Trial Outcomes & Findings for Evaluation of the Quality of Life Questionnaire-Bronchiectasis (QOL-B) in Patients With Bronchiectasis (NCT NCT00805025)

Results Overview

Test-retest reliability is a measure of the stability or reproducibility of a measure over a period of time during which status on the underlying construct has not changed, and is measured by the intraclass correlation of scores obtained at 2 time points within that period. Test-retest reliability of respiratory symptoms was calculated for response at Day -14 and Day 0. Reliability of the participants' QOL-B responses was assessed from an Intraclass Correlation Coefficient (ICC). A score of ≥ 0.70 would indicate strong reliability. The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

89 participants

Primary outcome timeframe

Day -14 to Day 0

Results posted on

2014-03-20

Participant Flow

Participants were enrolled at a total of 21 study sites in the United States. The first participant was screened on 08 December 2008. The last participant observation was on 14 October 2009.

131 participants were screened and 89 were enrolled and treated.

Participant milestones

Participant milestones
Measure	AZLI Participants were evaluated beginning 14 days prior to starting a 28-day course of aztreonam for inhalation solution (AZLI) 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Overall Study STARTED	131
Overall Study Enrolled and Treated	89
Overall Study COMPLETED	82
Overall Study NOT COMPLETED	49

Reasons for withdrawal

Reasons for withdrawal
Measure	AZLI Participants were evaluated beginning 14 days prior to starting a 28-day course of aztreonam for inhalation solution (AZLI) 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Overall Study Screened but not enrolled/treated	42
Overall Study Adverse Event	4
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	1

Baseline Characteristics

Evaluation of the Quality of Life Questionnaire-Bronchiectasis (QOL-B) in Patients With Bronchiectasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZLI n=89 Participants Participants were evaluated beginning 14 days prior to starting a 28-day course of AZLI 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Age, Continuous	64 years STANDARD_DEVIATION 14.7 • n=93 Participants
Sex: Female, Male Female	62 Participants n=93 Participants
Sex: Female, Male Male	27 Participants n=93 Participants
Race/Ethnicity, Customized Asian	2 participants n=93 Participants
Race/Ethnicity, Customized African-American	3 participants n=93 Participants
Race/Ethnicity, Customized White	84 participants n=93 Participants

PRIMARY outcome

Timeframe: Day -14 to Day 0

Population: Participants who were treated and had any QOL-B measurements at both Screening and Day 0 (Visits 1 and 2) were analyzed.

Test-retest reliability is a measure of the stability or reproducibility of a measure over a period of time during which status on the underlying construct has not changed, and is measured by the intraclass correlation of scores obtained at 2 time points within that period. Test-retest reliability of respiratory symptoms was calculated for response at Day -14 and Day 0. Reliability of the participants' QOL-B responses was assessed from an Intraclass Correlation Coefficient (ICC). A score of ≥ 0.70 would indicate strong reliability. The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Outcome measures

Outcome measures
Measure	AZLI n=86 Participants Participants were evaluated beginning 14 days prior to starting a 28-day course of AZLI 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Reliability of the Respiratory Domain of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)	0.80 Intraclass Correlation Coefficient

PRIMARY outcome

Timeframe: Day -14

Population: Participants were analyzed for respiratory domain score at Day 0 against each of the other variables; those with data for both the respiratory domain score and each variable are reported.

Convergent validity was assessed at Day -14 by examining the correlations between relevant QOL-B domains and other indicators of health status: a bronchiectasis severity score based on high-resolution computerised tomography (HRCT) scan results, forced expiratory volume in 1 second (FEV1) percent predicted, 6-minute walk test (6MWT) results, and St. George's Respiratory Questionnaire (SGRQ) symptoms scores. Correlations with absolute values of 0.30 to 0.50 indicated moderate evidence of convergent validity.

Outcome measures

Outcome measures
Measure	AZLI n=131 Participants Participants were evaluated beginning 14 days prior to starting a 28-day course of AZLI 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Convergent Validity of the Respiratory Domain of the QOL-B HRCT overall sentisitivity (n = 118)	-0.19 Pearson correlation coefficient
Convergent Validity of the Respiratory Domain of the QOL-B FEV1 % predicted (n = 119)	0.11 Pearson correlation coefficient
Convergent Validity of the Respiratory Domain of the QOL-B 6MWT (n = 121)	0.16 Pearson correlation coefficient
Convergent Validity of the Respiratory Domain of the QOL-B SGRQ symptoms (n = 121)	-0.75 Pearson correlation coefficient

SECONDARY outcome

Timeframe: Day 0 to Day 28

Population: Participants who were evaluable for MCID and had both GRCQ and QOL-B change values at Day 28 (Visit 4) in any GRCQ domain were analyzed.

The anchor-based method measured the participant's perception of change at Day 28 using the GRCQ, which assesses improving/worsening symptoms. Distribution of ratings was categorized as no change (-1 to 1), minimal change (≥ 1.1 to \< 3.1 or ≤ -1.1 to \> -3.1), moderate change (≥ 3.1 to \< 5.1 or ≤ -3.1 to \> -5.1) or large change (≥ 5.1, ≤ -5.1). The GRCQ evaluated change in respiratory symptoms on a visual analog scale from -7 (worsening) to +7 (improvement). The following algorithm was used to obtain the mean change: If the corresponding GRCQ score was in the "no change" group, then change from baseline QOL-B = Observed QOL-B change from baseline score; if \> 1, then change from baseline QOL-B score = Observed QOL-B change from baseline score; if \< -1, the change from baseline QOL-B score = (-1) \* Observed QOL-B change from baseline score. Then the mean change from baseline of QOL-B respiratory symptoms score of the minimal change category group is the anchor-based MCID.

Outcome measures

Outcome measures
Measure	AZLI n=83 Participants Participants were evaluated beginning 14 days prior to starting a 28-day course of AZLI 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Responsiveness of the Respiratory Domain of the QOL-B as Assessed by the Anchor-based Minimal Clinically Important Difference (MCID) Following Categorization of Level of Change Using the Global Rating of Change Questionnaire (GRCQ)	2.9 units on a scale Standard Deviation 10.2

Adverse Events

AZLI

Serious events: 4 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZLI n=89 participants at risk Participants were evaluated beginning 14 days prior to starting a 28-day course of AZLI 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	1.1% 1/89 • Pre-baseline through 70 days
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.1% 1/89 • Pre-baseline through 70 days
Respiratory, thoracic and mediastinal disorders Lung disorder	1.1% 1/89 • Pre-baseline through 70 days
Injury, poisoning and procedural complications Pelvic fracture	1.1% 1/89 • Pre-baseline through 70 days
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/89 • Pre-baseline through 70 days

Other adverse events

Other adverse events
Measure	AZLI n=89 participants at risk Participants were evaluated beginning 14 days prior to starting a 28-day course of AZLI 75 mg three times daily via investigational nebulizer (Day 0 to Day 28), followed by post-treatment assessments every 14 days through Day 56, for a total of 70 days of participation in the study.
Respiratory, thoracic and mediastinal disorders Cough	11.2% 10/89 • Pre-baseline through 70 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.1% 9/89 • Pre-baseline through 70 days
Gastrointestinal disorders Diarrhoea	9.0% 8/89 • Pre-baseline through 70 days
Respiratory, thoracic and mediastinal disorders Productive cough	9.0% 8/89 • Pre-baseline through 70 days
Respiratory, thoracic and mediastinal disorders Wheezing	9.0% 8/89 • Pre-baseline through 70 days
General disorders Pyrexia	7.9% 7/89 • Pre-baseline through 70 days
General disorders Fatigue	6.7% 6/89 • Pre-baseline through 70 days

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER