Emphysema
Conditions
Keywords
COPD, emphysema, HRCT, losartan
Brief summary
A randomized, parallel, placebo controlled trial to evaluate the effect of 100mg/day losartan on the progression of emphysema as measured by quantitative HRCT compared to placebo .
Detailed description
This is a trial designed to test if a treatment, losartan, may decrease the progression of Chronic Obstructive Pulmonary Disease (COPD). Losartan is an angiotensin receptor blocking agent, commonly used as an antihypertensive agent, which has been shown to alter cardiac remodeling after myocardial infarction and renovascular remodeling in diabetes-mellitus. In this trial participants with mild to severe COPD, with Computed Tomography (CT) evidence of emphysema (5-35% of voxels with \< -950 Hounsfield Units), will be randomly assigned to receive 100mg/day of losartan or placebo for 48 weeks. The primary outcome measure will be the rate of progression of emphysema, quantified as the percent of lung voxels with a density less than -950 HU as measured by High Resolution CT (HRCT, from baseline to 48 weeks.
Interventions
DRUGLosartan
50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
DRUGPlacebo
one capsule per day for two weeks, followed by two capsules per day for 46 weeks
Sponsors
University of Pittsburgh
JHSPH Center for Clinical Trials
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mild to severe COPD: Ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than or equal to 0.70, FEV1 20-80% of predicted * Current or former smoker * HRCT scan with 5-35% of voxels with density less than -950 Hounsfield Units (HU) * Ability to understand and willingness to sign consent documents
Exclusion criteria
* Current therapy with angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) * Known intolerance to ACE inhibitor or ARB * History of angioedema * Conventional indication for ACE inhibitor or ARB (e.g., history of myocardial infarction, known cardiomyopathy) * Renal insufficiency (GFR \<30 mL/min by Cockcroft-Gault calculation) * Current regular use of NSAIDs defined as daily use 5 or more days of the week for more than one month * Potassium supplementation or serum potassium level of 5.0 milliequivalents (mEq)/dL or higher at V1 * Current use of a potassium sparing diuretic * COPD exacerbation requiring treatment within 6 weeks at V1 * Chronic systemic corticosteroid use of more than 10mg/day of prednisone * Resting SpO2 \<89% on 2 L nasal cannula continuous flow; unless at altitude \> 4,000 feet, then resting oxygen saturation (SpO2) \<89% on 4 L N C continuous flow * Untreated arterial hypertension (systolic blood pressure greater than140 mm Hg, diastolic blood pressure greater than 90 mm Hg) * Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic while standing or sitting * Known unilateral or bilateral renal artery stenosis higher than 70% * Previous lung resection surgery * Evidence of interstitial, occupational or chronic infectious lung disease * Changes to chest that preclude adequate HRCT imaging (e.g. Metallic objects in the chest such as shrapnel or pacemaker leads) * For women of child bearing potential, positive pregnancy test or unwillingness to use two methods of birth control or abstinence for the duration of the study * Major chronic illnesses which in the judgment of the study physician would interfere with participation in the study e.g. including but not limited to: cardiac, renal, hepatic (LFTs more than 2.5x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases, uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, non-skin cancer, rheumatic diseases * Failure to keep screening appointments or other indicators of non-adherence * Inability to be contacted by telephone * Intention to leave area within 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean pct950 | 48 weeks | change in percentage of voxels with density less than -950 Hounsfield Units |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Post-bronchodilator FEV1 Percent Predicted | 48 weeks | Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). This test is performed after the participant is given bronchodilator medications. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value. |
| Change From Baseline in CAT Score | 48 weeks | Change from the first visit to the final visit in the participant's COPD Assessment Test (CAT) score. The CAT is an 8-item questionnaire assessing the impact of COPD on health status. CAT scores range from 0 to 40, with higher scores indicating a more severe impact of COPD on a patient's life. |
| Change From Baseline in SGRQ Score: Total | 48 weeks | Change from the first visit to the final visit in participants' score on the St George's Respiratory Questionnaire - COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations. |
