Last reviewed · How we verify

NCT00984659

Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease

Completed Phase 4 Results posted Last updated 29 August 2018
What this trial tests

Phase 4 trial testing Fluticasone propionate/salmeterol combination product in Pulmonary Disease, Chronic Obstructive in 366 participants. Completed in 1 July 2010.

Timeline
29 October 2009
Primary endpoint
1 July 2010
1 July 2010

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposeother
Enrollment366
Start date29 October 2009
Primary completion1 July 2010
Estimated completion1 July 2010
Sites39 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

40 and older, any sex, with Pulmonary Disease, Chronic Obstructive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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.

GroupValue95% CI
All Participants: 2-week Run-in Period0.892
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 Primary · 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 \[much better\]) w

GroupValue95% CI
All Participants: 2-week Run-in Period0.01± 0.244
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 Primary · 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.

Physician-completed mMRC, n=339
GroupValue95% CI
All Participants: 2-week Run-in Period0.24
Participant-completed mMRC, n=340
GroupValue95% CI
All Participants: 2-week Run-in Period0.29
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 Primary · 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).

GroupValue95% CI
All Participants: 2-week Run-in Period0.24
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 Primary · 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.

GroupValue95% CI
All Participants: 2-week Run-in Period-0.68
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 Primary · 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.

PyC mMRC: 0 to 1, n=12
GroupValue95% CI
All Participants: 2-week Run-in Period1.78± 0.196
PyC mMRC: 2, n=200
GroupValue95% CI
All Participants: 2-week Run-in Period2.08± 0.048
PyC mMRC: 3, n=117
GroupValue95% CI
All Participants: 2-week Run-in Period2.28± 0.063
PyC mMRC: 4, n=10
GroupValue95% CI
All Participants: 2-week Run-in Period2.73± 0.216
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 Primary · 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.

ParC mMRC: 0, n=12
GroupValue95% CI
All Participants: 2-week Run-in Period1.92± 0.192
ParC mMRC: 1, n=103
GroupValue95% CI
All Participants: 2-week Run-in Period1.94± 0.066
ParC mMRC: 2, n=138
GroupValue95% CI
All Participants: 2-week Run-in Period2.20± 0.056
ParC mMRC: 3, n=65
GroupValue95% CI
All Participants: 2-week Run-in Period2.26± 0.083
ParC mMRC: 4, n=22
GroupValue95% CI
All Participants: 2-week Run-in Period2.73± 0.142
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 Primary · 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.

CGI-S: 1, n=19
GroupValue95% CI
All Participants: 2-week Run-in Period1.87± 0.156
CGI-S: 2, n=236
GroupValue95% CI
All Participants: 2-week Run-in Period2.11± 0.045
CGI-S: 3, n=78
GroupValue95% CI
All Participants: 2-week Run-in Period2.33± 0.080
CGI-S: 4, n=5
GroupValue95% CI
All Participants: 2-week Run-in Period2.72± 0.305
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) Primary · 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.

Responders, Day 8 (Baseline to Week 1), n=293
GroupValue95% CI
MITT Population: 6-Week Treatment Period105
Non-responders, Day 8 (Baseline to Week 1), n=293
GroupValue95% CI
MITT Population: 6-Week Treatment Period188
Responders, Day 15 (Week 1 to Week 2), n=303
GroupValue95% CI
MITT Population: 6-Week Treatment Period91
Non-responders, Day 15 (Week 1 to Week 2), n=303
GroupValue95% CI
MITT Population: 6-Week Treatment Period212
Responders, Day 22 (Week 2 to Week 3), n=299
GroupValue95% CI
MITT Population: 6-Week Treatment Period83
Non-responders, Day 22 (Week 2 to Week 3), n=299
GroupValue95% CI
MITT Population: 6-Week Treatment Period216
Responders, Day 29 (Week 3 to Week 4), n=285
GroupValue95% CI
MITT Population: 6-Week Treatment Period62
Non-responders, Day 29 (Week 3 to Week 4), n=285
GroupValue95% CI
MITT Population: 6-Week Treatment Period223
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) Primary · 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.

