Tumour necrosis factor-alpha (TNF-alpha) antagonists for acute exacerbations of chronic obstructive pulmonary disease (COPD)
| ISRCTN | ISRCTN60472167 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60472167 |
| ClinicalTrials.gov (NCT) | NCT00789997 |
| Protocol serial number | 2007791-01H; MCT-90167 |
| Sponsor | Ottawa Hospital Research Institute (OHRI) (Canada) |
| Funder | Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-90167) |
- Submission date
- 13/01/2010
- Registration date
- 19/01/2010
- Last edited
- 20/02/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Shawn Aaron
Scientific
Scientific
Ottawa Hospital
501 Smyth Road
Ottawa
K1H 8L6
Canada
| saaron@ohri.ca |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multicentre placebo-controlled randomised trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Tumour necrosis factor-alpha (TNF-alpha) antagonists for acute exacerbations of chronic obstructive pulmonary disease (COPD): a randomised, double-blind, placebo-controlled pilot trial |
| Study objectives | The purpose of this study is to determine whether treatment with antibiotics plus a tumour necrosis factor-alpha (TNF-alpha) antagonist will provide more effective treatment for acute chronic obstructive pulmonary disease (COPD) exacerbation compared to the current standard treatment of antibiotics plus prednisone. |
| Ethics approval(s) | Ottawa Hospital Research Ethics Board, 08/05/2008, ref: 2007791-01H. All other centres will seek ethics approval before recruiting participants. |
| Health condition(s) or problem(s) studied | Chronic obstructive pulmonary disease (COPD) |
| Intervention | Arm: Etanercept Drug: Etanercept and levofloxacin Levofloxacin 750 mg daily for 10 days and etanercept 50 mg subcutaneous given on the day of randomisation and one week later and placebo prednisone capsule, 1 daily for 10 days. Arm: Prednisone Drug: Prednisone and levofloxacin Levofloxacin 750 mg daily for 10 days and prednisone 40 mg daily for 10 days and placebo subcutaneous injections given on day of randomisation and one week later. Total duration of treatment: 10 days Total duration of follow-up: 90 days |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Etanercept, levofloxacin, prednisone |
| Primary outcome measure(s) |
Change in lung function (FEV1) from day 0 to day 14 |
| Key secondary outcome measure(s) |
1. Time to treatment failure assessed within a 90 day period |
| Completion date | 01/01/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 80 |
| Key inclusion criteria | Both inpatients and outpatients with acute COPD exacerbation will be selected for randomisation. Patients will be considered to fulfill the diagnosis of AECOPD if they meet the following five criteria: 1. Patients must have had a previous diagnosis of chronic bronchitis, emphysema or COPD established by a physician 2. Patients must have evidence of airflow obstruction on presentation, defined as a forced expiratory volume in one second (FEV1) equal to or less than 70% of predicted and a FEV1/forced vital capacity (FVC) ratio less 70% 3. Patients must be greater than 35 years old, either sex 4. Patients must have a minimum history of 10 pack years smoking 5. Patients must be experiencing an acute exacerbation of COPD and must meet at least two of the following three clinical criteria for acute COPD exacerbation as defined by Anthonisen: 5.1. Increased chronic baseline dyspnoea 5.2. Increased sputum volume 5.3. Increased sputum purulence The above complaints had to have necessitated the emergency department or physician visit. |
| Key exclusion criteria | 1. Respiratory failure necessitating admission to an intensive care unit or necessitating use of mechanical invasive or non-invasive (bilevel positive airway pressure [BIPAP]) mechanical ventilation 2. Physician diagnosed asthma 3. Any patient who has used oral or injectable corticosteroids during the month preceding trial entry will be excluded, except for patients who have received a single dose of oral or injectable steroids (up to the equivalent of 125 mg of methylprednisolone) in the emergency department prior to randomisation. (Note that standard clinical practice in emergency departments is to treat these patients with oral or intravenous steroids on presentation to the ED. Since it will be functionally impossible to randomise patients prior to initial ED treatment we will allow randomisation of patients who have been given a single dose of steroid in the ED.) 4. History of chronic lung disease other than COPD. Patients with a history of bronchiectasis, cystic fibrosis, lung cancer and interstitial lung disease. 5. Pneumonia or congestive heart failure or suspected malignancy on chest x-ray (CXR) prior to randomisation 6. Patients with a history of infection, or suspected current infection, with mycobacteria tuberculosis, non-tuberculous mycobacteria, or fungal infection 7. Patients not able to perform an FEV1 assessment 8. Patients with known adverse reaction or intolerance to systemic steroids or TNF-alpha antagonists 9. Patients with a history of multiple sclerosis or demyelinating disease (etanercept is contraindicated in these patients) 10. Inability to provide informed consent or comply with the study protocol due to cognitive impairment, language barrier, or distance greater than 100 kilometres from the study centre 11. Patients with a history of human immunodeficiency virus (HIV) or other immuno-compromising diseases 12. Patients with a known malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that was treated with no evidence of recurrence) 13. Patients who have serum white blood cell (WBC) count less than 3,000 or platelet count less than 100,000 at time of randomisation 14. Patients who are pregnant or nursing will be excluded. Females of child-bearing age will be required to have a negative serum or urine pregnancy test before randomisation. 15. Patients with suspected sepsis, i.e., those with temperature greater than 38.5°C or serum WBC greater than 20,000 will be excluded 16. Patients who have a history or active infection with viral hepatitis B or hepatitis C |
| Date of first enrolment | 01/11/2008 |
| Date of final enrolment | 01/01/2011 |
Locations
Countries of recruitment
- Canada
Study participating centre
Ottawa Hospital
Ottawa
K1H 8L6
Canada
K1H 8L6
Canada
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/02/2013 | 20/02/2019 | Yes | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
20/02/2019: Publication reference added.
