Clinical trial NCT03262142: Targeted AntiBiotics for Chronic Pulmonary Diseases
Official title: Targeted AntiBiotics for Chronic Pulmonary Disease: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: COPD
Respiratory Tract Infections
Pseudomonas Aeruginosa
Bronchiectasis
Asthma
Keywords: chronic pulmonary disease
Pseudomonas Aeruginosa
Lead sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Sponsor class: OTHER
Collaborators: name: Center for Genomic Medicine, Rigshospitalet, Denmark
First posted: 2017-08-25
Enrollment: 51
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: day 20-365
measure: Days alive and without hospitalisation from day 20 to day 365 from randomization.
timeFrame: day 20-365
Secondary outcomes:
measure: Number of re-admissions with pulmonary exacerbation within 365 days from randomization.
timeFrame: 365 days
measure: Death within 365 days from randomization.
timeFrame: 365 days
measure: Microbiological cure
timeFrame: 90 days
measure: Clinical cure
timeFrame: 14 days
measure: Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.
timeFrame: 90 days
measure: Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.
timeFrame: 90 days
measure: Decrease of ≥ 200 ml in FEV1 from randomization to day 365.
timeFrame: 365 days
measure: Change in COPD Assessment Test (CAT) from randomization to day 90.
timeFrame: 90 days
measure: Change in body mass index (BMI) from randomization to day 90.
timeFrame: 90 days
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Herlev and Gentofte Hospital
state: Copenhagen
Study officials:
affiliation: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
name: Jens-Ulrik Jensen, MD, Consultant, Phd
role: STUDY_DIRECTOR
References:
citation: Eklof J, Alispahic IA, Sivapalan P, Wilcke T, Seersholm N, Armbruster K, Kjaergaard 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, Ostergaard C, Ghathian KSA, Gundersen L, Christensen CW, Bangsborg J, Jensen TT, Sorensen VM, Ellingsgaard T, Datcu R, Coia JE, Bodtger U, Jensen JUS. 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. Trials. 2022 Sep 27;23(1):817. doi: 10.1186/s13063-022-06720-z.
citation: Eklof 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. Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease. Clin Microbiol Infect. 2022 Jul;28(7):990-995. doi: 10.1016/j.cmi.2022.01.017. Epub 2022 Feb 3.
citation: Eklof J, Sorensen 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. Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients. Clin Microbiol Infect. 2020 Feb;26(2):227-234. doi: 10.1016/j.cmi.2019.06.011. Epub 2019 Jun 22.