Bronchiectasis
Conditions
Brief summary
Over the 70-day study period, eligible patients visited the study clinic every 2 weeks (total of 6 visits) and received a 28-day course of aztreonam for inhalation solution (AZLI). The Quality of Life-Bronchiectasis (QOL-B) questionnaire was completed at several time points during the study, in additional to pulmonary function testing and other standard procedures.
Interventions
DRUGAZLI
75 mg aztreonam for inhalation solution (AZLI), administered 3 times daily using the PARI Investigational eFlow® Nebulizer System (with a minimum of 4 hours between doses) following administration of a short-acting bronchodilator
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent prior to any study-related procedures * Ability to read and understand the English language * Bronchiectasis confirmed by CT scan of the chest * Previous treatment with antibiotics for bronchiectasis * Documented history of positive sputum culture for a gram-negative organism within 5 years * Positive sputum culture for a gram-negative organism at first visit (Day -14)
Exclusion criteria
* Hospitalization or hemoptysis \> 30 mL within 14 days of first visit (Day -14) * Antibiotic use for respiratory symptoms within 14 days of first visit (Day -14), excluding chronic, stable azithromycin use * Change in corticosteroid or bronchodilator regimen within 14 days of first visit (Day -14) * Forced expiratory volume in 1 second (FEV1) \< 25% predicted approximately 15 minutes following use of a bronchodilator at first visit (Day -14) * Cigarette smoking within 6 months of first visit (Day -14)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reliability of the Respiratory Domain of the Quality of Life Questionnaire-Bronchiectasis (QOL-B) | Day -14 to Day 0 | 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. |
| Convergent Validity of the Respiratory Domain of the QOL-B | Day -14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day 0 to Day 28 | 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| AZLI 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. | 89 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Screened but not enrolled/treated | 42 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | AZLI |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 14.7 |
| Race/Ethnicity, Customized African-American | 3 participants |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized White | 84 participants |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 89 |
| serious Total, serious adverse events | 4 / 89 |
Outcome results
Primary
Convergent Validity of the Respiratory Domain of the QOL-B
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZLI | Convergent Validity of the Respiratory Domain of the QOL-B | 6MWT (n = 121) | 0.16 Pearson correlation coefficient |
| AZLI | Convergent Validity of the Respiratory Domain of the QOL-B | HRCT overall sentisitivity (n = 118) | -0.19 Pearson correlation coefficient |
| AZLI | Convergent Validity of the Respiratory Domain of the QOL-B | FEV1 % predicted (n = 119) | 0.11 Pearson correlation coefficient |
| AZLI | Convergent Validity of the Respiratory Domain of the QOL-B | SGRQ symptoms (n = 121) | -0.75 Pearson correlation coefficient |
Primary
Reliability of the Respiratory Domain of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)
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
Population: Participants who were treated and had any QOL-B measurements at both Screening and Day 0 (Visits 1 and 2) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZLI | Reliability of the Respiratory Domain of the Quality of Life Questionnaire-Bronchiectasis (QOL-B) | 0.80 Intraclass Correlation Coefficient |
Secondary
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)
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZLI | 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 |