participants in the Intent-to-Treat Population (all participants who were randomized and received at least one bronchodilator in the treatment period) who completed pre- and post- bronchodilator assessments for at least 17 visits, with no more than 3 consecutive missing days
Arm/Group Title Albuterol/Salbutamol Followed by Ipratropium Ipratropium Followed by Albuterol/Salbutamol
Hide Arm/Group Description:
All participants randomized to receive a sequence of albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in either TP1 or TP2.
All participants randomized to receive a sequence of ipratropium (4 puffs; 20 µg per puff) via an MDI followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI in either TP1 or TP2
Overall Number of Participants Analyzed 55 55
Mean (Standard Error)
Unit of Measure: Liters
Pre-dose/non-bronchodilator 0.081  (0.0394) 0.079  (0.0372)
Albuterol/Salbutamol (A/S) alone, 1 hour 0.059  (0.0276) NA [1]   (NA)
A/S followed by ipratropium, 2 hours 0.054  (0.0232) NA [2]   (NA)
Ipratropium alone, 1 hour NA [3]   (NA) 0.072  (0.0406)
Ipratropium followed by A/S, 2 hours NA [4]   (NA) 0.063  (0.0327)
[1]
Participants in this treatment arm received ipratropium as the first bronchodilator; thus, data were not collected for albuterol/salbutamol (A/S) at this time point.
[2]
Participants in this treatment arm received ipratropium followed by A/S; thus, data were not collected for A/S followed by ipratropium.
[3]
Participants in this treatment arm received A/S as the first bronchodilator; thus, data were not collected for ipratropium at this time point.
[4]
Participants in this treatment arm received A/S followed by ipratropium; thus, data were not collected for ipratropium followed by A/S.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.058
Confidence Interval 95%
0.049 to 0.067
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: A/S alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.071
Confidence Interval 95%
0.062 to 0.080
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: ipratropium alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.053
Confidence Interval 95%
0.044 to 0.062
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: A+I. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.062
Confidence Interval 95%
0.053 to 0.071
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: I+A. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
2.Primary Outcome
Title Variability in Daily FEV1, Estimated by Half Range (i.e., Half the Difference Between Maximum and Minimum Values)
Hide Description FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily FEV1 was measured as the fluctuation around the mean FEV1 data collected from Day 1 to Day 10. Variability was measured by the coefficient of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is half the difference between the maximum and minimum FEV1 values.
Time Frame up to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Albuterol/Salbutamol Followed by Ipratropium Ipratropium Followed by Albuterol/Salbutamol
Hide Arm/Group Description:
All participants randomized to receive a sequence of albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in either TP1 or TP2.
All participants randomized to receive a sequence of ipratropium (4 puffs; 20 µg per puff) via an MDI followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI in either TP1 or TP2
Overall Number of Participants Analyzed 55 55
Mean (Standard Error)
Unit of Measure: Liters
Pre-dose/non-bronchodilator 0.136  (0.0627) 0.135  (0.0780)
Albuterol/Salbutamol (A/S) alone, 1 hour 0.125  (0.0525) NA [1]   (NA)
A/S followed by ipratropium, 2 hours 0.122  (0.0542) NA [2]   (NA)
Ipratropium alone, 1 hour NA [3]   (NA) 0.145  (0.0805)
Ipratropium followed by A/S, 2 hours NA [4]   (NA) 0.137  (0.0726)
[1]
Participants in this treatment arm received ipratropium as the first bronchodilator; thus, data were not collected for albuterol/salbutamol (A/S) at this time point.
[2]
Participants in this treatment arm received ipratropium followed by A/S; thus, data were not collected for A/S followed by ipratropium.
[3]
Participants in this treatment arm received A/S as the first bronchodilator; thus, data were not collected for ipratropium at this time point.
[4]
Participants in this treatment arm received A/S followed by ipratropium; thus, data were not collected for ipratropium followed by A/S.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.058
Confidence Interval 95%
0.049 to 0.067
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: A/S alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.071
Confidence Interval 95%
0.062 to 0.080
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: ipratropium alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.053
Confidence Interval 95%
0.044 to 0.062
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0046
Estimation Comments Treatment: A+I. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.062
Confidence Interval 95%
0.053 to 0.071
Estimation Comments Treatment: I+A. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), FEV1 Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
3.Secondary Outcome
Title The Maximal Bronchodilator Response for the First Administered Agent
Hide Description The maximal bronchodilator response for the first administered agent is defined as the FEV1 (the maximal amount of air that can be forcefully exhaled in one second) 1 hour post-dose of the first bronchodilator minus the pre-dose. The maximal bronchodilator response for the second agent is defined as the FEV1 1 hour post-dose of the second bronchodilator minus the FEV1 at 1 hour post-dose of the first bronchodilator. The maximal bronchodilator response for the combination is defined as the FEV1 (the maximal amount of air that can be forcefully exhaled in one second) at 1 hour post-administration of the second bronchodilator minus the corresponding pre-dose FEV1. Derived FEV1 response is FEV1 change from 0 hours (0H) for the first agent assessment (at 1 hour [1H]); change from 1H for the second agent assessment (at 2 hours [2H]); and change from 0H for the combination assessment (at 2H). Data were adjusted for FEV1, smoking status, and center.
Time Frame up to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title All Randomized Participants
Hide Arm/Group Description:
All participants randomized to receive a sequence of either salbutamol (4 puffs; 100 µg per puff) via an MDI and albuterol (4 puffs; 90 µg per puff) followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in TP1 and the same dose of each bronchodilator given in the opposite order in TP2, or ipratropium followed by albuterol/salbutamol in TP1 and the same dose of each bronchodilator given in the opposite order in TP2
Overall Number of Participants Analyzed 55
Least Squares Mean (Standard Error)
Unit of Measure: Liters
First agent, albuterol/salbutamol (A/S) 0.269  (0.0174)
First agent, ipratropium 0.243  (0.0174)
Second agent, A/S 0.094  (0.0123)
Second agent, ipratropium 0.094  (0.0123)
A/S followed by ipratropium 0.363  (0.0200)
Ipratropium followed by A/S 0.337  (0.0200)
4.Secondary Outcome
Title Percentage of Days for Which Participants Achieved a >=12% and 200 Milliliter (mL) Increase From Baseline in FEV1
Hide Description FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours).
Time Frame up to 35 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Albuterol/Salbutamol Followed by Ipratropium Ipratropium Follwed by Albuterol/Salbutamol
Hide Arm/Group Description:
All participants randomized to receive a sequence of albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in either TP1 or TP2.
All participants randomized to receive a sequence of ipratropium (4 puffs; 20 µg per puff) via an MDI followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI in either TP1 or TP2
Overall Number of Participants Analyzed 55 55
Mean (Standard Deviation)
Unit of Measure: percentage of days
Albuterol/Salbutamol (A/S) alone, 1 hour 58.4  (38.26) NA [1]   (NA)
A/S followed by ipratropium, 2 hours 71.7  (35.51) NA [2]   (NA)
Ipratropium alone, 1 hour NA [3]   (NA) 55.4  (39.34)
Ipratropium followed by A/S, 2 hours NA [4]   (NA) 69.1  (36.82)
[1]
Participants in this treatment arm received ipratropium as the first bronchodilator; thus, data were not collected for albuterol/salbutamol (A/S) at this time point.
[2]
Participants in this treatment arm received ipratropium followed by A/S; thus, data were not collected for A/S followed by ipratropium.
[3]
Participants in this treatment arm received A/S as the first bronchodilator; thus, data were not collected for ipratropium at this time point.
[4]
Participants in this treatment arm received A/S followed by ipratropium; thus, data were not collected for ipratropium followed by A/S.
5.Secondary Outcome
Title Percentage of Days for Which Participants Achieved a Threshold Increase From Baseline in FEV1 of 100 mL, 200 mL, and 250 mL
Hide Description FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours).
Time Frame up to 35 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Albuterol/Salbutamol Followed by Ipratropium Ipratropium Follwed by Albuterol/Salbutamol
Hide Arm/Group Description:
All participants randomized to receive a sequence of albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in either TP1 or TP2.
All participants randomized to receive a sequence of ipratropium (4 puffs; 20 µg per puff) via an MDI followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI in either TP1 or TP2
Overall Number of Participants Analyzed 55 55
Mean (Standard Deviation)
Unit of Measure: percentage of days
A/S alone, 1 hour, 100 mL 81.6  (31.35) NA [1]   (NA)
A/S followed by ipratropium, 2 hours, 100 mL 85.2  (29.92) NA [2]   (NA)
Ipratropium alone, 1 hour, 100 mL NA [3]   (NA) 72.9  (38.06)
Ipratropium followed by A/S, 2 hours, 100 mL NA [4]   (NA) 81.2  (33.46)
A/S alone, 1 hour, 200 mL 59.2  (38.20) NA [1]   (NA)
A/S followed by ipratropium, 2 hours, 200 mL 72.7  (35.25) NA [2]   (NA)
Ipratropium alone, 1 hour, 200 mL NA [3]   (NA) 56.0  (39.54)
Ipratropium followed by A/S, 2 hours, 200 mL NA [4]   (NA) 70.5  (36.23)
A/S alone, 1 hour, 250 mL 45.9  (38.85) NA [1]   (NA)
A/S followed by ipratropium, 2 hours, 250 mL 64.0  (39.08) NA [2]   (NA)
Ipratropium alone, 1 hour, 250 mL NA [3]   (NA) 45.8  (36.94)
Ipratropium followed by A/S, 2 hours, 250 mL NA [4]   (NA) 59.6  (38.19)
[1]
Participants in this treatment arm received ipratropium as the first bronchodilator; thus, data were not collected for albuterol/salbutamol (A/S) at this time point.
[2]
Participants in this treatment arm received ipratropium followed by A/S; thus, data were not collected for A/S followed by ipratropium.
[3]
Participants in this treatment arm received A/S as the first bronchodilator; thus, data were not collected for ipratropium at this time point.
[4]
Participants in this treatment arm received A/S followed by ipratropium; thus, data were not collected for ipratropium followed by A/S.
6.Secondary Outcome
Title Variability in Daily Inspiratory Capacity (IC), Estimated by Coefficient of Variation
Hide Description IC is the the total amount of air that can be drawn into the lungs after normal expiration. During each study period, pre- and post-bronchodilator spirometry for evaluation of IC was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily IC was measured as the fluctuation around the mean IC data collected from Day 1 to Day 10. Variability was measured by the coefficent of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is the difference between the maximum and minimum IC values.
Time Frame up to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Albuterol/Salbutamol Followed by Ipratropium Ipratropium Followed by Albuterol/Salbutamol
Hide Arm/Group Description:
All participants randomized to receive a sequence of albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in either TP1 or TP2.
All participants randomized to receive a sequence of ipratropium (4 puffs; 20 µg per puff) via an MDI followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI in either TP1 or TP2
Overall Number of Participants Analyzed 55 55
Mean (Standard Deviation)
Unit of Measure: Liters
Pre-dose/non-bronchodilator 0.078  (0.0305) 0.083  (0.0374)
Albuterol/Salbutamol (A/S) alone, 1 hour 0.069  (0.0310) NA [1]   (NA)
A/S followed by ipratropium (A+I), 2 hours 0.070  (0.0373) NA [2]   (NA)
Ipratropium alone, 1 hour NA [3]   (NA) 0.072  (0.0353)
Ipratropium followed by A/S (I+A), 2 hours NA [4]   (NA) 0.066  (0.0307)
[1]
Participants in this treatment arm received ipratropium as the first bronchodilator; thus, data were not collected for albuterol/salbutamol (A/S) at this time point.
[2]
Participants in this treatment arm received ipratropium followed by A/S; thus, data were not collected for A/S followed by ipratropium.
[3]
Participants in this treatment arm received A/S as the first bronchodilator; thus, data were not collected for ipratropium at this time point.
[4]
Participants in this treatment arm received A/S followed by ipratropium; thus, data were not collected for ipratropium followed by A/S.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.067
Confidence Interval 95%
0.058 to 0.076
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0045
Estimation Comments Treatment: A/S alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.070
Confidence Interval 95%
0.061 to 0.079
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0045
Estimation Comments Treatment: ipratropium alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.069
Confidence Interval 95%
0.060 to 0.078
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0045
Estimation Comments Treatment: A+I. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.064
Confidence Interval 95%
0.055 to 0.073
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0045
Estimation Comments Treatment: I+A. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
7.Secondary Outcome
Title Variability in Daily IC, Estimated by Half Range (i.e., Half the Difference Between Maximum and Minimum)
Hide Description IC is the the total amount of air that can be drawn into the lungs after normal expiration. During each study period, pre- and post-bronchodilator spirometry for evaluation of IC was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily IC was measured as the fluctuation around the mean IC data collected from Day 1 to Day 10. Variability was measured by the coefficent of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is half the difference between the maximum and minimum IC values.
Time Frame up to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population
Arm/Group Title Albuterol/Salbutamol Followed by Ipratropium Ipratropium Followed by Albuterol/Salbutamol
Hide Arm/Group Description:
All participants randomized to receive a sequence of albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in either TP1 or TP2.
