COPD ExacerbationPhase 2/3NCT00789997
TNF-alpha Antagonists for AECOPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
A Phase 2/3 study testing Prednisone, Etanercept and levofloxacin in people with COPD Exacerbation, run by Ottawa Hospital Research Institute.
Trial summary
The purpose of this study is to determine whether treatment with antibiotics plus a TNFalpha antagonist will provide more effective treatment for acute COPD exacerbation compared to the current standard treatment of antibiotics plus prednisone. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- COPD Exacerbation
- What is being tested?
- Prednisone, Etanercept and levofloxacin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- No sites listed yet
- Study dates
- Nov 2008to Oct 2011
- Phase
- Phase 2/3
- 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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Both inpatients and outpatients with acute COPD exacerbation will be selected for randomization. Patients will be considered to fulfill the diagnosis of AECOPD if they meet the following 5 criteria:
- Patients must have had a previous diagnosis of chronic bronchitis, emphysema or COPD established by a physician.
- Patients must have evidence of airflow obstruction on presentation, defined as an forced expiratory volume at one second (FEV1) equal to or less than 70% of predicted and a FEV1 / forced vital capacity (FVC) ratio less 70%.
- Patients must be > 35 years old.
- Patients must have a minimum history of 10 pack years smoking.
- 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:
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- increased chronic baseline dyspnea,
- increased sputum volume or increased sputum purulence
- The above complaints had to have necessitated the emergency department or physician visit.
Who cannot join
- Respiratory failure necessitating admission to an intensive care unit or necessitating use of mechanical invasive or non-invasive (BIPAP) mechanical ventilation.
- Physician diagnosed asthma.
- 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 randomization. (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 randomize patients prior to initial ED treatment we will allow randomization of patients who have been given a single dose of steroid in the ED).
- History of chronic lung disease other than COPD. Patients with a history of bronchiectasis, cystic fibrosis, lung cancer and interstitial lung disease.
- Pneumonia or congestive heart failure or suspected malignancy on chest x-ray (CXR) prior to randomization.
- Patients with a history of infection, or suspected current infection, with mycobacteria tuberculosis, non-tuberculous mycobacteria, or fungal infection.
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- Patients not able to perform an FEV1 assessment.
- Patients with known adverse reaction or intolerance to systemic steroids or TNF-alpha antagonists.
- Patients with a history of multiple sclerosis or demyelinating disease (etanercept is contraindicated in these patients).
- Inability to provide informed consent or comply with the study protocol due to cognitive impairment, language barrier, or distance > 100 kilometres from the study centre.
- Patients with a history of HIV or other immuno-compromising diseases.
- 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).
- Patients who have serum white blood cell count (WBC) < 3,000 or platelet count < 100,000 at time of randomization.
- 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 randomization.
- Patients with suspected sepsis- ie. those with temperature > 38.5 degrees or serum WBC> 20 000 will be excluded.
- Patients who have a history or active infection with viral Hepatitis B or Hepatitis C.
About this study
Official title: TNF-alpha Antagonists for Acute Exacerbations of COPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
The purpose of this study is to determine whether treatment with antibiotics plus a TNFalpha antagonist will provide more effective treatment for acute COPD exacerbation compared to the current standard treatment of antibiotics plus prednisone.
Read the detailed description
Acute exacerbations of COPD (AECOPD)are usually treated with steroids and antibiotics. Currently this conventional therapy has significant side effects including osteoporosis, cataracts,and suppression of the immune system. Studies have suggested that up to 24% of inpatients and 27% of outpatients fail this treatment by 4 weeks. During an acute exacerbation of COPD, the inflammatory process increases. Studies have shown the TNF-alpha cytokines appears to play a major role. Etanercept is a TNF alpha inhibitor. It inactivates TNF alpha cytokines by blocking their interaction with their cellular receptors. This study will compare the treatment of acute exacerbations of COPD with: 1) Levofloxacin 750 mg daily for 10 days + prednisone 40 mg daily for 10 days, or 2) Levofloxacin 750 mg daily for 10 days + etanercept 50 mg subcutaneous given on the day of randomization and one week later. Patients randomized to group 1 (the control group) will receive placebo subcutaneous injections, and patients randomized to group 2 (the experimental group) will receive placebo prednisone capsules.
