Targeted AntiBiotics for Chronic Pulmonary Diseases

Conditions

Asthma, Bronchiectasis, COPD, Pseudomonas Aeruginosa, Respiratory Tract Infections

Keywords

chronic pulmonary disease, Pseudomonas Aeruginosa

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. non-CF bronchiectasis (BE) and asthma.

Detailed description

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.

Eklöf J, Alispahic IA, Armbruster K, Lapperre TS, Browatzki A, Overgaard RH, Harboe ZB, Janner J, Moberg M, Ulrik CS, Andreassen HF, Weinreich UM, Kjærgaard JL, Villadsen J, Fenlev CS, Jensen TT, Christensen CW, Bangsborg J, Ostergaard C, Ghathian KSA, Jordan A, Klausen TW, Nielsen TL, Wilcke T, Seersholm N, Sivapalan P, Jensen JS.

2024-06-064 citations

10.1186/s12931-024-02860-9

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

Eklöf J, Alispahic IA, Sivapalan P, Wilcke T, Seersholm N, Armbruster K, Kjærgaard JL, Saeed MI, Nielsen TL, Browatzki A, Overgaard RH, Fenlev CS, Harboe ZB, Andreassen HF, Lapperre TS, Pedersen L, Johnsen S, Ulrik CS, Janner J, Moberg M, Heidemann M, Weinreich UM, Vijdea R, Linde H, Titlestad I, Johansson SL, Rosenvinge FS, Østergaard C, Ghathian KSA, Gundersen L, Christensen CW, Bangsborg J, Jensen TT, Sørensen VM, Ellingsgaard T, Datcu R, Coia JE, Bodtger U, Jensen JUS.

2022-09-273 citations

10.1186/s13063-022-06720-z

Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

Eklöf J, Misiakou MA, Sivapalan P, Armbruster K, Browatzki A, Nielsen TL, Lapperre TS, Andreassen HF, Janner J, Ulrik CS, Gabrielaite M, Johansen HK, Jensen A, Nielsen TV, Hertz FB, Ghathian K, Calum H, Wilcke T, Seersholm N, Jensen JS, Marvig RL.

2022-02-0317 citations

10.1016/j.cmi.2022.01.017

Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with COPD

Josefin Eklöf, Mari-Anna Misiakou, Pradeesh Sivapalan, Karin Armbruster, Andrea Browatzki et al. (21 authors)

2020-09-071 citations

10.1183/13993003.congress-2020.4932

Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients.

Eklöf J, Sørensen R, Ingebrigtsen TS, Sivapalan P, Achir I, Boel JB, Bangsborg J, Ostergaard C, Dessau RB, Jensen US, Browatzki A, Lapperre TS, Janner J, Weinreich UM, Armbruster K, Wilcke T, Seersholm N, Jensen JUS.

2019-06-2296 citations

10.1016/j.cmi.2019.06.011

Interventions

DRUGPiperacillin/tazobactam

Intravenous Piperacillin/tazobactam four times daily

DRUGCiprofloxacin

Oral Ciprofloxacin twice daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
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.	day 20-365	Time alive and without exacerbation between day 20-365 from the date of recruitment.
Days alive and without hospitalisation from day 20 to day 365 from randomization.	day 20-365	Days alive and out of hospital between day 20-365 from the date of recruitment.

Secondary

Measure	Time frame	Description
Microbiological cure	90 days	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	14 days	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 days with non-invasive ventilation or invasive ventilation within 90 days from randomization.	90 days	Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.
Number of re-admissions with pulmonary exacerbation within 365 days from randomization.	365 days	Number of re-admissions with pulmonary exacerbation within 365 days from randomization.
Decrease of ≥ 200 ml in FEV1 from randomization to day 365.	365 days	Decrease of ≥ 200 ml in FEV1 from randomization to day 365.
Change in COPD Assessment Test (CAT) from randomization to day 90.	90 days	Change in COPD Assessment Test (CAT) from randomization to day 90.
Change in body mass index (BMI) from randomization to day 90.	90 days	Change in body mass index (BMI) from randomization to day 90.
Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.	90 days	Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.
Death within 365 days from randomization.	365 days	Death within 365 days from randomization.

Countries

Denmark

Outcome results

None listed