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

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00930982
First received: June 30, 2009
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Bronchiectasis
Drug: Ciprofloxacin (Cipro, BAYQ3939)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Change From Baseline in Total Bacterial Load in the Sputum at End of Treatment (Day 29). [ Time Frame: Baseline and 29 days ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline and up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline and up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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).

  • Time to Exacerbation With Antibiotic Intervention [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in High Sensitive C-reactive Protein (hsCRP) [ Time Frame: Baseline and up to Day 42 ] [ Designated as safety issue: No ]
    High sensitive C-reactive protein (hsCRP) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.

  • Change From Baseline in Absolute Neutrophil Count (ANC) [ Time Frame: Baseline and up to Day 42 ] [ Designated as safety issue: No ]
    Absolute neutrophil count (ANC) was determined from safety blood samples. Missing or invalid values were replaced with the last valid value available.

  • 24-hour Sputum Volume [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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.

  • 24-hour Sputum Color (Percentage of Participants With Non-clear Sputum) [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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.

  • Microbiological Response of Cipro Inhale Per Participant [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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.

  • Microbiological Response of Cipro Inhale Per Pathogen [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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

  • Emergence of New Potential Respiratory Pathogens [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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).

  • Emergence of Resistance Among Baseline Pathogens [ Time Frame: Up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Total Bacterial Load in the Sputum [ Time Frame: Baseline and up to end of study (planned at Day 84) ] [ Designated as safety issue: No ]
    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


Enrollment: 124
Study Start Date: June 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930982

  Show 47 Study Locations
Sponsors and Collaborators
Bayer
Novartis
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00930982     History of Changes
Other Study ID Numbers: 12965, 2009-009869-34
Study First Received: June 30, 2009
Results First Received: September 19, 2011
Last Updated: April 2, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration
Spain: Agencia Espanola del Medicamento y Productos Sanitarios
UK: Medicines and Healthcare products Regulatory Agency_MHRA0
Australia: Department of Health and Ageing, TGA/ Therapeutic Goods Administration
Sweden: Medical Products Agency

Keywords provided by Bayer:
Ciprofloxacin
Airway infection
Bronchiectasis

Additional relevant MeSH terms:
Bronchiectasis
Fibrosis
Bronchial Diseases
Respiratory Tract Diseases
Pathologic Processes
Ciprofloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014