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| Name | Class |
|---|---|
| Medical University of Vienna | OTHER |
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Chronic obstructive pulmonary disease is associated with a low grade systemic inflammatory process. Systemic inflammation is hypothesized to maintain cardiovascular morbidity and mortality in COPD. Early changes of vascular integrity can be detected via markers of subclinical atherosclerosis.
Selective Inhibition of phosphodiesterase subtype 4 describes a promising therapeutic option in COPD with beneficial impact on lung function and exacerbation rate. Moreover, an anti-inflammatory effect of phosphodiesterase-4 inhibition was confirmed by recent data.
The aim of this study is to assess the effects of the phosphodiesterase-4 inhibitor Roflumilast on firstly surrogates of subclinical atherosclerosis and secondly markers of systemic inflammation in the peripheral circulation of patients with stable chronic obstructive pulmonary disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Roflumilast | Active Comparator | Active arm including patients who receive the study drug (500µg Roflumilast once daily) |
|
| Placebo | Placebo Comparator | Control arm including patients who receive the placebo tablet (once daily) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Roflumilast | Drug | Roflumilast coated tablet, 500µg oral application, once daily in the morning |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6 | Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively via applanation tonometry (AtCor Medical, Sydney, Australia). Wave propagation time will be calculated by the system software, using an ECG-gated reference frame. Aortic PWV is defined as the distance between two recording sites (i.e. common carotid- and femoral artery) divided by the wave propagation time. | baseline, month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Reactive Hyperemia Index at Month 6 | Endothelial dysfunction will be assessed by Flow Mediated Dilation via the Endopat device. This validated system measures the pulse wave amplitudes at the tip of both index fingers. The dominant arm will be occluded for 5 minutes by a sphygmomanometric cuff. After cuff deflation the pulse wave amplitude will be assessed to finally calculate the ratio of pulse wave amplitude before and after cuff-induced hyperemia. The so called reactive hyperemia index represents endothelial dysfunction at the level of conduit as well as resistance vessels. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Otto C Burghuber, M.D. | Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital | Vienna | 1140 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32725799 | Derived | Urban MH, Kreibich N, Gleiss A, Funk GC, Hartl S, Burghuber OC. Effects of roflumilast on arterial stiffness in COPD (ELASTIC): A randomized trial. Respirology. 2021 Feb;26(2):153-160. doi: 10.1111/resp.13914. Epub 2020 Jul 28. |
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After inclusion, patients entered a 4 week, single-masked run-in period with placebo application. Given sufficient compliance to medication (≥70% of tablets) patients were randomized to receive either the study drug (Roflumilast 500 μg) or placebo in a double-masked manner.
Patients were recruited from the Department of Respiratory and Critical Care Medicine in the Otto Wagner Hospital in Vienna and supporting centres (hospitals, outpatient clinics, respiratory specialists).
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| ID | Title | Description |
|---|---|---|
| FG000 | Roflumilast | Active arm including patients who receive the study drug (500µg Roflumilast once daily) Roflumilast: Roflumilast coated tablet, 500µg oral application, once daily in the morning |
| FG001 | Placebo | Control arm including patients who receive the placebo tablet (once daily) Placebo: Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Roflumilast | Active arm including patients who receive the study drug (500µg Roflumilast once daily) Roflumilast: Roflumilast coated tablet, 500µg oral application, once daily in the morning |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6 | Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively via applanation tonometry (AtCor Medical, Sydney, Australia). Wave propagation time will be calculated by the system software, using an ECG-gated reference frame. Aortic PWV is defined as the distance between two recording sites (i.e. common carotid- and femoral artery) divided by the wave propagation time. | Posted | Least Squares Mean | 95% Confidence Interval | meters per second (m/s) | baseline, month 6 |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Roflumilast | Active arm including patients who receive the study drug (500µg Roflumilast once daily) Roflumilast: Roflumilast coated tablet, 500µg oral application, once daily in the morning |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Amyotrophic lateral sclerosis | Nervous system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Weight loss | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Matthias Urban | Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology | +43(0)6508125980 | matthias.urban1@gmx.net |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C424423 | Roflumilast |
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| Placebo | Drug | Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning |
|
| baseline, month 6 |
| Change From Baseline in Augmentation Index at Month 6 | The curve of the peripheral pressure wave will be recorded from the radial artery. Augmentation index (Aix) will be calculated from the generated central aortic pressure waveform via pulse wave analysis function. To correct for respective influences, Aix will be adjusted for a heart rate of 75 bpm. Appropriate intra observer validity will be assured via an operator index ≥ 80. | baseline, month 6 |
| Change From Baseline in Matrix Metalloproteinase-9 | Circulating levels of Matrix Metalloproteinase-9 (MMP-9) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay | baseline, month 6 |
| Change From Baseline in Asymmetric Dimethylarginine at Month 6 | Circulating levels of Asymmetric dimethylarginine (ADMA) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay | baseline, month 6 |
| Change From Baseline in Tumor Necrosis Factor-alpha at Month 6 | Circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay | baseline, month 6 |
| Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6 | Forced Expiratory Volume in 1 second (FEV1) will be measured via standardized Spirometry | baseline, month 6 |
| Change From Baseline in 6-Minute Walk Test at Month 6 | 6-Minute Walk Test (6MWT) will be assessed to quantify functional exercise capacity following the standardized protocol of the American Thoracic Society | baseline, month 6 |
| Change From Baseline in COPD Assessment Test at Month 6 | COPD Assessment Test (CAT) will be assessed to quantify patients disease related symptoms and to measure the impact of COPD on a patient's life, and how this changes over time. CAT is a standardised and validated patient questionaire comprising 8 distinct questions about different COPD-related symptoms. Each symptom is quantified by the patient on a numeric scale ranging from 0 to 5. Each symptom gives a number of points quantified as interval data without decimal places. The 8 different numbers of points are added to a total number expressed as the final points of the CAT score. The minimum achievable number of points is 0 and the maximum achievable number of points is 40. Higher values provide high symptoms and worse outcome, lower values provide low symptoms and better outcome. | baseline, month 6 |
Control arm including patients who receive the placebo tablet (once daily)
Placebo: Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Control arm including patients who receive the placebo tablet (once daily) Placebo: Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning |
|
|
| Secondary | Change From Baseline in Reactive Hyperemia Index at Month 6 | Endothelial dysfunction will be assessed by Flow Mediated Dilation via the Endopat device. This validated system measures the pulse wave amplitudes at the tip of both index fingers. The dominant arm will be occluded for 5 minutes by a sphygmomanometric cuff. After cuff deflation the pulse wave amplitude will be assessed to finally calculate the ratio of pulse wave amplitude before and after cuff-induced hyperemia. The so called reactive hyperemia index represents endothelial dysfunction at the level of conduit as well as resistance vessels. | Posted | Least Squares Mean | 95% Confidence Interval | Index | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in Augmentation Index at Month 6 | The curve of the peripheral pressure wave will be recorded from the radial artery. Augmentation index (Aix) will be calculated from the generated central aortic pressure waveform via pulse wave analysis function. To correct for respective influences, Aix will be adjusted for a heart rate of 75 bpm. Appropriate intra observer validity will be assured via an operator index ≥ 80. | Posted | Least Squares Mean | 95% Confidence Interval | Index | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in Matrix Metalloproteinase-9 | Circulating levels of Matrix Metalloproteinase-9 (MMP-9) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay | Posted | Least Squares Mean | 95% Confidence Interval | ng/ml | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in Asymmetric Dimethylarginine at Month 6 | Circulating levels of Asymmetric dimethylarginine (ADMA) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay | Posted | Least Squares Mean | 95% Confidence Interval | µmol/l | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in Tumor Necrosis Factor-alpha at Month 6 | Circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay | Posted | Least Squares Mean | 95% Confidence Interval | pg/ml | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6 | Forced Expiratory Volume in 1 second (FEV1) will be measured via standardized Spirometry | Posted | Least Squares Mean | 95% Confidence Interval | % predicted | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in 6-Minute Walk Test at Month 6 | 6-Minute Walk Test (6MWT) will be assessed to quantify functional exercise capacity following the standardized protocol of the American Thoracic Society | Posted | Least Squares Mean | 95% Confidence Interval | meters | baseline, month 6 |
|
|
|
| Secondary | Change From Baseline in COPD Assessment Test at Month 6 | COPD Assessment Test (CAT) will be assessed to quantify patients disease related symptoms and to measure the impact of COPD on a patient's life, and how this changes over time. CAT is a standardised and validated patient questionaire comprising 8 distinct questions about different COPD-related symptoms. Each symptom is quantified by the patient on a numeric scale ranging from 0 to 5. Each symptom gives a number of points quantified as interval data without decimal places. The 8 different numbers of points are added to a total number expressed as the final points of the CAT score. The minimum achievable number of points is 0 and the maximum achievable number of points is 40. Higher values provide high symptoms and worse outcome, lower values provide low symptoms and better outcome. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | baseline, month 6 |
|
|
|
| 2 |
| 40 |
| 13 |
| 40 |
| 27 |
| 40 |
| EG001 | Placebo | Control arm including patients who receive the placebo tablet (once daily) Placebo: Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning | 1 | 40 | 9 | 40 | 22 | 40 |
| Atrial fibrillation | Cardiac disorders | Non-systematic Assessment |
|
| Bronchoscopic lung volume reduction | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pulmonary nodule | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Carotid artery stenosis | Vascular disorders | Non-systematic Assessment |
|
| Diabetic vasculopathy | Vascular disorders | Non-systematic Assessment |
|
| Bronchoscopy for bronchiectasis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Death (unknown origin) | Investigations | Non-systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | Non-systematic Assessment |
|
| Hypercapnic decompensation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| insomnia | Nervous system disorders | Non-systematic Assessment |
|
| Polypectomy | Gastrointestinal disorders | Non-systematic Assessment |
|
| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Common cold | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Loss of appetite | Gastrointestinal disorders | Non-systematic Assessment |
|
| Cramps in upper/lower extremities | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Nervous system disorders | Non-systematic Assessment |
|
| Insomnia | Nervous system disorders | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | Non-systematic Assessment |
|
| Pulmonary embolism | Vascular disorders | Non-systematic Assessment |
|
| Influenca | Infections and infestations | Non-systematic Assessment |
|
| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Obstipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Herniated vertebral disc | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
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| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |