Chronic Obstructive Pulmonary Disease With (Acute) ExacerbationPhase 2TREATNCT01473758
Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease
A Phase 2 study testing Roflumilast in people with Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation, run by AstraZeneca at 2 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
- 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
- 81 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Feb 2012to Mar 2014
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 14Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha
London, NW3 2PF
Study site
London
About this study
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
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.
Read the 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.
- Being tested
- Roflumilast, Placebo
- Keywords
- COPD, Chronic obstructive pulmonary disease, 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
500 µg tablet, od, oral administration in the morning after breakfast
PlaceboDrug
tablet, od, oral administration in the morning after breakfast
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast | Active comparator | added on to standard therapy for acute COPD exacerbations Receives: Drug: Roflumilast |
| Placebo | Placebo comparator | added on to standard therapy for acute COPD exacerbations Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
Measured: Baseline and Day 14
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
Measured: Baseline and Day 14
Secondary outcomes (56)
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) and were determined with a Neubauer hemocytometer.
Measured: Day 14
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) and were determined with a Neubauer hemocytometer.
Measured: Day 14
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of neutrophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction. A negative change from Baseline indicates improvement.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of macrophages was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of eosinophils was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Aliquots of a cell suspension prepared from the sputum sample were used to prepare cytospin slides that were stained with Diff-Quik for differential cell counts. 100 cells were counted and the percentage of lymphocytes was determined. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-6 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker IL-8 was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker MPO was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Sputum samples were collected and processed at the investigational site according to their standard procedures. Sputum inflammatory marker Neutrophil Elastase was quantified by commercial sandwich enzyme-linked immunosorbent assays (ELISA). A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Blood was collected and serum biomarker IL-6 was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Blood was collected and serum biomarker IL-1β was quantified using commercial sandwich ELISA. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Blood was collected and serum biomarker CRP was measured using Roche Modular Analytics E 170 Module. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Biomarker Plasma fibrinogen was determined using the method described by Clauss. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Blood was collected and analyzed for serum glucose levels. A negative change from Baseline indicated improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Forced vital capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Pulmonary function testing was performed using spirometry. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in FEV1/FVC (Initial Approach)
FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in FEV1/FVC (Extended Approach)
FEV1/FVC is the percentage of the vital capacity which is expired in the first second of maximal expiration. In healthy patients the FEV1/FVC is usually around 70%. A positive change from Baseline indicates an improvement. A Mixed Model Repeated Measurement (MMRM) was used for analysis with Baseline value, treatment, visit, and treatment by visit interaction as covariates.
Measured: Baseline and Day 7, Day 14, Day 28 and Day 56
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst).
Measured: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
The CAT is a short, validated, patient-completed questionnaire to assess the impact of COPD on health status. It comprises 8 questions that cover a broad range of effects of COPD on patients' health. Each question is scored in a range between 0 and 5, with the higher end indicating a higher impact of COPD on the patient's wellbeing. The CAT Total score ranges from 0 best) to 40 (Worst). A negative change from Baseline indicates improvement. Covariates for MMRM are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status.
Measured: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Initial Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Exacerbations of Chronic Pulmonary Disease Test (EXACT-PRO) Weekly Averages (Extended Approach)
The EXACT-PRO questionnaire is a new, validated, and standardized measure to evaluate the frequency, severity, and duration of COPD exacerbations. It is a 14-item daily diary, and scores range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are baseline value, treatment, time point, treatment by time point and baseline by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Initial Approach)
Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Peak Expiratory Flow (PEF) Weekly Average (Extended Approach)
Morning post-medication PEF (the best of 3 attempts measured with a mini-Wright peak-flow meter) was recorded in a daily diary. A positive change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Symptom Score Weekly Average (Initial Approach)
Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Symptom Score Weekly Average (Extended Approach)
Any increase in the following respiratory symptoms: dyspnea, sputum purulence, sputum amount, wheeze, sore throat, cough, fever, symptoms of a common cold, ie, nasal congestion and discharge over the previous 24 hours were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Treatment Score Weekly Average (Initial Approach)
Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Treatment Score Weekly Average (Extended Approach)
Any changes in the participant's usual treatment were recorded in a daily diary. Diaries Symptom Score range from 0 to 100, with higher scores indicating worse health status. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Initial Approach)
Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Diaries Hours Out of the Home Weekly Average (Extended Approach)
Estimates of the length of time the participants were out of their own home on the previous day were recorded in a daily diary. A negative change from Baseline indicates improvement. Covariates for Mixed Model Repeated Measurement (MMRM) are stable state value, treatment, time point, and treatment by time point interaction.
Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Exacerbation Length (Initial Approach)
Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.
Measured: 8 Weeks
Exacerbation Length (Extended Approach)
Exacerbation length is the period from start of increased symptoms to end of increased symptoms; the last day of an exacerbation was to be followed by 2 days without symptom entries in the diary.
Measured: 8 Weeks
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Initial Approach)
Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Days 14 and 28
Change From Baseline in Aortic Pulse Wave Velocity in a Subset of Participants (Extended Approach)
Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness. A negative change from Baseline indicates improvement. Covariates for MMRM are baseline value, treatment, visit, and treatment by visit interaction.
Measured: Baseline and Days 14 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2011 (estimated)
- Study startFeb 2012
- Primary completionMar 2014
- Study completionMar 2014
Why it stopped: Company decision: No Safety or Efficacy Concerns
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 With (Acute) ExacerbationStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01473758
- Sponsor's protocol ID
- RO-2455-405-RD
- Other IDs
- 2011-002905-31, U1111-1137-4023, 11/SC/0494
- Acronym
- TREAT
- Status last verified
- Aug 2016
- First submitted
- 31 Oct 2011
- Last updated
- 14 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28146642
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01473758
- Acronym / sponsor ID
- TREAT / RO-2455-405-RD
- Keywords
- COPD, Chronic obstructive pulmonary disease, Roflumilast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision: No Safety or Efficacy Concerns
- Enrolment
- 81 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 17 Nov 2011 (estimated)
- Results
- Posted 24 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roflumilast | Active comparator | Drug: Roflumilastadded on to standard therapy for acute COPD exacerbations |
| Placebo | Placebo comparator | Drug: Placeboadded on to standard therapy for acute COPD exacerbations |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Roflumilast500 µg tablet, od, oral administration in the morning after breakfast | Drug | Roflumilast |
| Placebotablet, od, oral administration in the morning after breakfast | Drug | Placebo |
Primary outcome
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)
Time frame: Baseline and Day 14
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)
Time frame: Baseline and Day 14
Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.
56 secondary outcomes
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)
Time frame: Day 14
Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)
Time frame: Day 14
Change From Baseline in Sputum Marker Total Cells (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Total Cells (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Neutrophils (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Macrophages (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Macrophages (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Eosinophils (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Eosinophils (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Lymphocyte (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Percentage of Lymphocytes (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-6 (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Interleukin (IL)-8 (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Myeloperoxidase (MPO) (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Sputum Marker Concentration of Neutrophil Elastase (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Interleukin (IL)-6 (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Interleukin-1 Beta (IL-1β) (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker IL-1β (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker C-reactive Protein (CRP) (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Fibrinogen (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Fibrinogen (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Glucose (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Blood Biomarker Glucose (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Expiratory Volume (FEV1) (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Expiratory Volume (FEV1) (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Vital Capacity (FVC) (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in Forced Vital Capacity (FVC) (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in FEV1/FVC (Initial Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Change From Baseline in FEV1/FVC (Extended Approach)
Time frame: Baseline and Day 7, Day 14, Day 28 and Day 56
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Initial Approach)
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Change From Stable State in Chronic Obstructive Pulmonary Assessment Test (CAT) Weekly Averages (Extended Approach)
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7 and 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28146642Mackay 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.
Related trials for Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
RecruitingPhase 2
Rademikibart IV for Acute Asthma and COPD Exacerbation
Asthma Acute, COPD Exacerbation Acute
RecruitingObservational study
Characteristics and Outcomes of Patients Admitted to ICU for a Severe Acute Exacerbation of COPD.
COPD Exacerbation, ICU
RecruitingObservational study
Study of Hospitalised Patients With Acute Respiratory Conditions
Acute Respiratory Disease, COPD Exacerbation Acute
Recruiting
Controlled Versus Standard Oxygen Therapy in ICU Patients With Acute Exacerbation of COPD
Chronic Obstructive Pulmonary Disease (COPD), Acute Exacerbation of COPD
RecruitingObservational study
Interoception and Symptom Perception in Acute COPD Exacerbation
Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Interoceptive Awareness
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.
Medical Director Clinical Science study director
Takeda
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Roflumilast in people with Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation, run by AstraZeneca at 2 sites in United Kingdom.
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 14 inclusion and 0 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: stopped early, as of the sponsor's last update on 14 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Oct 2016). 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 Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach) (time frame: Baseline and Day 14). The study lists 2 primary outcomes in all. 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 NCT01473758, 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 14 Feb 2017.