Baseline to Day 8, responders, n=105
GroupValue95% CI
MITT Population: 6-Week Treatment Period-0.26± 0.324
Baseline to Day 8, non-responders, n=188
GroupValue95% CI
MITT Population: 6-Week Treatment Period-0.01± 0.254
Day 8 to Day 15, responders, n=91
GroupValue95% CI
MITT Population: 6-Week Treatment Period-0.10± 0.280
Day 8 to Day 15, non-responders, n=212
GroupValue95% CI
MITT Population: 6-Week Treatment Period0.01± 0.222
Day 15 to Day 22, responders, n=83
GroupValue95% CI
MITT Population: 6-Week Treatment Period-0.08± 0.223
Day 15 to Day 22, non-responders, n=216
GroupValue95% CI
MITT Population: 6-Week Treatment Period0.02± 0.183
Day 22 to Day 29, responders, n=62
GroupValue95% CI
MITT Population: 6-Week Treatment Period-0.09± 0.198
Day 22 to Day 29, non-responders, n=223
GroupValue95% CI
MITT Population: 6-Week Treatment Period0.01± 0.193
Number of Participants Classified as Responders and Non-responders by Clinician Global Impression of Change Question (CGI-C) Response at Visit 3/PD Primary · 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).

Responders
GroupValue95% CI
MITT Population: 6-Week Treatment Period120
Non-responders
GroupValue95% CI
MITT Population: 6-Week Treatment Period181
Number of Participants Classified as Responders and Non-responders by CRQ-SAS Dyspnea Domain Response at Visit 3/PD Primary · 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.

Responders
GroupValue95% CI
MITT Population: 6-Week Treatment Period117
Non-responders
GroupValue95% CI
MITT Population: 6-Week Treatment Period184

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 4/75 (5%)
Deaths:
SAL 50 mcg
Serious: 5/151 (3%)
Deaths:
FSC 250/50 mcg
Serious: 3/139 (2%)
Deaths:

Serious adverse events (12 terms)

ReactionSystemPlaceboSAL 50 mcgFSC 250/50 mcg
Chronic Obstructive Pulmonary DiseaseRespiratory, thoracic and mediastinal disorders
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Myocardial InfarctionCardiac disorders
Impaired Gastric EmptyingGastrointestinal disorders
Chest PainGeneral disorders
PneumoniaInfections and infestations
DehydrationMetabolism and nutrition disorders
Diabetes Mellitus Inadequate ControlMetabolism and nutrition disorders
Cerebrovascular AccidentNervous system disorders
Suicide AttemptPsychiatric disorders
Other adverse events (93 terms — click to expand)

ReactionSystemPlaceboSAL 50 mcgFSC 250/50 mcg
HeadacheNervous system disorders
Chronic Obstructive Pulmonary DiseaseRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
CandidiasisInfections and infestations
Sinus HeadacheNervous system disorders
Chest PainGeneral disorders
Sinus CongestionRespiratory, thoracic and mediastinal disorders
Respiratory Tract CongestionRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
PneumoniaInfections and infestations
Respiratory Tract InfectionInfections and infestations
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Pain In ExtremityMusculoskeletal and connective tissue disorders
HyperlipidemiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Rhinitis AllergicRespiratory, thoracic and mediastinal disorders
RhinorrheaRespiratory, thoracic and mediastinal disorders
BronchitisInfections and infestations
Gastroenteritis ViralInfections and infestations
InfluenzaInfections and infestations
Acute SinusitisInfections and infestations
Gastric InfectionInfections and infestations
PharyngitisInfections and infestations
Pneumonia KlebsiellaInfections and infestations
SinusitisInfections and infestations
TracheobronchitisInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
Viral Upper Respiratory Tract InfectionInfections and infestations
Carpal tunnel SyndromeNervous system disorders
Cerebrovascular AccidentNervous system disorders

Most-reported serious reactions: Chronic Obstructive Pulmonary Disease, Acute Respiratory Failure, Pneumothorax, Respiratory Failure, Myocardial Infarction, Impaired Gastric Emptying, Chest Pain, Pneumonia.

Data from ClinicalTrials.gov NCT00984659 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease.
    Watkins ML, Wilcox TK, Tabberer M, Brooks JM, et al · · 2013 · cited 16× · PMID 24154513 · DOI 10.1136/bmjopen-2013-003048

Verify or expand the search:

Other recruiting trials for Pulmonary Disease, Chronic Obstructive

Currently open trials in the same condition.

Other GlaxoSmithKline trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00984659.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing