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Slow recruitment
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| Name | Class |
|---|---|
| Rigshospitalet, Denmark | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard antibiotic treatment | Active Comparator | Intravenous Piperacillin/tazobactam + oral Ciprofloxacin for 14 days |
|
| Antibiotic-free treatment | No Intervention | No antibiotic treatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Piperacillin/tazobactam | Drug | Intravenous Piperacillin/tazobactam four times daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Death within 365 days from randomization. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jens-Ulrik Jensen, MD, Consultant, Phd | Chronic Obstructive Pulmonary Disease Trial Network, Denmark | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Herlev and Gentofte Hospital | Hellerup | Copenhagen | 2900 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36167555 | Background | 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. | |
| 38844921 |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D012141 | Respiratory Tract Infections |
| D011552 | Pseudomonas Infections |
| D001987 | Bronchiectasis |
| D001249 | Asthma |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| D002939 | Ciprofloxacin |
| ID | Term |
|---|---|
| D000078142 | Tazobactam |
| D010397 | Penicillanic Acid |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
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| Ciprofloxacin | Drug | Oral Ciprofloxacin twice daily |
|
Death within 365 days from randomization.
| 365 days |
| 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 |
| 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 |
| 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 |
| 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 |
| Decrease of ≥ 200 ml in FEV1 from randomization to day 365. | Decrease of ≥ 200 ml in FEV1 from randomization to day 365. | 365 days |
| Change in COPD Assessment Test (CAT) from randomization to day 90. | Change in COPD Assessment Test (CAT) from randomization to day 90. | 90 days |
| Change in body mass index (BMI) from randomization to day 90. | Change in body mass index (BMI) from randomization to day 90. | 90 days |
| Derived |
| 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. |
| 35124256 | 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. |
| 31238116 | 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. |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007239 | Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D001982 | Bronchial Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007769 |
| Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D010878 | Piperacillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D013457 | Sulfur Compounds |
| D013450 | Sulfones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |