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Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD) (ELASTIC)

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ClinicalTrials.gov Identifier: NCT01630200
Recruitment Status : Completed
First Posted : June 28, 2012
Results First Posted : April 12, 2019
Last Update Posted : April 12, 2019
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology

Tracking Information
First Submitted Date  ICMJE June 4, 2012
First Posted Date  ICMJE June 28, 2012
Results First Submitted Date  ICMJE August 26, 2017
Results First Posted Date  ICMJE April 12, 2019
Last Update Posted Date April 12, 2019
Study Start Date  ICMJE May 2012
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6 [ Time Frame: baseline, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2012)
carotid femoral-Pulse Wave Velocity [ Time Frame: 6 month ]
Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively with the well validated SphygmoCor system (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
  • Change From Baseline in Reactive Hyperemia Index at Month 6 [ Time Frame: baseline, 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.
  • Change From Baseline in Augmentation Index at Month 6 [ Time Frame: baseline, 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.
  • Change From Baseline in Matrix Metalloproteinase-9 [ Time Frame: baseline, month 6 ]
    Circulating levels of Matrix Metalloproteinase-9 (MMP-9) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay
  • Change From Baseline in Asymmetric Dimethylarginine at Month 6 [ Time Frame: baseline, month 6 ]
    Circulating levels of Asymmetric dimethylarginine (ADMA) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay
  • Change From Baseline in Tumor Necrosis Factor-alpha at Month 6 [ Time Frame: baseline, month 6 ]
    Circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay
  • Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6 [ Time Frame: baseline, month 6 ]
    Forced Expiratory Volume in 1 second (FEV1) will be measured via standardized Spirometry
  • Change From Baseline in 6-Minute Walk Test at Month 6 [ Time Frame: baseline, month 6 ]
    6-Minute Walk Test (6MWT) will be assessed to quantify functional exercise capacity following the standardized protocol of the American Thoracic Society
  • Change From Baseline in COPD Assessment Test at Month 6 [ Time Frame: baseline, 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2012)
  • Reactive Hyperemia Index [ Time Frame: 6 month ]
    Endothelial dysfunction will be assessed by means of the EndoPat device (Itamar Medical Ltd). 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.
  • Augmentation Index [ Time Frame: 6 month ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD)
Official Title  ICMJE Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease and Allied Conditions
Intervention  ICMJE
  • Drug: Roflumilast
    Roflumilast coated tablet, 500µg oral application, once daily in the morning
    Other Name: Daxas
  • Drug: Placebo
    Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
Study Arms  ICMJE
  • Active Comparator: Roflumilast
    Active arm including patients who receive the study drug (500µg Roflumilast once daily)
    Intervention: Drug: Roflumilast
  • Placebo Comparator: Placebo
    Control arm including patients who receive the placebo tablet (once daily)
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 27, 2012)
80
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Over 40 years of age
  • Smoking history of at least 10 pack years
  • Chronic obstructive pulmonary disease at Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II - IV diagnosed according to standard criteria.
  • History of at least one COPD exacerbation requiring systemic corticosteroid treatment or hospitalisation in the previous year

Exclusion Criteria:

  • Insufficient compliance to study medication (≤70% of tablets used) during 4 weeks run-in period
  • History of acute exacerbation 4 weeks prior to run-in period
  • Diagnosis of alpha-1-antitrypsin deficiency
  • Diagnosis of asthma
  • Acute respiratory infections (e.g. pneumonia)
  • Severe acute infectious diseases (e.g. active hepatitis, HIV)
  • Lung cancer
  • Bronchiectasis
  • Interstitial lung disease
  • Any other relevant lung disease
  • Acute myocardial infarction
  • Systolic left ventricular dysfunction
  • Congestive heart failure New York Heart Association Functional Classification (NYHA) severity grade IV
  • Haemodynamically significant cardiac arrhythmias or heart valve deformations
  • Peripheral arterial occlusive disease
  • Acute or chronic renal/hepatic failure
  • Active malignancy
  • Autoimmune disease
  • Pregnant or breastfeeding women
  • Women no using or not willing to use adequate contraceptive measures for the duration of the trial
  • Hypersensitivity to study medication or placebo
  • Severe psychiatric or neurological disorders or history of depression associated with suicidal ideation or behaviour
  • Galactose intolerance, lactase insufficiency or glucose-galactose malabsorption
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01630200
Other Study ID Numbers  ICMJE ELASTIC2011
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Study Sponsor  ICMJE LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Collaborators  ICMJE Medical University of Vienna
Investigators  ICMJE
Principal Investigator: Otto C Burghuber, M.D. Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna
PRS Account LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP