Pulmonary Disease, Chronic ObstructivePhase 4NCT00984659
Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease
A Phase 4 study testing Fluticasone propionate/salmeterol combination product and Salmeterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 39 sites in United States.
Trial summary
The purpose of this study is to evaluate a new questionnaire to capture the patient experience of COPD. The information collected will be used to validate the Shortness of Breath with Daily Activities Questionnaire. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Fluticasone propionate/salmeterol combination product and Salmeterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 366 participants
- Where
- 39 sitesUnited States
- Study dates
- 29 Oct 2009to 1 Jul 2010
- Phase
- Phase 4
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 40 years of age
- Established clinical history of COPD by ATS/ERS definition
- Former or current smoker > 10 pack years
- Evidence of dyspnea
Who cannot join
- Has a respiratory disorder other than COPD
- Cancer not in complete clinical remission
- Clinically significant cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine, or hematological abnormalities that are uncontrolled
Trial locations and contacts
39 sites in 1 country.
39 sites in 1 country
United States39 sites
GSK Investigational Site
Abingdon, Virginia, 24210
GSK Investigational Site
Canton, Ohio, 44718
GSK Investigational Site
Charleston, South Carolina, 29406-7108
GSK Investigational Site
Charlotte, North Carolina, 28207
GSK Investigational Site
Chester, South Carolina, 29706
GSK Investigational Site
Cincinnati, Ohio, 45231
GSK Investigational Site
Clinton, South Carolina, 29325
GSK Investigational Site
Decatur, Georgia, 30033
GSK Investigational Site
Easley, South Carolina, 29640
GSK Investigational Site
Elizabeth City, North Carolina, 27909
GSK Investigational Site
Erie, Pennsylvania, 16508
GSK Investigational Site
Evansville, Indiana, 47710
GSK Investigational Site
Evansville, Indiana, 47714
GSK Investigational Site
Gaffney, South Carolina, 29340
GSK Investigational Site
Greenwood, South Carolina, 29646
GSK Investigational Site
Houston, Texas, 77054
GSK Investigational Site
Jasper, Alabama, 35501
GSK Investigational Site
Johnson City, Tennessee, 37601
GSK Investigational Site
Lake Oswego, Oregon, 97035
GSK Investigational Site
Lawrenceville, Georgia, 30046
GSK Investigational Site
Los Angeles, California, 90095-1690
GSK Investigational Site
Madisonville, Kentucky, 42431
GSK Investigational Site
Mobile, Alabama, 36608
GSK Investigational Site
New Braunfels, Texas, 78130
GSK Investigational Site
New Orleans, Louisiana, 70115
GSK Investigational Site
Philadelphia, Pennsylvania, 19140
GSK Investigational Site
Portland, Oregon, 97213
GSK Investigational Site
Richmond, Virginia, 23229
GSK Investigational Site
Riverside, California, 92506
GSK Investigational Site
Seneca, South Carolina, 29678
GSK Investigational Site
South Bend, Indiana, 46617
GSK Investigational Site
Spartanburg, South Carolina, 29303
GSK Investigational Site
Spokane, Washington, 99204
GSK Investigational Site
St Louis, Missouri, 63141
GSK Investigational Site
Stamford, Connecticut, 06902
GSK Investigational Site
Summit, New Jersey, 07091
GSK Investigational Site
Sunset, Louisiana, 70584
GSK Investigational Site
Tamarac, Florida, 33321
GSK Investigational Site
Wheat Ridge, Colorado, 80033
About this study
The purpose of this study is to evaluate a new questionnaire to capture the patient experience of COPD. The information collected will be used to validate the Shortness of Breath with Daily Activities Questionnaire.
Read the detailed description
Dyspnea, referred to by patients as "shortness of breath" or "breathlessness," is frequently associated with decreases in functional status, quality of life, and disabilities. Currently available questionnaires do not specifically address the shortness of breath component of COPD. The development of a patient reported outcome questionnaire that will specifically assess Shortness of Breath with Daily Activities (SOBDA) in patients with COPD is needed.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Fluticasone propionate/salmeterol combination product, Salmeterol, Placebo
- Keywords
- Pulmonary Disease, Chronic Obstructive, Dyspnea
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluticasone propionate/salmeterol combination productDrug
Fluticasone propionate/salmeterol combination product 250/50mcg DISKUS twice a day for 8 weeks
SalmeterolDrug
Salmeterol 50mcg DISKUS twice a day for 8 weeks
PlaceboDrug
Placebo DISKUS twice a day for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| FSC | Experimental | Fluticasone propionate/salmeterol combination product 250/50mcg DISKUS twice a day Receives: Drug: Fluticasone propionate/salmeterol combination product |
| SAL | Experimental | Salmeterol 50mcg DISKUS twice a day Receives: Drug: Salmeterol |
| Placebo | Placebo comparator | Placebo DISKUS twice a day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Internal Consistency (IC) of the Shortness of Breath With Daily Activities (SOBDA) Questionnaire in Participants With Chronic Obstructive Pulmonary Disease (COPD) Assessed as Cronbach's Alpha Value
Cronbach's alpha (CA) is a measure of the IC of the 13-item SOBDA questionnaire (completed via electronic diary by a sample of participants). It is the ratio of the variance (var.) of the sum of the individual scores and the var. of the total score. The var. of the sum of a group of independent variables is the sum of their var.; thus, if the variables are positively correlated, the var. of the sum will be increased. If the items making up the score are identical and so perfectly correlated, CA=1. If the items are independent, CA=0. Higher scores indicate a more reliable (precise) instrument.
Measured: Day 1 of the 2-week Run-in Period
Test-retest Reliability (T-RR) of SOBDA Scores Measured as the Difference in the SOBDA Weekly Score Between Week 1 and Week 2 of the 2-week Run-in Period
T-RR=stability during repeat measures over time in a stable population. SOBDA score was determined by the 13-item (it.) scoring algorithm, assigning a weekly mean score of 1-4 (higher scores=more severe breathlessness with daily activities) based on the mean of 7 days of data (or >=4 days). Daily total score is computed from the mean of the participant's (par.) scores on the 13 it. (>=7 it. must have non-missing responses). Only scores of stable par. (indicating no change [score=3] on the par.-completed Patient Global Assessment of Change [PGAC]; 1 [ much worse] to 5 [much better]) were used.
Measured: Week 1 and Week 2 of the 2-week Run-in Period
Convergent Validity for the SOBDA Questionnaire Measured as Correlations of the Baseline SOBDA Score With Participant-completed Modified Medical Research Council (mMRC) and Physician-completed mMRC Scores at Visit 2
Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the participant/physician-completed mMRC Dyspnea Scale assessments. The physician/participant rated the degree of the participant's dyspnea (trouble breathing) on the 5-point mMRC scale (0, none; 4, very severe). Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other.
Measured: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Convergent Validity for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Clinician Global Assessment of Dyspnea Severity (CGI-S) Score at Visit 2
Convergent validity is defined as the ability of the SOBDA questionnaire to measure the required information and was assessed by examining the relationship between the SOBDA score with the CGI-S score. Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe).
Measured: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Convergent Validity (CV) for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) Dyspnea Domain Score at Visit 2
Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the CRQ-SAS dyspnea domain score. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 will occur if the data from the 2 variables lie exactly on a line. The CRQ is a 20-item instrument measuring 4 domains (each measured on a scale of 1 [maximum impairment] to 7 [no impairment]) of functioning: mastery, fatigue, emotional function, and dyspnea.
Measured: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2
SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the PyC mMRC. The physician rated the degree of the participant's dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of PyC mMRC, both indicating increased levels of breathlessness.
Measured: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2
SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the ParC mMRC. The participant rated the degree of his/her dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of ParC mMRC, both indicating increased levels of breathlessness.
Measured: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2
SOBDA KGV refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the CGI-S score. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe). KGV was confirmed if the SOBDA score increased with increasing values of CGI-S, both indicating increased levels of breathlessness.
Measured: Baseline (last week of the 2-week Run-in Period) and pre-treatement on Visit 2 (Day 1 of the 6-week Treatment Period)
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD)
The PGAC is par. completed on a 1-5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Responders were defined as par. with a rating of "better" or "much better" (score of 4 or 5) on the PGAC at the relevant week; non-responders were defined as par. with a response of "much worse," "worse," or "no change" on the PGAC. As pre-specified in the study protocol, results are presented independent of treatment allocation . The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.
Measured: Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD)
Responsiveness reflects the ability of the SOBDA questionnaire to detect change under conditions of known change. Responders (Rs)=participants (par.) with a rating of "better"/"much better" (score of 4/5) on the PGAC (range; 1 [much worse] to 5 [much better]) at the relevant week; NRs=par. with a response of "much worse," "worse," or "no change" (score of 3). Mean difference between Rs and NRs in the change from the previous week to the current week's SOBDA score was calculated. For Visit 3/PD, the change from Baseline to the last treatment week's SOBDA score for Rs and NRs was calculated.
Measured: Baseline; Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Number of Participants Classified as Responders and Non-responders by Clinician Global Impression of Change Question (CGI-C) Response at Visit 3/PD
Clinicians were asked to provide their clinical impression regarding change in the participant's shortness of breath by CGI-C. This was evaluated on a 1-5 Likert scale: 1 (much worse) to 5 (much better), with 3 being no change. A CGI-C responder was defined as a participant who had a response of "better" (4) or "much better" (5), and a non-responder was defined as a participant who had a response of "much worse" (1), "worse" (2), or "no change" (3).
Measured: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Number of Participants Classified as Responders and Non-responders by CRQ-SAS Dyspnea Domain Response at Visit 3/PD
A CRQ-SAS dyspnea domain responder was defined as a participant who had a score increase of 0.5 units or more for the dyspnea domain of the CRQ-SAS between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had a decrease in the score, or an increase of less than 0.5 units.
Measured: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD
A Physician-completed and Participant-completed mMRC responder was defined as a participant who had a score decrease of one unit or more between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had the same score or an increase in score.
Measured: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Change From Baseline to Last Treatment Week in the SOBDA Score by CGI-C Responses at Visit 3/PD
The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the CGI-C conducted at Visit 3/Premature Discontinuation were assessed.
Measured: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Change From Baseline to Last Treatment Week in the SOBDA Score by CRQ-SAS Dyspnea Domain (DD) Responses at Visit 3/PD
The responsiveness of the SOBDA questionnaire was assessed by comparing score changes of responders (Rs) versus non-responders (NRs). The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing). Changes in mean SOBDA scores during the last treatment week in Rs and NRs using definitions based on the CRQ-SAS DD conducted at Visit 3/PD were assessed.
Measured: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD
The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The mMRC ranges from 0 (no breathlessness except with strenous exercise) to 4 (too breathless to leave the house; breathless when dressing/undressing) and is completed by the clinician or the participant as indicated. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the Physician-completed (Ph-C) and Participant-completed (Pa-C) mMRC conducted at Visit 3/Premature Discontinuation were assessed.
Measured: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better"
Changes from Baseline in the SOBDA score for responders (Rs) and non-responders (NRs) (using the PGAC assessment; 1 [much worse] to 5 [much better]), together with the cumulative proportions of Rs and NRs, was used to establish the threshold for defining SOBDA questionnaire Rs. The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on PGAC scores pre-specified as "better" or demonstrating meaningful improvement.
Measured: Baseline (last week of the 2-week Run-in Period) and Weeks 1, 2, 3, 4, 5, and 6 (6-week Treatment Period)
SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CGI-C Response Rated as "Better"
The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on CGI-C scores pre-specified as "better" or demonstrating meaningful improvement. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse, 2, worse; 3, no change; 4, better; 5, much better.
Measured: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CRQ-SAS Dyspnea Domain (DD) Response Rated as "Better"
The threshold of response (TOR) is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit. The TOR was evaluated as the change from Baseline in the SOBDA score based on CRQ-SAS scores pre-specified as "better" or demonstrating meaningful improvement. The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing).
Measured: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
SOBDA Threshold for Response Assessed as Mean Change From Baseline to Last Treatment Week in the SOBDA Score Based on Forced Expiratory Volume in One Second (FEV1) Change From Baseline of 50 Milliliters (mL) to <100 mL
FEV1 response was rated as 1=No change or worse (i.e., change of <50 mL); 2=Better (i.e., change of 50 to <100 mL); 3=Much better (i.e., change of >=100 mL). The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on study assessment (FEV1) scores pre-specified as "better" or demonstrating meaningful improvement.
Measured: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2009 (estimated)
- Study start29 Oct 2009
- Primary completion1 Jul 2010
- Study completion1 Jul 2010
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 (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 366 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984659
- Sponsor's protocol ID
- 112989
- Status last verified
- Aug 2018
- First submitted
- 24 Sep 2009
- Last updated
- 29 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Watkins ML, Wilcox TK, Tabberer M, Brooks JM, Donohue JF, Anzueto A, Chen WH, Crim C. Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease. BMJ Open. 2013 Oct 22;3(10):e003048. doi: 10.1136/bmjopen-2013-003048.
PubMed 24154513
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT00984659
- Acronym / sponsor ID
- 112989
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Pulmonary Disease, Chronic Obstructive, Dyspnea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 366 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 29 Oct 2009
- Primary completion
- 1 Jul 2010 (actual)
- Study completion
- 1 Jul 2010 (actual)
- First posted
- 25 Sep 2009 (estimated)
- Results
- Posted 15 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate a new questionnaire to capture the patient experience of COPD. The information collected will be used to validate the Shortness of Breath with Daily Activities Questionnaire.
Detailed description
Dyspnea, referred to by patients as "shortness of breath" or "breathlessness," is frequently associated with decreases in functional status, quality of life, and disabilities. Currently available questionnaires do not specifically address the shortness of breath component of COPD. The development of a patient reported outcome questionnaire that will specifically assess Shortness of Breath with Daily Activities (SOBDA) in patients with COPD is needed.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| FSC | Experimental | Drug: Fluticasone propionate/salmeterol combination productFluticasone propionate/salmeterol combination product 250/50mcg DISKUS twice a day |
| SAL | Experimental | Drug: SalmeterolSalmeterol 50mcg DISKUS twice a day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo DISKUS twice a day |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults ≥ 40 years of age
- Established clinical history of COPD by ATS/ERS definition
- Former or current smoker > 10 pack years
- Evidence of dyspnea
Key exclusion criteria (3 listed)
- Has a respiratory disorder other than COPD
- Cancer not in complete clinical remission
- Clinically significant cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine, or hematological abnormalities that are uncontrolled
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 |
|---|---|---|
| Fluticasone propionate/salmeterol combination productFluticasone propionate/salmeterol combination product 250/50mcg DISKUS twice a day for 8 weeks | Drug | FSC |
| SalmeterolSalmeterol 50mcg DISKUS twice a day for 8 weeks | Drug | SAL |
| PlaceboPlacebo DISKUS twice a day for 8 weeks | Drug | Placebo |
Primary outcome
Internal Consistency (IC) of the Shortness of Breath With Daily Activities (SOBDA) Questionnaire in Participants With Chronic Obstructive Pulmonary Disease (COPD) Assessed as Cronbach's Alpha Value
Time frame: Day 1 of the 2-week Run-in Period
Cronbach's alpha (CA) is a measure of the IC of the 13-item SOBDA questionnaire (completed via electronic diary by a sample of participants). It is the ratio of the variance (var.) of the sum of the individual scores and the var. of the total score. The var. of the sum of a group of independent variables is the sum of their var.; thus, if the variables are positively correlated, the var. of the sum will be increased. If the items making up the score are identical and so perfectly correlated, CA=1. If the items are independent, CA=0. Higher scores indicate a more reliable (precise) instrument.
