Chronic Obstructive Pulmonary Disease and Allied ConditionsPhase 4ELASTICNCT01630200

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

A Phase 4 study testing Roflumilast in people with Chronic Obstructive Pulmonary Disease and Allied Conditions, run by LudwLudwig Boltzmann Institute for COPD and Respiratory Epidemiology at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Chronic Obstructive Pulmonary Disease and Allied Conditions
What is being tested?: Roflumilast
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 80 participants
Where: 1 siteAustria
Study dates: May 2012to Jan 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

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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

Trial locations and contacts

1 site in 1 country.

Austria1 site

Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital
Vienna, 1140

Other trials in Austria

About this study

Official title: Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial

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.

Conditions: Chronic Obstructive Pulmonary Disease and Allied Conditions
Being tested: Roflumilast, Placebo
Keywords: COPD, comorbidity, arterial stiffness, roflumilast
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RoflumilastDrug
Also called Daxas
Roflumilast coated tablet, 500µg oral application, once daily in the morning
PlaceboDrug
Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning

Study groups in NCT01630200
Study group	Role	What they receive
Roflumilast	Active comparator	Active arm including patients who receive the study drug (500µg Roflumilast once daily) Receives: Drug: Roflumilast
Placebo	Placebo comparator	Control arm including patients who receive the placebo tablet (once daily) Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: baseline, month 6

Secondary outcomes (8)

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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: baseline, month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2012Jan 2016

First posted28 Jun 2012 (estimated)
Study startMay 2012
Primary completionJan 2016
Study completionJan 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic Obstructive Pulmonary Disease and Allied ConditionsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01630200
Sponsor's protocol ID: ELASTIC2011
Acronym: ELASTIC
Status last verified: Jan 2019
First submitted: 4 Jun 2012
Last updated: 12 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 32725799

Study at a glance

From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial
ClinicalTrials.gov ID: NCT01630200
Acronym / sponsor ID: ELASTIC / ELASTIC2011
Conditions: Chronic Obstructive Pulmonary Disease and Allied Conditions
Keywords: COPD, comorbidity, arterial stiffness, roflumilast
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: LudwLudwig Boltzmann Institute for COPD and Respiratory EpidemiologyResearch network
Collaborators: Medical University of Vienna
Study start: May 2012
Primary completion: Jan 2016 (actual)
Study completion: Jan 2016 (actual)
First posted: 28 Jun 2012 (estimated)
Results: Posted 12 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Roflumilast	Active comparator	Drug: RoflumilastActive arm including patients who receive the study drug (500µg Roflumilast once daily)
Placebo	Placebo comparator	Drug: PlaceboControl arm including patients who receive the placebo tablet (once daily)

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (23 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RoflumilastAlso: DaxasRoflumilast coated tablet, 500µg oral application, once daily in the morning	Drug	Roflumilast
PlaceboPlacebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning	Drug	Placebo

Primary outcome

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.

8 secondary outcomes

Change From Baseline in Reactive Hyperemia Index at Month 6
Time frame: baseline, month 6
Change From Baseline in Augmentation Index at Month 6
Time frame: baseline, month 6
Change From Baseline in Matrix Metalloproteinase-9
Time frame: baseline, month 6
Change From Baseline in Asymmetric Dimethylarginine at Month 6
Time frame: baseline, month 6
Change From Baseline in Tumor Necrosis Factor-alpha at Month 6
Time frame: baseline, month 6
Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6
Time frame: baseline, month 6
Change From Baseline in 6-Minute Walk Test at Month 6
Time frame: baseline, month 6
Change From Baseline in COPD Assessment Test at Month 6
Time frame: baseline, month 6

Results and safety

Results posted to the registry on 12 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Roflumilast	40	33
Placebo	40	34

Primary outcome: Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6

Time frame: baseline, month 6. Least squares mean (95% Confidence Interval). Unit: meters per second (m/s)

Measure	Roflumilast n = 33	Placebo n = 34
Value	1.07 (0.98 to 1.17)	0.99 (0.91 to 1.08)

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Roflumilast	13 of 40 (32.5%)	27 of 40 (67.5%)	2 of 40
Placebo	9 of 40 (22.5%)	22 of 40 (55%)	1 of 40

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32725799Urban 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Otto C Burghuber, M.D. principal investigator

Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6 (time frame: baseline, month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01630200, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2019.