Targeted Retreatment of COPD Exacerbations

Study Overview
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Brief Summary
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This study investigates the effects of targeted re-treatment of patients who do not recover from an exacerbation of COPD. Half of the patients will receive ciprofloxacin while the other half will receive a placebo.

Detailed Description
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COPD is a long term lung condition where patients suffer recurrent symptom flare-ups, called 'exacerbations'. Patients who have lots of exacerbations have a worse quality of life, poorer ability to breath, and may die earlier than those who don't. Previous research by our group has shown that patients who have an exacerbation and have not completely recovered two weeks after the start of treatment are more likely to suffer another one early than those who completely recover. This study aims to test whether we can prevent this early re-exacerbation by giving an extra course of antibiotics, compared to a placebo. Patients who experience an exacerbation of COPD and are treated with antibiotics will, two weeks after the start of their treatment, be invited to attend a screening visit. Patients will be eligible for the study if they have not fully recovered at this visit (i.e. if they either still have symptoms or if blood tests show there is still inflammation present) and fulfil other diagnostic measures for COPD. Patients will be allocated to the treatment groups at random, and if eligible will be treated with a further 1 week of ciprofloxacin 500mg twice daily or a placebo. Patients will then be followed up in the study for a further 3 months, and the primary study outcome will be the time to the next exacerbation.

Official Title
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Targeted Retreatment of Incompletely Recovered COPD Exacerbations With Ciprofloxacin: a Double-blind, Randomised, Placebo-controlled, Multicentre Phase III Trial

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Ciprofloxacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD confirmed spirometrically at screening COPD exacerbation with treatment commenced 14 days prior to study enrolment and treated with 5-14 days of a non-quinolone antibiotic. Exacerbation here will be defined as an episode of symptomatic worsening of COPD that was treated by the patient's attending clinician. Confirmation of the initial exacerbation diagnosis will be provided from the case notes, referral letter, or directly from the treating clinician, and will be documented in the CRF. Age: ≥ 45 years of age at screening. Persistent symptoms and/or a CRP≥8mg/L when assessed 2 weeks after exacerbation onset Able to complete questionnaires for health status and symptoms and keep written diary cards Severity of disease: Patients with a measured FEV1<80% of predicted normal values at 2 weeks post exacerbation Able and willing to give signed and dated written informed consent to participate. Exclusion Criteria: Other clinically predominant chronic respiratory disease. Intubated and receiving mechanical ventilation Patients with known hypersensitivity to the antibiotic under evaluation, to other quinolones or any excipients of the IMP/placebo. Patients with a prior history of tendonopathy or tendon rupture Elderly patients taking long term systemic corticosteroids Patients on long term antibiotics for other conditions Patient too unwell for randomisation, i.e. requiring retreatment in the judgment of the study doctor Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding. Patient taking clinically significant contraindicated medication as per the SmPC s, such as use of concomitant tizanidine or methotrexate.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ciprofloxacin<br>500 mg, twice daily for 1 week (oral). | Drug: Ciprofloxacin<br>* 500 mg, twice daily for 1 week (oral)<br>|
| Placebo Comparator: Placebo<br>one capsule, twice daily for 1 week. | Drug: Placebo<br>* One capsule, twice daily for 1 week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the Next COPD Exacerbation | The primary outcome will be the time to the next COPD exacerbation following targeted retreatment with the IMP or placebo, censored at 90 days. | Up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of the Initial Exacerbation | Secondary endpoints will include duration of the initial exacerbation following targeted retreatment with the IMP or placebo. | Up to 90 days | 
| Number of Participants With Serious Non Fatal Adverse Events | Secondary endpoints will include adverse events following targeted retreatment with the IMP or placebo. | 7 days of treatment | 
| Changes in Lung Function | Secondary endpoints will include changes from randomization to 90 days in FEV1. | Baseline and 90 days | 
| Number of Participants Who Have Resistance Bacteria in the Sputum | Bacterial load and resistance Secondary endpoints will include resistance following targeted retreatment with the IMP or placebo. | Up to 90 days | 
| Hospital Readmission | Secondary endpoints will include hospital readmission following targeted retreatment with the IMP or placebo. | 90 days of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease (COPD)