All participants randomized to receive a sequence of ipratropium (4 puffs; 20 µg per puff) via an MDI followed by albuterol (4 puffs; 90 µg per puff)/salbutamol (4 puffs; 100 µg per puff) via an MDI in either TP1 or TP2
Overall Number of Participants Analyzed 55 55
Mean (Standard Deviation)
Unit of Measure: Liters
Pre-dose/non-bronchodilator 0.225  (0.1017) 0.236  (0.1166)
Albuterol/Salbutamol (A/S) alone, 1 hour 0.229  (0.1004) NA [1]   (NA)
A/S followed by ipratropium, 2 hours 0.233  (0.1132) NA [2]   (NA)
Ipratropium alone, 1 hour NA [3]   (NA) 0.235  (0.1026)
Ipratropium followed by A/S, 2 hours NA [4]   (NA) 0.221  (0.1066)
[1]
Participants in this treatment arm received ipratropium as the first bronchodilator; thus, data were not collected for albuterol/salbutamol (A/S) at this time point.
[2]
Participants in this treatment arm received ipratropium followed by A/S; thus, data were not collected for A/S followed by ipratropium.
[3]
Participants in this treatment arm received A/S as the first bronchodilator; thus, data were not collected for ipratropium at this time point.
[4]
Participants in this treatment arm received A/S followed by ipratropium; thus, data were not collected for ipratropium followed by A/S.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.228
Confidence Interval 95%
0.200 to 0.255
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0140
Estimation Comments Treatment: A/S alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.231
Confidence Interval 95%
0.203 to 0.258
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0140
Estimation Comments Treatment: ipratropium alone. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Albuterol/Salbutamol Followed by Ipratropium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.232
Confidence Interval 95%
0.204 to 0.259
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0140
Estimation Comments Treatment: A+I. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ipratropium Followed by Albuterol/Salbutamol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Mean
Estimated Value 0.217
Confidence Interval 95%
0.190 to 0.245
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0140
Estimation Comments Treatment: I+A. A mixed model analysis, with period, treatment (A+I, I+A, Albuterol alone, Ipratropium alone), IC Baseline, smoking status at Screening, and center fitted as fixed effects and participant as a random effect was used.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Randomized Participants
Hide Arm/Group Description All participants randomized to receive a sequence of either salbutamol (4 puffs; 100 µg per puff) via an MDI and albuterol (4 puffs; 90 µg per puff) followed by ipratropium (4 puffs; 20 µg per puff) via an MDI in TP1 and the same dose of each bronchodilator given in the opposite order in TP2, or ipratropium followed by albuterol/salbutamol in TP1 and the same dose of each bronchodilator given in the opposite order in TP2
All-Cause Mortality
All Randomized Participants
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Randomized Participants
Affected / at Risk (%)
Total   1/56 (1.79%) 
General disorders   
Death  1  1/56 (1.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Randomized Participants
Affected / at Risk (%)
Total   16/56 (28.57%) 
Gastrointestinal disorders   
Abdominal pain upper  1  1/56 (1.79%) 
Diarrhoea  1  1/56 (1.79%) 
Toothache  1  1/56 (1.79%) 
Vomiting  1  1/56 (1.79%) 
General disorders   
Chest discomfort  1  1/56 (1.79%) 
Influenza like illness  1  1/56 (1.79%) 
Oedema peripheral  1  1/56 (1.79%) 
Infections and infestations   
Bacterial infection  1  1/56 (1.79%) 
Herpes zoster  1  1/56 (1.79%) 
Nasopharyngitis  1  1/56 (1.79%) 
Rhinitis  1  1/56 (1.79%) 
Injury, poisoning and procedural complications   
Excoriation  1  1/56 (1.79%) 
Fall  1  1/56 (1.79%) 
Muscle strain  1  1/56 (1.79%) 
Radius fracture  1  1/56 (1.79%) 
Tooth fracture  1  1/56 (1.79%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/56 (1.79%) 
Joint swelling  1  1/56 (1.79%) 
Muscle spasms  1  1/56 (1.79%) 
Nervous system disorders   
Headache  1  4/56 (7.14%) 
Dizziness  1  1/56 (1.79%) 
Dysgeusia  1  1/56 (1.79%) 
Renal and urinary disorders   
Haematuria  1  1/56 (1.79%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/56 (1.79%) 
Epistaxis  1  1/56 (1.79%) 
Increased upper airway secretion  1  1/56 (1.79%) 
Painful respiration  1  1/56 (1.79%) 
Sneezing  1  1/56 (1.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01691482     History of Changes
Other Study ID Numbers: 114956
First Submitted: September 20, 2012
First Posted: September 24, 2012
Results First Submitted: June 12, 2013
Results First Posted: December 25, 2013
Last Update Posted: June 20, 2018