Ceftidoren Versus Levofloxacin in the Treatment of Patients With Acute Exacerbations of Chronic Bronchitis (AECB)

Ceftidoren Versus Levofloxacin in the Treatment of Patients With Acute Exacerbations of Chronic Bronchitis (AECB). Multi-centre, Open-label, Randomised, Pilot Study to Evaluate the Effects of the Treatment on Serum Inflammatory Biomarkers

40 outpatients with exacerbations of Chronic Obstructive Pulmonary Diseases (COPD) will be enrolled in a multi-centre, open-label, randomised, pilot study. Two treatments will be compared, ceftidoren 200 mg bid for 5 days and levofloxacin 500 mg once daily for 7 days. Primary objective of the study is to evaluate the effects of the treatment on serum inflammatory biomarkers and the secondary objective is to evaluate the clinical and microbiological efficacy at the Test Of Cure visit (TOC), DAY 7-10 (end of treatment).

The study foresees 4 visits: Visit 1 (enrolment, day 1 of treatment); Visit 2 (day 2-4); Visit 3 (Test Of Cure-TOC visit, day 7-10 end of treatment), Visit 3 (Late Post Therapy assessment, Day 28-30).

The primary parameter to test the efficacy of the study medications will be the assessment of the speed of reduction of inflammatory parameters (CRP, PCT and KL6). Every reduction of 10% will be taken into account. The comparison between treatments will be performed at visit 2 and 3.

Study Overview

• Status: Completed
• Conditions: COPD Exacerbation
• Intervention / Treatment: Drug: ceftidoren; Drug: levofloxacin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20122
    • IRCCS Ospedale Maggiore Policlinico via F. Sforza 35

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female outpatients with age between 40 and 75 years with no limitation of race.

2. Patients with a diagnosis of Acute Exacerbations of Chronic Bronchitis* characterized by the presence of the following three symptoms, or at least two including purulence:

   • increased dyspnoea;
   • increased of sputum volume;

   • increased of sputum purulence, that had to be confirmed macroscopically by the investigator.

     • Chronic bronchitis is characterized by cough and excessive secretion of mucus and is diagnosed when patients report production of sputum on most days over at least three consecutive months for 2 or more consecutive years (American Thoracic Society 1995).
3. FEV1 >50% of the predicted value.
4. Availability of a valid sputum specimen of broncho-pulmonary origin for microbiological evaluation obtained by either expectoration, suction, bronchoscopy or bronchial lavage. Valid samples will be characterized by < 10 squamous epithelial cells and > 25 polymorph nuclear leucocytes per low-power magnification 100x field (Wilson 2004).
5. Negative chest radiography to rule out pneumonia and active tuberculosis.
6. Written informed consent to the trial signed and dated by the patient according to the local regulations, obtained prior to all activities related to the trial.

Exclusion Criteria:

1. Hypersensitivity or allergy to antibacterial betalactams or fluoroquinolones and/or to any component of the study medications.
2. Underlying asthma.
3. Systemic corticosteroids (treatment since ≤ 2 weeks before trial drug administration) are excluded, unless patients are chronically treated (treatment for >2 weeks before trial drug administration). Corticosteroid nasal spray administration is allowed in the first 3 days of the study drug administrations only.
4. Childbearing potential where pregnancy is not excluded by pregnancy test in urine (HCG), or lactation.
5. History of tendinopathy.
6. Recent or past history of psychiatric illness or epilepsy.
7. Recent or past history of cardiac disease or rhythm disorders or clinically significant ECG abnormalities.
8. Latent or known deficiencies for the glucose-6-phosphate dehydrogenase activity.
9. Known severe hepatic and/or renal insufficiency (AST, ALT and/or creatinine levels more than twice as high as the Upper Laboratory Norm, ULN). Should laboratory data not be available when treatment is required, the patient may be conditionally enrolled.
10. Other lower respiratory tract illness: severe bronchiectasis, cystic fibrosis, or pulmonary malignancy.
11. Concurrent infections and /or neoplasm.
12. Concomitant treatment with hypoglycemic drugs.
13. Patients under treatment with fenbufen and xanthines. Patients treated with xanthines could however be recruited if plasma levels were monitored; if plasma levels exceeded concentrations of 10-15 micrograms/ml, the daily dosages of xanthines should be lowered by the Investigator (Hendels 1983);
14. Treatment with antibiotics or antibacterials within the previous week
15. Treatment with experimental drugs in the previous 4 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ceftidoren; ceftidoren 200 mg bid for 5 days	Drug: ceftidoren; ceftidoren 200 mg bid for 5 days; Other Names: Giasion; J01D
Active Comparator: levofloxacin; levofloxacin 500 mg once daily for 7 days	Drug: levofloxacin; levofloxacin 500 mg once daily for 7 days; Other Names: levoxacin; J01M

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum inflammatory biomarkers	assessment of the speed of reduction of inflammatory parameters (C-reactive protein(CRP), procalcitonin( PCT) and mucin-like glycoprotein(KL6)). Every reduction of 10% will be taken into account.	change from baseline at day 2-4 and day 7-10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical efficacy	Clinical assessment (Vist 2 and visit 3) of signs and symptoms of acute exacerbations of Chronic bronchitis(AECB), such as sputum purulence, sputum volume, dyspnoea, cough and body temperature using a clinical score.The total scores obtained at Visit 2 and Visit 3 test of cure (TOC) will be compared with those obtained at Visit 1.	change from baseline to day 2-4 and day 7-10
Microbiology efficacy	Microbiological assessments will be performed on valid sputum specimens At the TOC Visit, 7-10 days after the end of treatment. The results obtained at Visit 2 and Visit 3 test of cure(TOC) will be compared with those obtained at Visit 1	change from baseline to day 2-4 and day 7-10

Collaborators and Investigators

• Sponsor: University of Milan
• Investigators: Study Chair: Francesco B Blasi, MD, University of Milan Italy

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: September 16, 2011
• First Submitted That Met QC Criteria: November 3, 2011
• First Posted (Estimate): November 8, 2011

Study Record Updates

• Last Update Posted (Estimate): June 5, 2012
• Last Update Submitted That Met QC Criteria: June 2, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: treatment; exacerbations; inflammation; levofloxacin; Chronic bronchitis; ceftidoren
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Bronchitis; Bronchitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin
• Other Study ID Numbers: SP1; 2011-000531-88 (EudraCT Number)