Evaluation of Cipro Inhale in Patients With Non-cystic Fibrosis Bronchiectasis

Study Overview
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Brief Summary
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The purpose of this study is to find out if bacterial load in the airways can be reduced after inhalation of ciprofloxacin for 28 days.

Detailed Description
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Safety issues are addressed in the AE section. There is no standardised and unanimously accepted definition of exacerbation in COPD; 4 definitions are widely used: (1) using a combination of 3 cardinal symptoms: increased dyspnea, sputum volume, and sputum purulence; (2) looking at the presence of the following patterns of symptoms during >=2 consecutive days: either 2 or more of 3 major symptoms (increase in dyspnoea, sputum volume and sputum purulence); or any 1 major symptom together with any 1 minor symptom (increase in nasal discharge, wheeze, sore throat, cough or fever); (3) a sustained worsening of the patient's condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD; (4) a complex of respiratory events (i.e. cough, wheezing, dyspnoea or sputum production) lasting >=3 days.

Official Title
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Randomized, Placebo-controlled, Double-blind, Multi-center Study to Evaluate the Safety and Efficacy of Ciprofloxacin Inhale Compared to Placebo in Patients With Non-cystic Fibrosis Bronchiectasis

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: Ciprofloxacin (Cipro, BAYQ3939)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a proven and documented diagnosis of non-cystic fibrosis idiopathic or post pneumonic bronchiectasis Stable pulmonary status and stable regimen of standard treatment at least for the past 30 days Exclusion Criteria: Forced Expiratory Volume 1 < 35% or > 80% Allergic bronchopulmonary aspergillosis Immunodeficiency disease requiring immunoglobulin replacement Inflammatory bowel disease

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciprofloxacin Inhale (BAYQ3939)<br>32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily | Drug: Ciprofloxacin (Cipro, BAYQ3939)<br>* Inhalation of 32,5mg Ciprofloxacin inhaled twice a day<br>|
| Placebo Comparator: Placebo<br>Inhalation of matching placebo twice a day | Drug: Placebo<br>* Inhalation of matching placebo twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29). | Total bacterial load was determined in sputum collected before the inhalation of study drug. Sputum samples were either provided by the participant during the respective study visit, or participants had to bring a sputum sample that had been produced within the 4 hours prior to the visit. Induced sputum samples could be collected if the participant was unable to produce a spontaneously expectorated sputum sample of > 2 mL. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm | Baseline and 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FEV1 was defined as the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS). Imputation method: last observation carried forward (LOCF). | Baseline and up to end of study (planned at Day 84) | 
| Change From Baseline in Forced Vital Capacity (FVC) | Pulmonary function testing (spirometry) was conducted in accordance with American Thoracic Society standards. FVC was defined as the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, i.e. vital capacity performed with a maximally forced expiratory effort expressed in liters at BTPS. Imputation method: last observation carried forward (LOCF). | Baseline and up to end of study (planned at Day 84) | 
| Time to Exacerbation With Antibiotic Intervention | Acute exacerbation was defined according to the joint American Thoracic Society/European Respiratory Society criteria. For detailed information with regard to this definition of acute exacerbation, please refer to the detailed description in the protocol section. The time to an acute exacerbation with antibiotic intervention was determined. | Up to end of study (planned at Day 84) | 
| Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score | Participants completed the Saint George's Respiratory Questionnaire (SGRQ). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges from 0 to 100 with 100 being the worst possible score. | Up to end of study (planned at Day 84) | 
| Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) | Participants completed the Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS). They were assured that all data would be treated confidentially and that the answers would not have any influence on study drug treatment. Participants completed the questionnaires on their own in a quiet area, without discussing them with study staff or accompanying persons (e.g. friends or relatives) and before being seen by the clinician. The score ranges between 1 and 7, 1 being the worst possible score. | Up to end of study (planned at Day 84) | 
| Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available. | Baseline and up to Day 42 | 
| Change From Baseline in Absolute Neutrophil Count (ANC) | Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available. | Baseline and up to Day 42 | 
| 24-hour Sputum Volume | Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. The volume of the completed sample was determined. | Up to end of study (planned at Day 84) | 
| 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) | Participants were asked to start 24-hour sputum collection samples 24 hours before coming for the respective study visit. Sputum color was assessed as either 'clear', or as 'yellow', 'green' or 'rust', or an assessment of 'no sputum' was made. | Up to end of study (planned at Day 84) | 
| Microbiological Response of Cipro Inhale Per Participant | Microbiological response was defined as reduction in bacterial load or eradication (measured as the percentage of participants with positive culture). Missing values were not imputed. | Up to end of study (planned at Day 84) | 
| Microbiological Response of Cipro Inhale Per Pathogen | Microbiological response was defined as reduction in bacterial load or eradication (measured as the number of participants with positive culture). Missing values were not imputed. Pathogens analyzed: Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Serratia marcescens, Pseudomonas aeruginosa, mucoid, Pseudomonas aeruginosa, non mucoid, Stenotrophomonas maltophilia, Achromobacter xylosoxydans, Moraxella catarrhalis, Haemophilus influenzae | Up to end of study (planned at Day 84) | 
| Emergence of New Potential Respiratory Pathogens | The emergence of new potential respiratory pathogens was evaluated using microbiological analysis. Evaluated was the cumulative number of participants with first appearance of new potential respiratory antigens at each time point. In some cases, participants attended the end of study visit later than Day 84 (up to Day 88). | Up to end of study (planned at Day 84) | 
| Emergence of Resistance Among Baseline Pathogens | The emergence of resistance (at least two-fold increase of Minimal inhibitory concentration, MIC, vs. baseline values) probably or possibly related to study medication among baseline pathogens was evaluated using microbiological analysis. | Up to end of study (planned at Day 84) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ciprofloxacin, Airway infection, Bronchiectasis