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Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease (TREAT)

This study is currently recruiting participants.
Verified January 2013 by Takeda Global Research & Development Center, Inc.
Sponsor:
Information provided by (Responsible Party):
Takeda Global Research & Development Center, Inc. ( Takeda Pharma A/S )
ClinicalTrials.gov Identifier:
NCT01473758
First received: October 31, 2011
Last updated: January 4, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
 Drug: Roflumilast
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Roflumilast
U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:
  • Change in sputum neutrophil counts [cells/g sputum] from Day 1 to Day 14 post exacerbation [ Time Frame: Day 1 to Day 14 ] [ Designated as safety issue: No ]
    Assessment will be done at Day 14 after randomisation


Secondary Outcome Measures:
  • Change in sputum inflammatory markers [ Time Frame: Day 1 to Day 7, Day 14, Day 28, Day 56 ] [ Designated as safety issue: No ]

    • Change for the following sputum inflammatory markers:

      • total and differential cell counts (absolute [cells/g sputum] and percentage [%])

        • neutrophils (except for change addressed in primary outcome)
        • macrophages
        • eosinophils
        • lymphocytes
      • Sputum concentrations of interleukin (IL)-6, IL-8, myeloperoxidase (MPO), neutrophil elastase.
    • Proportion of patients whose sputum neutrophil counts have returned to stable state levels at Day 14 post exacerbation.

  • Change in blood biomarkers [ Time Frame: Day 1 to Day 7, Day 14, Day 28, Day 56 ] [ Designated as safety issue: No ]

    Change for the blood concentration of the following biomarkers:

    • C-reactive protein (CRP)

    • fibrinogen

    • IL-6 and IL-1β

    • glucose


  • Change in pulmonary function [ Time Frame: Day 1 to Day 7, Day 14, Day 28, Day 56 ] [ Designated as safety issue: No ]

    Change for the following spirometry measurements:

    • Forced expiratory volume in the first second (FEV1)

    • forced vital capacity (FVC)

    • FEV1/FVC


  • Diary outcomes [ Time Frame: During treatment and follow-up period (up to 56 days) ] [ Designated as safety issue: No ]

    Diary outcomes will include the following:

    • outcomes with respect to exacerbations
    • time course on a daily basis and changes on a weekly basis for PEF, respiratory symptoms and hours spent out of house

  • Patient-reported outcomes [ Time Frame: During treatment and follow-up period (up to 56 days) ] [ Designated as safety issue: No ]

    Time course on a daily basis and changes on a weekly basis for the following:

    • COPD Assessment Test (CAT)

    • EXAcerbations of Chronic pulmonary disease Test-Patient-Reported Outcome (EXACT-PRO) questionnaire.


  • Change from Baseline in aortic pulse wave velocity in a subset of participants [ Time Frame: Baseline and Days 14 and 28. ] [ Designated as safety issue: No ]
    Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness.


Estimated Enrollment: 140
Study Start Date: February 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Roflumilast
added on to standard therapy for acute COPD exacerbations
 Drug: Roflumilast
500 µg tablet, od, oral administration in the morning after breakfast
Placebo Comparator: Placebo
added on to standard therapy for acute COPD exacerbations
 Drug: Placebo
tablet, od, oral administration in the morning after breakfast

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01473758

Contacts
Contact: Takeda Study Registration Call Center +1-800-778-2860 medicalinformation@tpna.com

Locations
United Kingdom
Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha Recruiting
London, United Kingdom, NW3 2PF
Sponsors and Collaborators
Takeda Pharma A/S
  More Information

No publications provided

Responsible Party: Takeda Global Research & Development Center, Inc. ( Takeda Pharma A/S )
ClinicalTrials.gov Identifier: NCT01473758     History of Changes
Other Study ID Numbers: RO-2455-405-RD, 2011-002905-31, U1111-1137-4023
Study First Received: October 31, 2011
Last Updated: January 4, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda Global Research & Development Center, Inc.:
COPD
Chronic obstructive pulmonary disease
Roflumilast

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 22, 2013