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

• ClinicalTrials.gov Identifier: NCT00805025
• Recruitment Status: Completed
• First Posted: December 9, 2008
• Results First Posted: March 20, 2014
• Last Update Posted: March 20, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bronchiectasis
• Intervention: Drug: AZLI
• Enrollment: 89

Participant Flow

Recruitment Details	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.
Pre-assignment Details	131 participants were screened and 89 were enrolled and treated.

Arm/Group Title	AZLI
Arm/Group Description	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.
Period Title: Overall Study
Started	131
Enrolled and Treated	89
Completed	82
Not Completed	49
Reason Not Completed
Screened but not enrolled/treated	42
Adverse Event	4
Withdrawal by Subject	2
Physician Decision	1

Baseline Characteristics

Arm/Group Title		AZLI
Arm/Group Description		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.
Overall Number of Baseline Participants		89
Baseline Analysis Population Description		Enrolled and treated participants
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	89 participants
		64 (14.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	89 participants
	Female	62 69.7%
	Male	27 30.3%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	89 participants
Asian		2
African-American		3
White		84

Outcome Measures

1. Primary Outcome

Title	Reliability of the Respiratory Domain of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)
Description	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.
Time Frame	Day -14 to Day 0

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AZLI
Arm/Group Description:	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.
Overall Number of Participants Analyzed	86
Measure Type: Number; Unit of Measure: Intraclass Correlation Coefficient
	0.80

2. Primary Outcome

Title	Convergent Validity of the Respiratory Domain of the QOL-B
Description	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.
Time Frame	Day -14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZLI
Arm/Group Description:	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.
Overall Number of Participants Analyzed	131
Measure Type: Number; Unit of Measure: Pearson correlation coefficient
HRCT overall sentisitivity (n = 118)	-0.19
FEV1 % predicted (n = 119)	0.11
6MWT (n = 121)	0.16
SGRQ symptoms (n = 121)	-0.75

3. Secondary Outcome

Title	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)
Description	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.
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZLI
Arm/Group Description:	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.
Overall Number of Participants Analyzed	83
Mean (Standard Deviation); Unit of Measure: units on a scale
	2.9 (10.2)

Adverse Events

Time Frame	Pre-baseline through 70 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	AZLI
Arm/Group Description	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.
All-Cause Mortality
	AZLI
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	AZLI
	Affected / at Risk (%)
Total	4/89 (4.49%)
Injury, poisoning and procedural complications
Pelvic fracture † 1	1/89 (1.12%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/89 (1.12%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis † 1	1/89 (1.12%)
Chronic obstructive pulmonary disease † 1	1/89 (1.12%)
Lung disorder † 1	1/89 (1.12%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (11.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	AZLI
	Affected / at Risk (%)
Total	36/89 (40.45%)
Gastrointestinal disorders
Diarrhoea † 1	8/89 (8.99%)
General disorders
Pyrexia † 1	7/89 (7.87%)
Fatigue † 1	6/89 (6.74%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	10/89 (11.24%)
Dyspnoea † 1	9/89 (10.11%)
Productive cough † 1	8/89 (8.99%)
Wheezing † 1	8/89 (8.99%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (11.1)

Limitations and Caveats

[Not Specified]

More Information

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.

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

Results Point of Contact

• Name/Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.
• EMail: ClinicalTrialDisclosures@gilead.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Quittner AL, Marciel KK, Salathe MA, O'Donnell AE, Gotfried MH, Ilowite JS, Metersky ML, Flume PA, Lewis SA, McKevitt M, Montgomery AB, O'Riordan TG, Barker AF. A preliminary quality of life questionnaire-bronchiectasis: a patient-reported outcome measure for bronchiectasis. Chest. 2014 Aug;146(2):437-448. doi: 10.1378/chest.13-1891. Review. Erratum in: Chest. 2014 Nov;146(5):1422.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00805025
• Other Study ID Numbers: GS-US-219-0102
• First Submitted: December 5, 2008
• First Posted: December 9, 2008
• Results First Submitted: September 9, 2013
• Results First Posted: March 20, 2014
• Last Update Posted: March 20, 2014