Targeted AntiBiotics for Chronic Pulmonary Diseases

Phase 4TerminatedNCT03262142

Chronic Obstructive Pulmonary Disease Trial Network, Denmark51 enrolled

Overview

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. non-CF bronchiectasis (BE) and asthma.

P. aeruginosa represents a potentially significant cause of acute exacerbation of chronic pulmonary diseases and is possibly associated with significant morbidity and mortality. Despite this, the role of P. aeruginosa in the course of COPD, non-CF BE and asthma is less well characterized, and evidence based guidelines for management and treatment of the bacteria are lacking. P. 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 chronic pulmonary disease. 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 in patients with COPD, non-CF BE and asthma. 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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Conditions

COPD Respiratory Tract Infections Pseudomonas Aeruginosa Bronchiectasis Asthma

Interventions

Piperacillin/tazobactamDRUG

Intravenous Piperacillin/tazobactam four times daily

CiprofloxacinDRUG

Oral Ciprofloxacin twice daily

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * P. aeruginosa-positive lower respiratory tract sample. * COPD, non-CF bronchiectasis, or asthma verified by a respiratory specialist based on clinical assessment and additional tests: COPD: spirometry; Asthma: reversibility; Non-CF bronchiectasis: high-resolution computed tomography scan. * Minimum of two previous exacerbations, or one previous hospitalization-requiring or emergency room-demanding exacerbation, with the treatment of systemic prednisolone and/or antibiotics within the last 12 months. * Written informed consent Exclusion Criteria: * Immune-modulating therapy (except ≤ 10 mg prednisolone/day) * Men \< 40 years * Women \<= 55 years * Non- menopausal women \> 55 years * Life expectancy \< 90 days * Severe mental illness * Severe language difficulties or inability to provide informed consent * Known drug allergy to 1) Fluoroquinolones and 2) both Piperacillin/tazobactam, Cephalosporins and Carbapenems * Attempted eradication of P. aeruginosa x 2 within the last 12months, or completed eradication therapy within the last 14 days * 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.

Locations (1)

Herlev and Gentofte Hospital

Hellerup, Copenhagen, Denmark

Outcomes

Primary Outcomes

Time to prednisolone and/or antibiotic requiring exacerbation or death, in primary or secondary health care sectors from day 20 to day 365 from randomization.

Time alive and without exacerbation between day 20-365 from the date of recruitment.

Time frame: day 20-365

Days alive and without hospitalisation from day 20 to day 365 from randomization.

Days alive and out of hospital between day 20-365 from the date of recruitment.

Time frame: day 20-365

Secondary Outcomes

Number of re-admissions with pulmonary exacerbation within 365 days from randomization.

Time frame: 365 days

Death within 365 days from randomization.

Time frame: 365 days

Microbiological cure

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.

Time frame: 90 days

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.

Time frame: 14 days

Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.

Data from ClinicalTrials.gov

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