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

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.