Target-ABC: Targeted AntiBiotics for Chronic Obstructive Pulmonary Disease
Study Details
Study Description
Brief Summary
This is a prospective, randomized multi-center trial investigating the impact of lower airway infection with P. aeruginosa in COPD patients. The aim of the study is to evaluate if targeted antibiotic therapy against P. aeruginosa can improve the prognosis in patients with COPD.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
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aeruginosa represents a potentially significant cause of acute exacerbation of COPD (AECOPD) and is possibly associated with significant morbidity and mortality. Despite this, the role of P. aeruginosa in the course of COPD is less well characterized, and evidence based guidelines for management and treatment of the bacteria are lacking.
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aeruginosa is more likely to be isolated from patients with more advanced disease and severely impaired lung function. It is, however, difficult to draw definitive conclusions regarding the extent to which the bacteria contributes to adverse clinical outcomes since severely reduced lung function by itself is a strong predictor of mortality in patients with COPD. Infection with P. aeruginosa might therefore be secondary to damaged lung tissue and decreased lung function, and thereby have no independent impact on the prognosis
So far, and to the investigators best knowledge, no randomized controlled trial has been conducted to investigate whether specific antibiotic treatment of P. aeruginosa can reduce the risk of new exacerbations and improve the long-term prognosis of COPD patients.
In Denmark, the first choice of treatment for P. aeruginosa is usually a 10-14 day therapy of intravenous combination treatment of P. aeruginosa active antibiotics (piperacillin/tazobactam and ciprofloxacin).
The aim of the study is to investigate whether the intervention with targeted pseudomonas active antibiotics can reduce the loss of lung function, reduce the frequency of exacerbations and mortality.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Standard antibiotic treatment Intravenous Piperacillin/tazobactam + oral Ciprofloxacin for 14 days |
Drug: Piperacillin/tazobactam
Intravenous Piperacillin/tazobactam three times daily
Drug: Ciprofloxacin
Oral Ciprofloxacin twice daily
|
| No Intervention: Antibiotic-free treatment
|
Outcome Measures
Primary Outcome Measures
- Time to systemic corticosteroid and/or antibiotic requiring AECOPD (in both primary or secondary health sector) or death. [The estimated time periode for assessment is 1 year.]
From date of randomization until the date of first documented exacerbation or date of death from any cause, whichever comes first. The study is "event driven" and will close when 67% of the patients in the control group has met an event.
Secondary Outcome Measures
- Alive and without AECOPD [Day 365]
- Death [Within 12 months]
- Microbiological cure [Day 90]
Microbiological cure = P. aeruginosa-negative sputum culture until day 90. Non-microbiological cure = positive sputum culture with same P.aeruginosa clone as baseline clone ≤ day 90. Re-infection = positive sputum culture with different P. aeruginosa clone compare to baseline clone ≤ day 90.
- Clinical cure [Day 14]
Clinical cure = resolution or improvement of clinical symptoms related to P. aeruginosa within day 14. Clinical failure = persistent of worsened clinical symptoms related to P. aeruginosa within day 14.
- Number of re-admissions with AECOPD [Within 12 months]
- Number of days with non-invasive ventilation (NIV) or respiratory therapy [Within 90 days]
- Change in FEV1 [From baseline to 3 months]
- Fall in FEV1 ≥ 200 ml /year [From baseline to day 365]
- Change in COPD Assessment Test (CAT) [From baseline to 3 months]
- Changes in body mass index (BMI) [From baseline to 3 months]
Weight and height will be combined to report BMI in kg/m^2
Eligibility Criteria
Criteria
Inclusion Criteria:
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1 positive sputum sample for P. aeruginosa
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COPD (verified by pulmonologist based on clinical and spirometric criteria)
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Minimum 1 previous AECOPD requiring hospitalization/ emergency department visit and administration of systemic prednisolone +/- antibiotic treatment within the last 12 months
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Completed and signed informed consent
Exclusion Criteria:
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Immune-modulating therapy (except ≤ 10 mg prednisolone/day)
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Men < 40 years
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Women <55 years
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Non- menopausal women > 55 years ¤
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Life expectancy < 90 days
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Severe mental illness
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Severe language difficulties or inability to provide informed consent
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Known drug allergy to 1) Fluoroquinolones or 2) both Piperacillin/tazobactam, Cephalosporins and Carbapenems
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Attempted eradication of P. aeruginosa x 2 within the last 12months, or completed eradication therapy within the last 14 days ¤¤
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The investigator 's opinion is that the participant requires antibiotic treatment. This exclusion criterion must be discussed with the coordinating investigator before the final decision on exclusion is taken
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Has had menstruation within the last 12 months ¤¤ Treatment with same antibiotics as used in the trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Herlev and Gentofte Hospital | Hellerup | Copenhagen | Denmark | 2900 |
| 2 | Nordsjællands Hospital | Hillerød | Denmark |
Sponsors and Collaborators
- Chronic Obstructive Pulmonary Disease Trial Network, Denmark
- Center for Genomic Medicine, Rigshospitalet, Denmark
Investigators
- Study Director: Jens-Ulrik Jensen, MD, Consultant, Phd, Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- coptrin2