Targeted AntiBiotics for Chronic Pulmonary Diseases

Asthma Clinical Trial

— Target-ABC  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03262142
• Other study ID #: coptrin2
• Status: Terminated
• Phase: Phase 4
• Start date: January 10, 2018
• Est. completion date: March 1, 2023

Study information

• Verified date: May 2023
• Source: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 51
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Piperacillin/tazobactam
Intravenous Piperacillin/tazobactam four times daily
• Ciprofloxacin
Oral Ciprofloxacin twice daily

Locations

Country	Name	City	State
Denmark	Herlev and Gentofte Hospital	Hellerup	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Chronic Obstructive Pulmonary Disease Trial Network, Denmark	Center for Genomic Medicine, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Number of re-admissions with pulmonary exacerbation within 365 days from randomization.	Number of re-admissions with pulmonary exacerbation within 365 days from randomization.	365 days
Secondary	Death within 365 days from randomization.	Death within 365 days from randomization.	365 days
Secondary	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.	90 days
Secondary	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.	14 days
Secondary	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.	90 days
Secondary	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.	90 days
Secondary	Decrease of = 200 ml in FEV1 from randomization to day 365.	Decrease of = 200 ml in FEV1 from randomization to day 365.	365 days
Secondary	Change in COPD Assessment Test (CAT) from randomization to day 90.	Change in COPD Assessment Test (CAT) from randomization to day 90.	90 days
Secondary	Change in body mass index (BMI) from randomization to day 90.	Change in body mass index (BMI) from randomization to day 90.	90 days

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