Test-retest Reliability (T-RR) of SOBDA Scores Measured as the Difference in the SOBDA Weekly Score Between Week 1 and Week 2 of the 2-week Run-in Period
Time frame: Week 1 and Week 2 of the 2-week Run-in Period
T-RR=stability during repeat measures over time in a stable population. SOBDA score was determined by the 13-item (it.) scoring algorithm, assigning a weekly mean score of 1-4 (higher scores=more severe breathlessness with daily activities) based on the mean of 7 days of data (or >=4 days). Daily total score is computed from the mean of the participant's (par.) scores on the 13 it. (>=7 it. must have non-missing responses). Only scores of stable par. (indicating no change [score=3] on the par.-completed Patient Global Assessment of Change [PGAC]; 1 [ much worse] to 5 [much better]) were used.
Convergent Validity for the SOBDA Questionnaire Measured as Correlations of the Baseline SOBDA Score With Participant-completed Modified Medical Research Council (mMRC) and Physician-completed mMRC Scores at Visit 2
Time frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the participant/physician-completed mMRC Dyspnea Scale assessments. The physician/participant rated the degree of the participant's dyspnea (trouble breathing) on the 5-point mMRC scale (0, none; 4, very severe). Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other.
Convergent Validity for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Clinician Global Assessment of Dyspnea Severity (CGI-S) Score at Visit 2
Time frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Convergent validity is defined as the ability of the SOBDA questionnaire to measure the required information and was assessed by examining the relationship between the SOBDA score with the CGI-S score. Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe).
Convergent Validity (CV) for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) Dyspnea Domain Score at Visit 2
Time frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the CRQ-SAS dyspnea domain score. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 will occur if the data from the 2 variables lie exactly on a line. The CRQ is a 20-item instrument measuring 4 domains (each measured on a scale of 1 [maximum impairment] to 7 [no impairment]) of functioning: mastery, fatigue, emotional function, and dyspnea.
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2
Time frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the PyC mMRC. The physician rated the degree of the participant's dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of PyC mMRC, both indicating increased levels of breathlessness.
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2
Time frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)
SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the ParC mMRC. The participant rated the degree of his/her dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of ParC mMRC, both indicating increased levels of breathlessness.
Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2
Time frame: Baseline (last week of the 2-week Run-in Period) and pre-treatement on Visit 2 (Day 1 of the 6-week Treatment Period)
SOBDA KGV refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the CGI-S score. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe). KGV was confirmed if the SOBDA score increased with increasing values of CGI-S, both indicating increased levels of breathlessness.
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD)
Time frame: Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
The PGAC is par. completed on a 1-5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Responders were defined as par. with a rating of "better" or "much better" (score of 4 or 5) on the PGAC at the relevant week; non-responders were defined as par. with a response of "much worse," "worse," or "no change" on the PGAC. As pre-specified in the study protocol, results are presented independent of treatment allocation . The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD)
Time frame: Baseline; Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Responsiveness reflects the ability of the SOBDA questionnaire to detect change under conditions of known change. Responders (Rs)=participants (par.) with a rating of "better"/"much better" (score of 4/5) on the PGAC (range; 1 [much worse] to 5 [much better]) at the relevant week; NRs=par. with a response of "much worse," "worse," or "no change" (score of 3). Mean difference between Rs and NRs in the change from the previous week to the current week's SOBDA score was calculated. For Visit 3/PD, the change from Baseline to the last treatment week's SOBDA score for Rs and NRs was calculated.
Number of Participants Classified as Responders and Non-responders by Clinician Global Impression of Change Question (CGI-C) Response at Visit 3/PD
Time frame: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
Clinicians were asked to provide their clinical impression regarding change in the participant's shortness of breath by CGI-C. This was evaluated on a 1-5 Likert scale: 1 (much worse) to 5 (much better), with 3 being no change. A CGI-C responder was defined as a participant who had a response of "better" (4) or "much better" (5), and a non-responder was defined as a participant who had a response of "much worse" (1), "worse" (2), or "no change" (3).
