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

• ClinicalTrials.gov Identifier: NCT00930982
• Recruitment Status: Completed
• First Posted: July 2, 2009
• Results First Posted: January 30, 2012
• Last Update Posted: December 12, 2014
• Sponsor: Bayer
• Collaborator: Novartis
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bronchiectasis	Drug: Ciprofloxacin (Cipro, BAYQ3939); Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: June 2009
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ciprofloxacin Inhale (BAYQ3939); 32.5 mg ciprofloxacin hydrated corresponding to 50 mg Ciprofloxacin PulmoSphere Inhalation Powder twice daily	Drug: Ciprofloxacin (Cipro, BAYQ3939); Inhalation of 32,5mg Ciprofloxacin inhaled twice a day
Placebo Comparator: Placebo; Inhalation of matching placebo twice a day	Drug: Placebo; Inhalation of matching placebo twice a day

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29). [ Time Frame: Baseline and 29 days ]
   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

Secondary Outcome Measures :

1. Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline and up to end of study (planned at Day 84) ]
   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).
2. Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline and up to end of study (planned at Day 84) ]
   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).
3. Time to Exacerbation With Antibiotic Intervention [ Time Frame: Up to end of study (planned at Day 84) ]
   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.
4. Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by the Saint George's Respiratory Questionnaire (SGRQ), Total Score [ Time Frame: Up to end of study (planned at Day 84) ]
   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.
5. Effect of Ciprofloxacin Inhale Treatment on Health-related Quality of Life (HRQoL) as Measured by Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) [ Time Frame: Up to end of study (planned at Day 84) ]
   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.
6. Change From Baseline in High Sensitive C-reactive Protein (hsCRP) [ Time Frame: Baseline and up to Day 42 ]
   High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.
7. Change From Baseline in Absolute Neutrophil Count (ANC) [ Time Frame: Baseline and up to Day 42 ]
   Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.
8. 24-hour Sputum Volume [ Time Frame: Up to end of study (planned at Day 84) ]
   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.
9. 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) [ Time Frame: Up to end of study (planned at Day 84) ]
   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.
10. Microbiological Response of Cipro Inhale Per Participant [ Time Frame: Up to end of study (planned at Day 84) ]
    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.
11. Microbiological Response of Cipro Inhale Per Pathogen [ Time Frame: Up to end of study (planned at Day 84) ]
    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
12. Emergence of New Potential Respiratory Pathogens [ Time Frame: Up to end of study (planned at Day 84) ]
    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).
13. Emergence of Resistance Among Baseline Pathogens [ Time Frame: Up to end of study (planned at Day 84) ]
    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.

Other Outcome Measures:

1. Change From Baseline in Total Bacterial Load in the Sputum [ Time Frame: Baseline and up to end of study (planned at Day 84) ]
   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 on Day 8. Imputation method: last observation carried forward (LOCF). CFU: colony forming units, log10: decadic logarithm

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arkansas

Little Rock, Arkansas, United States, 72205

United States, California

La Jolla, California, United States, 92037

United States, Colorado

Denver, Colorado, United States, 80206

United States, Connecticut

Farmington, Connecticut, United States, 06030

United States, District of Columbia

Washington, District of Columbia, United States, 20007-2197

United States, Florida

Naples, Florida, United States, 34109-0446

United States, Indiana

Michigan City, Indiana, United States, 46360

United States, New York

Mineola, New York, United States, 11501

United States, Texas

Houston, Texas, United States, 77204

Tyler, Texas, United States, 75708-3154

United States, Utah

Payson, Utah, United States, 84651

Australia, New South Wales

Concord, New South Wales, Australia, 2139

Australia, Queensland

South Brisbane, Queensland, Australia, 4101

Woollongabba, Queensland, Australia, 4102

Australia, South Australia

Adelaide, South Australia, Australia, 5000

Adelaide, South Australia, Australia, 5065

Australia, Victoria

Heidelberg, Victoria, Australia, 3084

Prahran, Victoria, Australia, 3181

Australia, Western Australia

Nedlands, Western Australia, Australia, 6009

Germany

Löwenstein, Baden-Württemberg, Germany, 74245

Rüdersdorf, Brandenburg, Germany, 15562

Frankfurt, Hessen, Germany, 60596

Gelnhausen, Hessen, Germany, 63571

Hannover, Niedersachsen, Germany, 30167

Hannover, Niedersachsen, Germany, 30625

Witten, Nordrhein-Westfalen, Germany, 58452

Koblenz, Rheinland-Pfalz, Germany, 56068

Mainz, Rheinland-Pfalz, Germany, 55131

Geesthacht, Schleswig-Holstein, Germany, 21502

Großhansdorf, Schleswig-Holstein, Germany, 22927

Bad Berka, Thüringen, Germany, 99437

Berlin, Germany, 10961

Berlin, Germany, 12203

Berlin, Germany, 13507

Berlin, Germany, 14059

Spain

Santiago de Compostela, A Coruña, Spain, 15706

Palma de Mallorca, Illes Baleares, Spain, 07010

Badajoz, Spain, 06080

Barcelona, Spain, 08036

Sweden

Uppsala, Sweden, 751 85

United Kingdom

Bristol, Avon, United Kingdom, BS2 8HW

Cambridge, Cambridgeshire, United Kingdom, CB3 8RE

Liverpool, Merseyside, United Kingdom, L9 7JU

Belfast, North Ireland, United Kingdom, BT12 7AB

Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN

Edinburgh, United Kingdom, EH16 4SA

Norwich, United Kingdom, NR4 7UY

Sponsors and Collaborators

Bayer

Novartis

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here and search for Bayer products information provided by EMA 

Publications of Results:

Wilson R, Welte T, Polverino E, De Soyza A, Greville H, O'Donnell A, Alder J, Reimnitz P, Hampel B. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J. 2013 May;41(5):1107-15. doi: 10.1183/09031936.00071312. Epub 2012 Sep 27.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00930982
• Other Study ID Numbers: 12965; 2009-009869-34 ( EudraCT Number )
• First Posted: July 2, 2009
• Results First Posted: January 30, 2012
• Last Update Posted: December 12, 2014
• Last Verified: November 2014

Keywords provided by Bayer:

Ciprofloxacin; Airway infection; Bronchiectasis

Additional relevant MeSH terms:

Bronchiectasis; Bronchial Diseases; Respiratory Tract Diseases; Ciprofloxacin; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors