Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Inflammation, Atherosclerosis, Hydroxymethylglutaryl-coenzyme A Reductase Inhibitors
Brief summary
The purpose of this study is to investigate whether rosuvastatin improves measures of endothelial function, decreases measures of inflammation, and improves pulmonary function in patients with stable chronic obstructive pulmonary disease.
Interventions
DRUGRosuvastatin
10mg tablets, once daily in three months
DRUGPlacebo
1 tablet, once daily in three months
Sponsors
AstraZeneca
Haukeland University Hospital
University Hospital, Akershus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Stable COPD patients of both genders with no COPD exacerbations less than three weeks prior to inclusion * COPD stage I to IV after the GOLD criteria (Global Initiative for Chronic Obstructive Lung Disease) * Age between 40 and 80 years
Exclusion criteria
* Diagnosed lung disease other than COPD, except chronic asthmatic bronchitis and mild bronchiectasis without or few physical signs (diagnosed by high resolution CT) * History of or active coronary artery disease (CAD), cerebrovascular or peripheral vascular disease * History of or clinically significant congestive heart failure, valvular heart disease, clinically significant arrhythmias or conduction delays * History of uncontrolled arterial hypertension (defined as blood pressure above180/110 mmHg with or without the use of antihypertensive medication) * Body mass index \>40kg/m2 * History of diabetes mellitus, measured fasting glucose \> 11 mmol/L * History of Hypercholesterolemia, measured total cholesterol \> 8 mmol/L * Known poliomyelitis, motor neurone disease, cranial or temporal arteritis, stroke or myopathy * Neutropenia, anemia (Hb \< 8 g/100mL) * History of chronic renal failure, serum creatinine \> 176 micromol/L (2.0mg/dL) * Creatine kinase \> 3 times the upper limit of normal (ULN) * Acute or chronic liver disease (serum transaminases \> 3 times the ULN) * Pregnancy (oral examination and blood test prior to inclusion) * Active abuse of drugs or alcohol, poor compliance anticipated * Statin use within the last 4 weeks prior to study start or previously clear indication for statin use * Prior diagnosis of statin induced myopathy or hypersensitivity reaction to another hydroxymethylglutaryl-Coenzyme A-reductase inhibitor incl. Rosuvastatin * History of malignant disease of any kind within 5 years prior to inclusion. * History of uncontrolled hypothyroidism * Participation in another pharmaceutical or medical device clinical trial study less than 4 weeks prior inclusion. * Use concomitant of medications that are known to interact with Crestor. This includes the following medications: Warfarin and other coumarin (vitamin K antagonist) anticoagulants, Cyclosporin, Gemfibrozil and Antacid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change in Reactive Hyperemia Index (RHI) | Baseline to 3 months | Endothelial function assessed with peripheral arterial tonometry, expressed as the reactive hyperemia index (RHI) as a marker for subclinical atherosclerosis and future cardiovascular risk assessment. |
Secondary
| Measure | Time frame |
|---|---|
| Relative Change in FEV1 | Baseline to 3 months |
| Relative Change in High-sensitivity C-reactive Protein | Baseline to 3 months |
| Relative Change in Interleukin 6 | Baseline to 3 months |
Countries
Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rosuvastatin Rosuvastatin 10mg tablet | 47 |
| Placebo Placebo tablet | 47 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Rosuvastatin | Total |
|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 6.6 | 66 years STANDARD_DEVIATION 5.5 | 65 years STANDARD_DEVIATION 6.1 |
| Antihypertensive treatment No | 37 participants | 35 participants | 72 participants |
| Antihypertensive treatment Yes | 10 participants | 12 participants | 22 participants |
| Anti-inflammatory treatment No | 47 participants | 45 participants | 92 participants |
| Anti-inflammatory treatment Yes | 0 participants | 2 participants | 2 participants |
| BMI | 24 kg/m^2 STANDARD_DEVIATION 4.1 | 23 kg/m^2 STANDARD_DEVIATION 3.8 | 24 kg/m^2 STANDARD_DEVIATION 3.9 |
| Cholesterol | 5.7 mmol/L STANDARD_DEVIATION 1.1 | 5.5 mmol/L STANDARD_DEVIATION 0.9 | 5.6 mmol/L STANDARD_DEVIATION 1 |
| Current smoking No | 24 participants | 35 participants | 59 participants |
| Current smoking Yes | 23 participants | 12 participants | 35 participants |
| Diastolic blood pressure | 80 mmHg STANDARD_DEVIATION 10.3 | 79 mmHg STANDARD_DEVIATION 8.4 | 80 mmHg STANDARD_DEVIATION 9.4 |
| Estimated Glomerular Filtration Rate (eGFR) | 90.1 ml/min STANDARD_DEVIATION 29.4 | 82.4 ml/min STANDARD_DEVIATION 19.6 | 86.2 ml/min STANDARD_DEVIATION 25.1 |
| FEV1/FVC | 49 Percent of FVC STANDARD_DEVIATION 11.8 | 47 Percent of FVC STANDARD_DEVIATION 13.8 | 48 Percent of FVC STANDARD_DEVIATION 12.8 |
| FEV1, % of predicted | 52.1 Percent predicted value STANDARD_DEVIATION 18.8 | 48.3 Percent predicted value STANDARD_DEVIATION 18.9 | 50.2 Percent predicted value STANDARD_DEVIATION 18.9 |
| Forced expiratory volume at one second (FEV1) | 1.5 Liter STANDARD_DEVIATION 0.7 | 1.4 Liter STANDARD_DEVIATION 0.6 | 1.4 Liter STANDARD_DEVIATION 0.6 |
| Glucose | 5.1 mmol/L STANDARD_DEVIATION 0.7 | 5.0 mmol/L STANDARD_DEVIATION 0.6 | 5.0 mmol/L STANDARD_DEVIATION 0.6 |
| Haemoglobin | 14.0 g/dl STANDARD_DEVIATION 0.2 | 14.1 g/dl STANDARD_DEVIATION 1.4 | 14.0 g/dl STANDARD_DEVIATION 1.2 |
| HDL-C | 1.8 mmol/L STANDARD_DEVIATION 0.1 | 1.8 mmol/L STANDARD_DEVIATION 0.1 | 1.8 mmol/L STANDARD_DEVIATION 0.5 |
| Heart rate | 67 beats/min STANDARD_DEVIATION 10.9 | 68 beats/min STANDARD_DEVIATION 11.2 | 67 beats/min STANDARD_DEVIATION 11 |
| High-sensitivity C-reactive protein | 1.8 mg/L | 1.4 mg/L | 1.7 mg/L |
| History of asthma No | 34 participants | 38 participants | 72 participants |
| History of asthma Yes | 13 participants | 9 participants | 22 participants |
| History of hypertension No | 36 participants | 35 participants | 71 participants |
| History of hypertension Yes | 11 participants | 12 participants | 23 participants |
| Inhaled corticosteroids No | 13 participants | 11 participants | 24 participants |
| Inhaled corticosteroids Yes | 34 participants | 36 participants | 70 participants |
| Interleukin 6 | 3.4 pg/mL | 4.1 pg/mL | 3.7 pg/mL |
| LDL-C | 3.5 mmol/L STANDARD_DEVIATION 0.9 | 3.3 mmol/L STANDARD_DEVIATION 0.8 | 3.4 mmol/L STANDARD_DEVIATION 0.9 |
| Leucocyte count | 6.9 cells*10^9/L STANDARD_DEVIATION 1.7 | 6.6 cells*10^9/L STANDARD_DEVIATION 1.4 | 6.7 cells*10^9/L STANDARD_DEVIATION 1.6 |
| Long acting beta agonists No | 44 participants | 45 participants | 89 participants |
| Long acting beta agonists Yes | 3 participants | 2 participants | 5 participants |
| Long acting muscarinic antagonists No | 20 participants | 17 participants | 37 participants |
| Long acting muscarinic antagonists Yes | 27 participants | 30 participants | 57 participants |
| Oestrogen treatment No | 44 participants | 43 participants | 87 participants |
| Oestrogen treatment Yes | 3 participants | 4 participants | 7 participants |
| Pack-years | 35 pack-years STANDARD_DEVIATION 15.5 | 39 pack-years STANDARD_DEVIATION 16.1 | 37 pack-years STANDARD_DEVIATION 15.8 |
| Sex: Female, Male Female | 24 Participants | 21 Participants | 45 Participants |
| Sex: Female, Male Male | 23 Participants | 26 Participants | 49 Participants |
| Systolic blood pressure | 135 mmHg STANDARD_DEVIATION 20.1 | 131 mmHg STANDARD_DEVIATION 17.7 | 133 mmHg STANDARD_DEVIATION 18.9 |
| Triglycerides | 1.1 mmol/L STANDARD_DEVIATION 0.5 | 1.0 mmol/L STANDARD_DEVIATION 0.4 | 1.1 mmol/L STANDARD_DEVIATION 0.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 47 | 21 / 49 |
| serious Total, serious adverse events | 4 / 47 | 3 / 49 |
Outcome results
Primary
Relative Change in Reactive Hyperemia Index (RHI)
Endothelial function assessed with peripheral arterial tonometry, expressed as the reactive hyperemia index (RHI) as a marker for subclinical atherosclerosis and future cardiovascular risk assessment.
Time frame: Baseline to 3 months
Population: Complete case analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rosuvastatin | Relative Change in Reactive Hyperemia Index (RHI) | 6.65 percent change |
| Placebo | Relative Change in Reactive Hyperemia Index (RHI) | -1.27 percent change |
p-value: 0.292ANCOVA
Secondary
Relative Change in FEV1
Time frame: Baseline to 3 months
Population: Complete case analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rosuvastatin | Relative Change in FEV1 | 2.6 percent change |
| Placebo | Relative Change in FEV1 | -1.1 percent change |
p-value: 0.462ANCOVA
Secondary
Relative Change in High-sensitivity C-reactive Protein
Time frame: Baseline to 3 months
Population: Complete case analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rosuvastatin | Relative Change in High-sensitivity C-reactive Protein | -20.0 percent change |
| Placebo | Relative Change in High-sensitivity C-reactive Protein | 11.0 percent change |
p-value: 0.017ANCOVA
Secondary
Relative Change in Interleukin 6
Time frame: Baseline to 3 months
Population: Complete case analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rosuvastatin | Relative Change in Interleukin 6 | 8 percent change |
| Placebo | Relative Change in Interleukin 6 | 30 percent change |
p-value: 0.028ANCOVA