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 number	NCT00789997
Secondary identifying numbers	2007791-01H; 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

Ottawa Hospital
501 Smyth Road
Ottawa
K1H 8L6
Canada

Email	saaron@ohri.ca

Study information

Study design	Multicentre placebo-controlled randomised trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient 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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Etanercept, levofloxacin, prednisone
Primary outcome measure	Change in lung function (FEV1) from day 0 to day 14
Secondary outcome measures	1. Time to treatment failure assessed within a 90 day period 2. Disease specific quality of life, measured at day 0, day 14, day 90 3. Improvement in subjective dyspnoea score, measured at day 0, day 14, day 90 4. Safety: incidence of short- and long-term adverse events from day 0 to day 90
Overall study start date	01/11/2008
Completion date	01/01/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	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

Sponsor information

Ottawa Hospital Research Institute (OHRI) (Canada)
Hospital/treatment centre

725 Parkdale Avenue
Ottawa
K1Y 4E9
Canada

Email	saaron@ohri.ca
Website	http://www.ohri.ca/
"ROR"	https://ror.org/03c62dg59

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-90167)
Government organisation / National government

Alternative name(s): Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
Location: Canada

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
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

Editorial Notes

20/02/2019: Publication reference added.