Targeted AntiBiotics for Chronic Pulmonary Diseases

NCT03262142 | Terminated Phase 4 DMC

• 1 other identifier: coptrin2
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

chronic pulmonary disease; Pseudomonas Aeruginosa

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  day 20-365

Secondary Outcomes (9)

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

  365 days

• Death within 365 days from randomization.

  365 days

• Microbiological cure

  90 days

• Clinical cure

  14 days

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

  90 days

Study Arms (2)

Standard antibiotic treatment

ACTIVE COMPARATOR

Intravenous Piperacillin/tazobactam + oral Ciprofloxacin for 14 days

Drug: Piperacillin/tazobactam; Drug: Ciprofloxacin

Antibiotic-free treatment

NO INTERVENTION

No antibiotic treatment

Interventions

Piperacillin/tazobactam DRUG

Intravenous Piperacillin/tazobactam four times daily

Standard antibiotic treatment

Ciprofloxacin DRUG

Oral Ciprofloxacin twice daily

Standard antibiotic treatment

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chronic Obstructive Pulmonary Disease Trial Network, Denmark: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Herlev and Gentofte Hospital

Hellerup, Copenhagen, 2900, Denmark

Location

Related Publications (4)

• 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.

  PMID: 36167555 BACKGROUND

• Eklof J, Alispahic IA, Armbruster K, Lapperre TS, Browatzki A, Overgaard RH, Harboe ZB, Janner J, Moberg M, Ulrik CS, Andreassen HF, Weinreich UM, Kjaergaard 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. Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial. Respir Res. 2024 Jun 6;25(1):236. doi: 10.1186/s12931-024-02860-9.

  PMID: 38844921 DERIVED

• 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.

  PMID: 35124256 DERIVED

• 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.

  PMID: 31238116 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Pseudomonas Infections; Bronchiectasis; Asthma

Interventions

Piperacillin, Tazobactam Drug Combination; Ciprofloxacin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Jens-Ulrik Jensen, MD, Consultant, Phd

  Chronic Obstructive Pulmonary Disease Trial Network, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 25, 2017
• Study Start: January 10, 2018
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: May 25, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)