Number of Participants Classified as Responders and Non-responders by CRQ-SAS Dyspnea Domain Response at Visit 3/PD
Time frame: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
A CRQ-SAS dyspnea domain responder was defined as a participant who had a score increase of 0.5 units or more for the dyspnea domain of the CRQ-SAS between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had a decrease in the score, or an increase of less than 0.5 units.
Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD
Time frame: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
A Physician-completed and Participant-completed mMRC responder was defined as a participant who had a score decrease of one unit or more between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had the same score or an increase in score.
Change From Baseline to Last Treatment Week in the SOBDA Score by CGI-C Responses at Visit 3/PD
Time frame: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the CGI-C conducted at Visit 3/Premature Discontinuation were assessed.
Change From Baseline to Last Treatment Week in the SOBDA Score by CRQ-SAS Dyspnea Domain (DD) Responses at Visit 3/PD
Time frame: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
The responsiveness of the SOBDA questionnaire was assessed by comparing score changes of responders (Rs) versus non-responders (NRs). The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing). Changes in mean SOBDA scores during the last treatment week in Rs and NRs using definitions based on the CRQ-SAS DD conducted at Visit 3/PD were assessed.
Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD
Time frame: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The mMRC ranges from 0 (no breathlessness except with strenous exercise) to 4 (too breathless to leave the house; breathless when dressing/undressing) and is completed by the clinician or the participant as indicated. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the Physician-completed (Ph-C) and Participant-completed (Pa-C) mMRC conducted at Visit 3/Premature Discontinuation were assessed.
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better"
Time frame: Baseline (last week of the 2-week Run-in Period) and Weeks 1, 2, 3, 4, 5, and 6 (6-week Treatment Period)
Changes from Baseline in the SOBDA score for responders (Rs) and non-responders (NRs) (using the PGAC assessment; 1 [much worse] to 5 [much better]), together with the cumulative proportions of Rs and NRs, was used to establish the threshold for defining SOBDA questionnaire Rs. The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on PGAC scores pre-specified as "better" or demonstrating meaningful improvement.
SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CGI-C Response Rated as "Better"
Time frame: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on CGI-C scores pre-specified as "better" or demonstrating meaningful improvement. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse, 2, worse; 3, no change; 4, better; 5, much better.
SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CRQ-SAS Dyspnea Domain (DD) Response Rated as "Better"
Time frame: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
The threshold of response (TOR) is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit. The TOR was evaluated as the change from Baseline in the SOBDA score based on CRQ-SAS scores pre-specified as "better" or demonstrating meaningful improvement. The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing).
SOBDA Threshold for Response Assessed as Mean Change From Baseline to Last Treatment Week in the SOBDA Score Based on Forced Expiratory Volume in One Second (FEV1) Change From Baseline of 50 Milliliters (mL) to <100 mL
Time frame: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)
FEV1 response was rated as 1=No change or worse (i.e., change of <50 mL); 2=Better (i.e., change of 50 to <100 mL); 3=Much better (i.e., change of >=100 mL). The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on study assessment (FEV1) scores pre-specified as "better" or demonstrating meaningful improvement.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24154513Watkins ML, Wilcox TK, Tabberer M, Brooks JM, Donohue JF, Anzueto A, Chen WH, Crim C. Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease. BMJ Open. 2013 Oct 22;3(10):e003048. doi: 10.1136/bmjopen-2013-003048.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
39 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluticasone propionate/salmeterol combination product and Salmeterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 39 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 4 inclusion and 3 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: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Mar 2012). 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?
Internal Consistency (IC) of the Shortness of Breath With Daily Activities (SOBDA) Questionnaire in Participants With Chronic Obstructive Pulmonary Disease (COPD) Assessed as Cronbach's Alpha Value (time frame: Day 1 of the 2-week Run-in Period). The study lists 20 primary outcomes in all. 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 NCT00984659, which also lists 1 linked publication.
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 29 Aug 2018.