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TerminatedNCT03262142Target-ABCUpdated May 25, 2023

Targeted AntiBiotics for Chronic Pulmonary Diseases

A Phase 4 interventional study of Piperacillin/tazobactam and Ciprofloxacin in COPD, Respiratory Tract Infections and Pseudomonas Aeruginosa, sponsored by Chronic Obstructive Pulmonary Disease Trial Network, Denmark. Terminated at 1 site in Denmark. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2023-05-25.

Sponsored by Chronic Obstructive Pulmonary Disease Trial Network, Denmark · Phase 4, Interventional, and Other

Why this study was terminated
Slow recruitment
Phase
Phase 4
Study type
Interventional
Enrollment
51
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

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

Keywords

  • chronic pulmonary disease
  • Pseudomonas Aeruginosa
03

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 4
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
51 participants (actual)

Study arms

  • Active comparator
    Standard antibiotic treatment

    Intravenous Piperacillin/tazobactam + oral Ciprofloxacin for 14 days

    Drug: Piperacillin/tazobactam · Drug: Ciprofloxacin

  • No intervention
    Antibiotic-free treatment

    No antibiotic treatment

Interventions

  • DrugPiperacillin/tazobactam

    Intravenous Piperacillin/tazobactam four times daily

  • DrugCiprofloxacin

    Oral Ciprofloxacin twice daily

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

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

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

    Time frame: 365 days

  2. Death within 365 days from randomization.

    Death within 365 days from randomization.

    Time frame: 365 days

  3. 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

  4. 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

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

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

    Time frame: 90 days

  6. Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.

    Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.

    Time frame: 90 days

  7. Decrease of ≥ 200 ml in FEV1 from randomization to day 365.

    Decrease of ≥ 200 ml in FEV1 from randomization to day 365.

    Time frame: 365 days

  8. Change in COPD Assessment Test (CAT) from randomization to day 90.

    Change in COPD Assessment Test (CAT) from randomization to day 90.

    Time frame: 90 days

  9. Change in body mass index (BMI) from randomization to day 90.

    Change in body mass index (BMI) from randomization to day 90.

    Time frame: 90 days

06

Study locations

1 site
  • Herlev and Gentofte Hospital
    Hellerup, Copenhagen 2900, Denmark
07

References and documents

Publications

  • 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. PubMed 36167555 ↗
  • 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. PubMed 35124256 ↗
  • 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. PubMed 31238116 ↗

Related links

Individual participant data

Plan to share: Yes

08

Registry details

Key details

Study ID
NCT03262142
Lead sponsor
Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Collaborators
Center for Genomic Medicine, Rigshospitalet, Denmark
Responsible party
Josefin Eklöf (Principal Investigator, Chronic Obstructive Pulmonary Disease Trial Network, Denmark) — Principal investigator
First posted
Aug 25, 2017
Start date
Jan 10, 2018
Primary completion
Mar 1, 2023
Completion
Mar 1, 2023
Last update
May 25, 2023

Study contacts

Jens-Ulrik Jensen, MD, Consultant, Phd
study director · Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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