Telithromycin in Respiratory Tract Infections

An Open, Multicenter, Non-comparative, Phase IV Trial of Efficacy and Safety of Ketek(Telithromycin) 800mg

Primary Objectives:

• The primary objective of the study is to evaluate clinical efficacy i.e. to show that with respect to clinical cure rate, Ketek® (telithromycin) in the treatment of community acquired respiratory tract infections: community acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis (AECB) and acute sinusitis (AS), in outpatients.

Secondary Objectives:

The secondary objectives are to:

• Further assess the efficacy of Ketek® (telithromycin) by considering the rate at which additional antibacterials were prescribed to treat the primary infection; the rate of hospitalisation due to a complication of the primary infection and assessment of bacteriological data, chest X-ray and sinus X-ray if available.
• Evaluate safety of Ketek® (telithromycin) through Adverse Event (AE) and Serious Adverse Event (SAE) reporting

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections
• Intervention / Treatment: Drug: telithromycin

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

General Conditions

• Outpatients

• Fulfillment of clinical diagnostic criteria for one of the following indications:

  • Mild to moderate Community Acquired Pneumonia (CAP)
  • Acute bacterial Exacerbation of Chronic Bronchitis (AECB)
  • Acute Sinusitis (AS)

For CAP

The Criteria to be fulfilled are:

• New onset of at least two of the following:

  • Cough
  • Production of purulent sputum
  • Auscultatory findings compatible with pneumonia, e.g. rales, evidence of pulmonary consolidation
  • Dyspnea or tachypnea
  • Fever
  • Elevated total white blood cell count > 10 000/mm3 or >15% bands regardless of total count
• Chest X-ray findings supporting a clinical diagnosis of bacterial pneumonia (e.g. new infiltrate)

For AECB

The Criteria to be fulfilled are:

• Chronic bronchitis defined as cough and excessive sputum production for more than 2 consecutive years and on most days in a 3-month consecutive period.

• Exacerbation defined by:

  • Increase in sputum purulence, or
  • Increase in sputum volume, or
  • Increase in dyspnea

For AS

The criteria to be fulfilled are:

At least two of the major or one major and two minor factors listed below, for more than one week and less than 4 weeks:

• Major factors:

  • Facial pressure and/or pain
  • Facial congestion or fullness
  • Nasal obstruction
  • Nasal purulence or postnasal discharge
  • Hyposmia or anosmia
  • Fever

• Minor factors:

  • Headache
  • Halitosis
  • Fatigue
  • Dental pain
  • Cough
  • Ear pain, pressure or fullness

Exclusion Criteria:

General Conditions

Subjects presenting with any of the following will not be included in the study:

• Treatment required during the study with ergot alkaloid derivatives, pimozide, astemizole, terfenadine, cisapride, simvastatin, atorvastatin and lovastatin, and the oral use of the benzodiazepines midazolam, triazolam and alprazolam.
• History of congenital or family history of long QT syndrome (if not excluded by ECG) or known acquired QT interval prolongation.
• Known hypersensitivity to telithromycin or to macrolide antibiotics.
• Hospital acquired infections (hospitalization for more than 72 hours within 7 days of study entry).
• Pregnant or breast-feeding women. For the women of childbearing potential it is left to the investigators discretion to establish a lack of pregnancy, e.g. with contraceptive use, menstrual pattern, urinary pregnancy test.
• Subjects with severely impaired renal function (creatinine clearance <30 ml/min).
• Subjects that had received anti-bacterials for more than 24 hours within 7 days prior to enrollment in the study, unless the treatment has failed.
• Subjects receiving medications, including other anti-microbials or anti-cancer drugs, that could interfere with the evaluation.
• Microbiologically documented infection with a pathogen known prior to inclusion to be resistant to the study medications.
• Infection, other than the primary infection for which the subject is being included in the study that requires use of other systemic anti-bacterial drug.
• Splenectomised subjects.
• Use of Ketek® (telithromycin) or participation in a study using Ketek® (telithromycin) in the previous 30 calendar days.
• Subjects that have received any investigational drug within 4 weeks of enrollment in the study.
• No subject will be allowed to enroll in this study more than once.

For CAP

Additional exclusion criteria are:

• Severe pneumonia defined by any one of the following:

  • Judged as needing Intensive Care Unit admission.
  • Need of parenteral antibiotic treatment (if the attending physician wants to prescribe a parenteral treatment for adherence reasons or local prescription habits this is accepted, provided that the patient does not have a severe pneumonia).
  • Acute respiratory failure or requirement for mechanical ventilation.
  • Altered mental status resulting from the infective process.
  • Resting respiratory rate > 30 breaths/min.
  • Chest X-ray showing increase in opacity by > 50% within 48 hours of current evaluation.
• Total white blood cell count < 4 000/mm3.
• Aspiration pneumonia.
• Pneumonia suspected to be non-bacterial (due to fungus or viral).
• Subjects suffering from severe bronchiectasis (production of more than 125 mL of sputum/day), cystic fibrosis, active tuberculosis, pulmonary infarction or embolism, bronchial obstruction, lung cancer or lung metastasis, lung abscess, extra-pulmonary extension (like meningitis, septic arthritis, endocarditis).

For AECB

Additional exclusion criteria are:

• Need of parenteral antibiotic treatment (if the attending physician wants to prescribe a parenteral treatment for adherence reasons or local prescription habits this is accepted, provided that the patient does not have a severe infection).
• Acute respiratory failure (respiratory distress, hypercarbia, worsening hypoxemia) or requirement for mechanical ventilation.
• Severe bronchiectasis, cystic fibrosis, active tuberculosis, pulmonary infarction or embolism, bronchial obstruction, lung cancer or lung metastasis, lung abscess.

For AS

Additional exclusion criteria are:

• Need of immediate surgery for the treatment of AS.
• Chronic sinusitis (symptoms lasting more than 4 weeks).
• Recurrent sinusitis (4 or more episodes of sinusitis requiring antibiotic therapy in the previous 12 months).
• Nosocomial acquired sinusitis.
• Cystic fibrosis, immotile cilia syndrome.
• Obstructive lesions in nasopharynx (e.g. polyps, tumor).
• Use of nasal, nasogastric or nasotracheal catheters.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical Outcome (Global Assessment by the participating physicians)	During the Study Conduct

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate at which additional antibacterials were prescribed to treat the primary infection	During the study conduct
Rate of hospitalisation due to a complication of the primary infection	During the study conduct
Assessment of chest X-ray and sinus X-ray if available.	During the study conduct
Adverse Event (AE) and Serious Adverse Event (SAE) reported	from the inform consent signed up to the end of the study

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Won-Sik Lee, MD, Sanofi

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): October 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: December 1, 2005
• First Submitted That Met QC Criteria: December 1, 2005
• First Posted (Estimate): December 2, 2005

Study Record Updates

• Last Update Posted (Estimate): September 25, 2009
• Last Update Submitted That Met QC Criteria: September 24, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Infections; Respiratory Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Telithromycin
• Other Study ID Numbers: HMR3647A_4026