| Change From Baseline in SGRQ Score: Symptoms | 48 weeks | Change from the first visit to the final visit in participants' scores on the symptom-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations. |
| Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted | 48 weeks | Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). The test is administered without the participant taking any bronchodilator medication. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value. |
| Change in SGRQ Score: Impact | 48 weeks | Change from the first visit to the final visit in participants' scores on the impact-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations. |
| Change From Baseline in mMRC Dyspnea Scale | 48 weeks | Change from the first visit to the final visit in participants' scores on the modified Medical Research Council dyspnea scale. The modified Medical Research Council dyspnea scale (mMRC) is a self-rating tool to measure how much breathlessness affects someone's day to day activities. Scores are between 0 and 4, with higher scores indicating more severe breathlessness. |
| Change From Baseline in PROMIS-20a T-score | 48 weeks | Change from the first visit to the final visit in participants' scores on the Patient-Reported Outcome Measures Information System (PROMIS) Physical Function assessment. The Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 20a is a 20-item questionnaire used to indicate a patient's ability to perform activities of daily living, such as bathing, dressing, and commuting. Raw scores from this questionnaire are compared to a reference population to create a T-score. The general US population is the reference population. In this T-score metric, 50 indicates the population mean with a standard deviation of 10. Higher scores mean better outcomes (more ability to do activities of daily living) |
| Change From Baseline in SGRQ Score: Activity | 48 weeks | Change from the first visit to the final visit in participants' scores on the activity-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations. |
Countries
United States
Participant flow
Recruitment details
2,779 individuals were screened for this study; of those, 2,028 were determined to be ineligible, and 531 declined to participate.
Pre-assignment details
220 individuals were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Losartan At randomization participants will start with a dose of 50mg (one capsule) once a day for 2 weeks. If this dose is well tolerated and systolic BP is \>90 mm Hg and diastolic BP is \> 60 mm Hg, the dose will be increased to 100 mg (2 capsules) once a day for the remaining 46 weeks.
Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated | 108 |
| Placebo At randomization participants will start with a dose of one capsule (inactive) once a day for 2 weeks. After two weeks, if systolic BP is \>90 mm Hg and diastolic BP is \> 60 mm Hg, the dose will be increased to 2 capsules once a day for the remaining 46 weeks.
Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks | 112 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Baseline and final high-resolution computed tomography (HRCT) scans conducted on different scanners | 2 | 2 |
| Overall Study | Death | 1 | 2 |
| Overall Study | High-resolution computed tomography (HRCT) scan conducted on unknown scanner | 1 | 1 |
| Overall Study | Incorrect kernel used in high-resolution computed tomography (HRCT) scan | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Missed final HRCT scan due to coronavirus disease pandemic | 3 | 1 |
| Overall Study | Participant diagnosed with lung cancer | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Losartan | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 66 years | 65 years | 65 years |
| Body Mass Index (BMI) | 27 kg/m^2 | 26 kg/m^2 | 26 kg/m^2 |
| COPD Assessment Test | 17 units on a scale | 17 units on a scale | 16 units on a scale |
| COPD Assessment Test impact level Mild | 21 Participants | 47 Participants | 26 Participants |
| COPD Assessment Test impact level Moderate | 52 Participants | 97 Participants | 45 Participants |
| COPD Assessment Test impact level Severe | 35 Participants | 68 Participants | 33 Participants |
| COPD Assessment Test impact level Very severe | 0 Participants | 8 Participants | 8 Participants |
| Current smokers (past month) | 26 Participants | 52 Participants | 26 Participants |
| Modified Medical Research Council dyspnea scale | 1 units on a scale | 1 units on a scale | 1 units on a scale |
| PROMIS Physical Function-20a | 40 units on a scale | 40 units on a scale | 40 units on a scale |
| Race/Ethnicity, Customized Black or African American | 19 Participants | 42 Participants | 23 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 88 Participants | 176 Participants | 88 Participants |
| Region of Enrollment United States | 108 participants | 220 participants | 112 participants |
| Sex: Female, Male Female | 47 Participants | 93 Participants | 46 Participants |
| Sex: Female, Male Male | 61 Participants | 127 Participants | 66 Participants |
| Sitting Blood Pressure Diastolic | 77 Millimeters of mercury (mmHg) | 76 Millimeters of mercury (mmHg) | 75 Millimeters of mercury (mmHg) |
| Sitting Blood Pressure Systolic | 125 Millimeters of mercury (mmHg) | 124 Millimeters of mercury (mmHg) | 123 Millimeters of mercury (mmHg) |
| Smoking history | 46 Pack-years | 44 Pack-years | 42 Pack-years |
| Spirometry percent predicted Post-bronchodilator % predicted FEV1 | 48 Percent predicted | 48 Percent predicted | 48 Percent predicted |
| Spirometry percent predicted Pre-bronchodilator % predicted FEV1 | 43 Percent predicted | 43 Percent predicted | 43 Percent predicted |
| Spirometry pre-bronchodilator FEV1 | 1.1 Liters | 1.1 Liters | 1.1 Liters |
| St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD) score Activity | 59 units on a scale | 59 units on a scale | 59 units on a scale |
| St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD) score Impact | 28 units on a scale | 27 units on a scale | 26 units on a scale |
| St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD) score Symptoms | 55 units on a scale | 55 units on a scale | 56 units on a scale |
| St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD) score Total | 42 units on a scale | 42 units on a scale | 40 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 108 | 2 / 112 |
| other Total, other adverse events | 106 / 108 | 112 / 112 |
| serious Total, serious adverse events | 18 / 108 | 25 / 112 |
Outcome results
Primary
Change in Mean pct950
change in percentage of voxels with density less than -950 Hounsfield Units
Time frame: 48 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change in Mean pct950 | 1.35 percentage of voxels |
| Placebo | Change in Mean pct950 | 0.66 percentage of voxels |
p-value: 0.133Mixed Models Analysis
Secondary
Change From Baseline in CAT Score
Change from the first visit to the final visit in the participant's COPD Assessment Test (CAT) score. The CAT is an 8-item questionnaire assessing the impact of COPD on health status. CAT scores range from 0 to 40, with higher scores indicating a more severe impact of COPD on a patient's life.
Time frame: 48 weeks
Population: CAT results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 8 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in CAT Score | -0.18 score on a scale |
| Placebo | Change From Baseline in CAT Score | 0.03 score on a scale |
p-value: 0.783Mixed Models Analysis
Secondary
Change From Baseline in mMRC Dyspnea Scale
Change from the first visit to the final visit in participants' scores on the modified Medical Research Council dyspnea scale. The modified Medical Research Council dyspnea scale (mMRC) is a self-rating tool to measure how much breathlessness affects someone's day to day activities. Scores are between 0 and 4, with higher scores indicating more severe breathlessness.
Time frame: 48 weeks
Population: mMRC dyspnea scale results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in mMRC Dyspnea Scale | 0.01 score on a scale |
| Placebo | Change From Baseline in mMRC Dyspnea Scale | 0.11 score on a scale |
p-value: 0.356Mixed Models Analysis
Secondary
Change From Baseline in Post-bronchodilator FEV1 Percent Predicted
Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). This test is performed after the participant is given bronchodilator medications. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value.
Time frame: 48 weeks
Population: Post-bronchodilator results were not available at the baseline and/or final visit for 35 participants in the Losartan group and 39 participants in the placebo group. This was due in part to the elimination of all non-medically necessary spirometry testing during the COVID-19 pandemic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in Post-bronchodilator FEV1 Percent Predicted | -2.60 percentage of predicted value |
| Placebo | Change From Baseline in Post-bronchodilator FEV1 Percent Predicted | -2.37 percentage of predicted value |
p-value: 0.834Mixed Models Analysis
Secondary
Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted
Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). The test is administered without the participant taking any bronchodilator medication. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value.
Time frame: 48 weeks
Population: Pre-bronchodilator results were not available at the baseline and/or final visit for 57 participants in the Losartan group and 56 participants in the placebo group. This was due in part to the elimination of all non-medically necessary spirometry testing during the COVID-19 pandemic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted | -0.99 percentage of predicted value |
| Placebo | Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted | -0.54 percentage of predicted value |
p-value: 0.762Mixed Models Analysis
Secondary
Change From Baseline in PROMIS-20a T-score
Change from the first visit to the final visit in participants' scores on the Patient-Reported Outcome Measures Information System (PROMIS) Physical Function assessment. The Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 20a is a 20-item questionnaire used to indicate a patient's ability to perform activities of daily living, such as bathing, dressing, and commuting. Raw scores from this questionnaire are compared to a reference population to create a T-score. The general US population is the reference population. In this T-score metric, 50 indicates the population mean with a standard deviation of 10. Higher scores mean better outcomes (more ability to do activities of daily living)
Time frame: 48 weeks
Population: PROMIS-20a results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 10 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in PROMIS-20a T-score | 0.00 score on a scale |
| Placebo | Change From Baseline in PROMIS-20a T-score | -1.04 score on a scale |
p-value: 0.009Mixed Models Analysis
Secondary
Change From Baseline in SGRQ Score: Activity
Change from the first visit to the final visit in participants' scores on the activity-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Time frame: 48 weeks
Population: SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in SGRQ Score: Activity | -0.66 score on a scale |
| Placebo | Change From Baseline in SGRQ Score: Activity | 2.45 score on a scale |
p-value: 0.065Mixed Models Analysis
Secondary
Change From Baseline in SGRQ Score: Symptoms
Change from the first visit to the final visit in participants' scores on the symptom-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Time frame: 48 weeks
Population: SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in SGRQ Score: Symptoms | -6.19 score on a scale |
| Placebo | Change From Baseline in SGRQ Score: Symptoms | -1.78 score on a scale |
p-value: 0.016Mixed Models Analysis
Secondary
Change From Baseline in SGRQ Score: Total
Change from the first visit to the final visit in participants' score on the St George's Respiratory Questionnaire - COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Time frame: 48 weeks
Population: Total SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change From Baseline in SGRQ Score: Total | -1.31 score on a scale |
| Placebo | Change From Baseline in SGRQ Score: Total | 1.20 score on a scale |
p-value: 0.053Mixed Models Analysis
Secondary
Change in SGRQ Score: Impact
Change from the first visit to the final visit in participants' scores on the impact-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Time frame: 48 weeks
Population: SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Losartan | Change in SGRQ Score: Impact | -0.25 score on a scale |
| Placebo | Change in SGRQ Score: Impact | 1.35 score on a scale |
p-value: 0.293Mixed Models Analysis
Post Hoc
Number of COPD Exacerbations by Severity and Treatment Assignment
This measure assessed the number of exacerbations of chronic obstructive pulmonary disease in both the losartan and placebo treatment groups. Participants were asked about current and past exacerbations during each study visit. Exacerbations were defined as 2 or more worsening COPD symptoms lasting 3 or more consecutive days that required a new prescribed treatment. Each exacerbation was further classified as mild (requiring only a change in existing COPD medications),moderate (requiring a new prescription for a steroid and/or antibiotic), or severe (requiring a hospitalization for COPD symptoms).
Time frame: 48 weeks
Population: The analysis population consists of the number of participants who reported at least one exacerbation in each treatment group. Two participants in the losartan treatment group did not report any COPD exacerbations during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan | Number of COPD Exacerbations by Severity and Treatment Assignment | Mild exacerbation | 3 exacerbation events |
| Losartan | Number of COPD Exacerbations by Severity and Treatment Assignment | Moderate exacerbation | 41 exacerbation events |
| Losartan | Number of COPD Exacerbations by Severity and Treatment Assignment | Severe exacerbation | 7 exacerbation events |
| Placebo | Number of COPD Exacerbations by Severity and Treatment Assignment | Mild exacerbation | 4 exacerbation events |
| Placebo | Number of COPD Exacerbations by Severity and Treatment Assignment | Moderate exacerbation | 47 exacerbation events |
| Placebo | Number of COPD Exacerbations by Severity and Treatment Assignment | Severe exacerbation | 21 exacerbation events |
Comparison: P-value for rate of mild exacerbations between treatment groups (measured in events per 100 person-years).p-value: 0.89295% CI: [0.03, 18.77]Negative binomial model
Comparison: P-value for rate of moderate exacerbations between treatment groups (measured in events per 100 person-years).p-value: 0.94695% CI: [0.05, 14.97]Negative binomial model
Comparison: P-value for rate of severe exacerbations between treatment groups (measured in events per 100 person-years).p-value: 0.48795% CI: [0.02, 6.51]Negative binomial model