- Conditions
- COPD Exacerbation
- Being tested
- Prednisone, Etanercept, levofloxacin
- Keywords
- COPD Exacerbation, Etanercept, TNF alpha, Randomized
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
prednisone 40 mg daily for 10 days or placebo prednisone
EtanerceptDrug
Also called Enbrel
etanercept 50 mg subcutaneous given on the day of randomization and one week later or placebo subcutaneous injection
levofloxacinDrug
Also called levaquin
Levofloxacin 750 mg daily for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Etanercept | Experimental | etanercept 50 mg subcutaneous given on the day of randomization and one week later prednisone placebo po daily for 10 days Levofloxacin 750 mg po daily for 10 days. Receives: Drug: Etanercept; Drug: levofloxacin |
| Prednisone | Active comparator | prednisone 40 mg daily for 10 days etanercept placebo subcutaneous given on the day of randomization and one week later Levofloxacin 750 mg daily for 10 days. Receives: Drug: Prednisone; Drug: levofloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Lung Function (Forced Expiratory Volume in 1 Second (FEV1)
FEV1 was obtained using calibrated spirometers at approximately the same time of day at all visits throughout the study. The highest acceptable FEV1 and the highest FVC measurement each obtained on any of three blows (even if not from the same curve) meeting the American Thoracic Society criteria constituted the data for that test set.
Not all participants had Day 14 FEV1 measures collected
Measured: Day 0 to Day 14
Secondary outcomes (1)
Number of Participants With Treatment Failure by 90 Days Assignment
In the etanercept group 16/40 (40%) failed treatment compared with 12/38 (32%) in the prednisone group.
Measured: Day 0 to Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionAug 2011
- Study completionOct 2011
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 COPD ExacerbationStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shawn Aaron, MD, MSc, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00789997
- Sponsor's protocol ID
- 2007791-01H
- Status last verified
- Aug 2013
- First submitted
- 12 Nov 2008
- Last updated
- 11 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Aaron SD, Vandemheen KL, Maltais F, Field SK, Sin DD, Bourbeau J, Marciniuk DD, FitzGerald JM, Nair P, Mallick R. TNFalpha antagonists for acute exacerbations of COPD: a randomised double-blind controlled trial. Thorax. 2013 Feb;68(2):142-8. doi: 10.1136/thoraxjnl-2012-202432. Epub 2012 Nov 17.
PubMed 23161645
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TNF-alpha Antagonists for Acute Exacerbations of COPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT00789997
- Acronym / sponsor ID
- 2007791-01H
- Conditions
- COPD Exacerbation
- Keywords
- COPD Exacerbation, Etanercept, TNF alpha, Randomized
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Aug 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 13 Nov 2008 (estimated)
- Results
- Posted 11 Apr 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 study is to determine whether treatment with antibiotics plus a TNFalpha antagonist will provide more effective treatment for acute COPD exacerbation compared to the current standard treatment of antibiotics plus prednisone.
Detailed description
Acute exacerbations of COPD (AECOPD)are usually treated with steroids and antibiotics. Currently this conventional therapy has significant side effects including osteoporosis, cataracts,and suppression of the immune system. Studies have suggested that up to 24% of inpatients and 27% of outpatients fail this treatment by 4 weeks. During an acute exacerbation of COPD, the inflammatory process increases. Studies have shown the TNF-alpha cytokines appears to play a major role. Etanercept is a TNF alpha inhibitor. It inactivates TNF alpha cytokines by blocking their interaction with their cellular receptors. This study will compare the treatment of acute exacerbations of COPD with: 1) Levofloxacin 750 mg daily for 10 days + prednisone 40 mg daily for 10 days, or 2) Levofloxacin 750 mg daily for 10 days + etanercept 50 mg subcutaneous given on the day of randomization and one week later. Patients randomized to group 1 (the control group) will receive placebo subcutaneous injections, and patients randomized to group 2 (the experimental group) will receive placebo prednisone capsules.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etanercept | Experimental | Drug: Etanercept, Drug: levofloxacinetanercept 50 mg subcutaneous given on the day of randomization and one week later prednisone placebo po daily for 10 days Levofloxacin 750 mg po daily for 10 days. |
| Prednisone | Active comparator | Drug: Prednisone, Drug: levofloxacinprednisone 40 mg daily for 10 days etanercept placebo subcutaneous given on the day of randomization and one week later Levofloxacin 750 mg daily for 10 days. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Both inpatients and outpatients with acute COPD exacerbation will be selected for randomization. Patients will be considered to fulfill the diagnosis of AECOPD if they meet the following 5 criteria:
- Patients must have had a previous diagnosis of chronic bronchitis, emphysema or COPD established by a physician.
- Patients must have evidence of airflow obstruction on presentation, defined as an forced expiratory volume at one second (FEV1) equal to or less than 70% of predicted and a FEV1 / forced vital capacity (FVC) ratio less 70%.
- Patients must be > 35 years old.
- Patients must have a minimum history of 10 pack years smoking.
Key exclusion criteria (16 listed)
- Respiratory failure necessitating admission to an intensive care unit or necessitating use of mechanical invasive or non-invasive (BIPAP) mechanical ventilation.
- Physician diagnosed asthma.
- 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 randomization. (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 randomize patients prior to initial ED treatment we will allow randomization of patients who have been given a single dose of steroid in the ED).
- History of chronic lung disease other than COPD. Patients with a history of bronchiectasis, cystic fibrosis, lung cancer and interstitial lung disease.
- Pneumonia or congestive heart failure or suspected malignancy on chest x-ray (CXR) prior to randomization.
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 |
|---|---|---|
| Prednisoneprednisone 40 mg daily for 10 days or placebo prednisone | Drug | Prednisone |
| EtanerceptAlso: Enbreletanercept 50 mg subcutaneous given on the day of randomization and one week later or placebo subcutaneous injection | Drug | Etanercept |
| levofloxacinAlso: levaquinLevofloxacin 750 mg daily for 10 days. | Drug | Etanercept, Prednisone |
Primary outcome
Change in Lung Function (Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Day 0 to Day 14
FEV1 was obtained using calibrated spirometers at approximately the same time of day at all visits throughout the study. The highest acceptable FEV1 and the highest FVC measurement each obtained on any of three blows (even if not from the same curve) meeting the American Thoracic Society criteria constituted the data for that test set. Not all participants had Day 14 FEV1 measures collected
1 secondary outcome
Number of Participants With Treatment Failure by 90 Days Assignment
Time frame: Day 0 to Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23161645Aaron SD, Vandemheen KL, Maltais F, Field SK, Sin DD, Bourbeau J, Marciniuk DD, FitzGerald JM, Nair P, Mallick R. TNFalpha antagonists for acute exacerbations of COPD: a randomised double-blind controlled trial. Thorax. 2013 Feb;68(2):142-8. doi: 10.1136/thoraxjnl-2012-202432. Epub 2012 Nov 17.
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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.
Shawn Aaron, MD, MSc principal investigator
Ottawa Hospital Research Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Prednisone, Etanercept and levofloxacin in people with COPD Exacerbation, run by Ottawa Hospital Research Institute.
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 9 inclusion and 16 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: finished, as of the sponsor's last update on 11 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Apr 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 in Lung Function (Forced Expiratory Volume in 1 Second (FEV1) (time frame: Day 0 to Day 14). 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 NCT00789997, 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 11 Apr 2016.