Clinical trial NCT01473758: Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Official title: Effect of Roflumilast 500 μg Tablets Once Daily at Acute COPD Exacerbations Treated With Standard Therapy of Oral Steroids and Antibiotics. A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
Keywords: COPD
Chronic obstructive pulmonary disease
Roflumilast
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-11-17
Enrollment: 81
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to investigate if roflumilast can reduce the neutrophilic inflammation at acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). In addition, the potential benefit of roflumilast on severity and recovery periods of acute COPD exacerbations will be assessed using patient diaries and questionnaires.

Detailed description: Participants will be asked whether they agree to participate in the measurements of arterial stiffness. Participants who agree will be included in the substudy, with the target of 60 patients with arterial stiffness measurements to complete the trial.

Study was terminated due to difficulty in identifying further eligible patients for this exploratory study within a reasonable time.

Eligibility criteria: Inclusion Criteria:

* Written informed consent (IC)
* Age ≥ 40 years
* History of COPD for at least 12 months prior to enrollment (Visit V0)
* Chronic productive cough for 3 months in each of the 2 years prior to enrollment (if other causes of productive cough have been excluded) and/or an exacerbation with predominantly bronchitic symptoms at enrollment
* Presentation of an acute exacerbation of COPD that will be associated with increased sputum volume or change in sputum colour
* Documented fixed airway obstruction determined by an FEV1/FVC ratio (post-bronchodilator) \< 70% (if a pulmonary function test is not possible at Visit V0 a previous measurement can be taken which must not be older than 6 months)
* Former smoker (defined as: smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 10 pack years

Main Exclusion Criteria:

* Diagnosis of asthma and/or other relevant lung disease
* Known alpha-1-antitrypsin deficiency
* Recurrent exacerbations (within 8 weeks of a preceding exacerbation)
* Treatment of current exacerbation with oral corticosteroids and/or antibiotics already started at enrollment
* Treatment with PDE4 inhibitors within 3 months prior to Visit V0
* Other protocol-defined exclusion criteria may apply

Primary outcomes:
measure: Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)
timeFrame: Baseline and Day 14
measure: Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
timeFrame: Baseline and Day 14
Secondary outcomes:
measure: Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)
timeFrame: Day 14
measure: Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)
timeFrame: Day 14
measure: Change From Baseline in Sputum Marker Total Cells (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Total Cells (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Glucose (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Blood Biomarker Glucose (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in FEV1/FVC (Initial Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Change From Baseline in FEV1/FVC (Extended Approach)
timeFrame: Baseline and Day 7, Day 14, Day 28 and Day 56
measure: Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
measure: Exacerbation Length (Initial Approach)
timeFrame: 8 Weeks
measure: Exacerbation Length (Extended Approach)
timeFrame: 8 Weeks
measure: Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)
timeFrame: Baseline and Days 14 and 28
measure: Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)
timeFrame: Baseline and Days 14 and 28
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha
city: London
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Mackay AJ, Patel ARC, Singh R, Sapsford RJ, Donaldson GC, Prasad N, Goehring UM, Nip TK, Wedzicha JA. Randomized Double-Blind Controlled Trial of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Sep 1;196(5):656-659. doi: 10.1164/rccm.201612-2518LE. No abstract available.