Chronic Bronchitis, COPD, Emphysema, Smoking
Conditions
Keywords
COPD, emphysema, angiotensin receptor blocker
Brief summary
Evidence in animals shows that losartan can prevent or reverse inflammation and lung damage due to smoking. The goal of this study is to determine whether this drug which is also used to treat hypertension can stabilize or improve lung function in people who have from chronic obstructive pulmonary disease (COPD).
Detailed description
Participants will be given either losartan in a dose of 50-100 mg per day for a period of one year. During that time, they will have lung function tests, breathing tests, and computed tomograms of the chest. These tests will determine whether there is inflammation in the lung and whether there is progressive involvement of the lung with COPD.
Interventions
DRUGLosartan
Losartan 100 mg daily
DRUGPlacebo
Placebo pill daily
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Merck Sharp & Dohme LLC
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults with COPD who are either active or former smokers
Exclusion criteria
* Clinical requirement or history of intolerance of angiotensin receptor blockers, serious heart, liver, kidney, neurological disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Emphysema on CT Scan | Change between baseline and month 12. | Percent emphysema calculated as percent of CT voxels less than -950 HU measured at TLC. Analysis limited to patients with 5-35% emphysema on CT scan at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 (L) | Measured at Baseline and Month 12 | Change in FEV1 (L) post-bronchodilator from baseline to 12 months. Analysis includes only participants with 5-35% emphysema at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan Losartan 100 mg daily | 54 |
| Placebo Placebo 1 tablet daily | 52 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 7 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Losartan |
|---|---|---|---|
| Age, Continuous | 59.3 Years STANDARD_DEVIATION 9.8 | 58.8 Years STANDARD_DEVIATION 14 | 58.3 Years STANDARD_DEVIATION 10 |
| Emphysema on HRCT | 21 Participants | 45 Participants | 24 Participants |
| FEV1/FVC (%) | 49.9 percent STANDARD_DEVIATION 11.3 | 51.4 percent STANDARD_DEVIATION 15.4 | 52.9 percent STANDARD_DEVIATION 10.5 |
| FEV1 (L) | 1.42 L (BTPS) STANDARD_DEVIATION 0.46 | 1.49 L (BTPS) STANDARD_DEVIATION 0.69 | 1.57 L (BTPS) STANDARD_DEVIATION 0.52 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 30 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 76 Participants | 38 Participants |
| Sex: Female, Male Female | 25 Participants | 53 Participants | 28 Participants |
| Sex: Female, Male Male | 27 Participants | 53 Participants | 26 Participants |
| Smoking Status Current Smoker | 36 participants | 72 participants | 36 participants |
| Smoking Status Former Smoker | 16 participants | 34 participants | 18 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 1 / 52 |
| other Total, other adverse events | 19 / 54 | 24 / 52 |
| serious Total, serious adverse events | 7 / 54 | 18 / 52 |
Outcome results
Primary
Change in Percent Emphysema on CT Scan
Percent emphysema calculated as percent of CT voxels less than -950 HU measured at TLC. Analysis limited to patients with 5-35% emphysema on CT scan at baseline.
Time frame: Change between baseline and month 12.
Population: Participants with 5-35% emphysema on baseline CT scan
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Change in Percent Emphysema on CT Scan | -0.32 % Emphysema Whole Lung | Standard Deviation 3.7 |
| Placebo | Change in Percent Emphysema on CT Scan | 2.18 % Emphysema Whole Lung | Standard Deviation 4.9 |
Comparison: Participants demonstrating 5-35% emphysema on baseline CT scanp-value: 0.06t-test, 2 sided
Secondary
Change in FEV1 (L)
Change in FEV1 (L) post-bronchodilator from baseline to 12 months. Analysis includes only participants with 5-35% emphysema at baseline.
Time frame: Measured at Baseline and Month 12
Population: Participants with 5-35% emphysema at baseline who had HRCT scans performed both at baseline and at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Change in FEV1 (L) | -0.0879 L (BTPS) | Standard Deviation 0.163 |
| Placebo | Change in FEV1 (L) | -0.0581 L (BTPS) | Standard Deviation 0.167 |
Comparison: Participants with 5-35% emphysema at baselinep-value: 0.55t-test, 2 sided