Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia
Condition: Pneumonia, Bacterial
MeSH terms: Pneumonia; Healthcare-Associated Pneumonia; Pneumonia, Bacterial
Intervention: tigecycline; tigecycline; imipenem/cilastatin
Intervention description: An initial intravenous (IV) loading dose of 150 mg of tigecycline, followed by 75 mg of IV tigecycline approximately every 12 hours (q12h), for up to 14 consecutive days. Ceftazidime 2 g IV approximately every 8 hours, an aminoglycoside (tobramycin 7mg/kg daily or amikacin 20 mg/kg daily) and vancomycin placebo given at the start of therapy (unless it is known at baseline that the subject does not have Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus [MRSA]).; An initial intravenous (IV) loading dose of 200 mg of tigecycline, followed by 100 mg of IV tigecycline approximately every 12 hours (q12h), for up to 14 consecutive days. Ceftazidime 2 g IV approximately every 8 hours, an aminoglycoside (tobramycin 7mg/kg daily or amikacin 20 mg/kg daily) and vancomycin placebo given at the start of therapy (unless it is known at baseline that the subject does not have Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus [MRSA]).; Imipenem/cilastatin 1g intravenous (IV) will be administered approximately every 8 hours, for up to 14 consecutive days. In addition vancomycin 15 mg/kg IV approximately every 12 hours (q12h), an aminoglycoside (tobramycin 7mg/kg daily or amikacin 20 mg/kg daily) and ceftazidime placebo will be given at the start of therapy (unless it is known at baseline that the subject does not have Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus [MRSA]).
Intervention MeSH terms: Imipenem; Tigecycline; Cilastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hospital-acquired pneumonia; Ventilator-associated pneumonia

Summary:

      This study will compare the safety and efficacy of a tigecycline regimen versus an
      imipenem/cilastatin regimen for the treatment of subjects who are hospitalized with
      hospital-acquired pneumonia (HAP). At least 70% of enrolled subjects will have
      ventilator-associated pneumonia (VAP). Two dose levels of tigecycline will be assessed and
      compared to imipenem/cilastatin in parallel. Subjects will receive intravenous therapy from a
      minimum of 7 & up to 14 consecutive days, the exact duration will be at the decision of the
      investigator based on the subject's condition. Additional protocol specified antibiotics may
      be given to ensure appropriate coverage. A final assessment at test-of-cure (TOC) visit will
      be done 10 to 21 days after the last day of therapy. The total duration of subject
      participation will be between 17 and 44 days, including a follow up period of 30 days after
      the last day of therapy for SAEs.

      Subjects will be followed for safety and efficacy. The safety assessment will include:
      physical examinations, vital signs, assessment of the clinical signs and symptoms of
      pneumonia, collection of adverse events, 12-lead ECG, collection of samples for hematology,
      serum chemistries, and coagulation parameters, & a serum or urine pregnancy test before study
      entry for women of childbearing potential. The clinical and microbiological efficacy will
      both be evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects, greater than or equal to 18 years of age, known or suspected
             to have acute hospital-acquired pneumonia (HAP).

          -  Acute HAP is defined as pneumonia with onset of symptoms:

               1. Greater than or equal to 48 hours after admission to an acute care hospital or
                  chronic care facility such as a skilled nursing home facility or rehabilitation
                  unit. Or

               2. Less than or equal to 7 days after the subject was discharged from the hospital.
                  The initial hospitalization must have been greater than or equal to 3 days
                  duration.

          -  VAP is defined as: onset of symptoms of pneumonia greater than or equal to 48 hours
             after endotracheal intubation.

          -  Presence of a new or evolving infiltrate on a chest x-ray film, presence of fever or
             leukocytosis, respiratory failure requiring mechanical ventilation or presence of 2 of
             the following clinical signs and symptoms: cough, dyspnea or tachypnea, pleuritic
             chest pain, rales and/or evidence of pulmonary consolidation, hypoxemia, or purulent
             sputum production.

        Exclusion Criteria:

          -  Subjects with other significant underlying conditions that would make it difficult to
             evaluate the subjects or make it unlikely to complete the therapy or that would
             increase their risk by participating in the study, infection with organisms known to
             be resistant, contraindication, or hypersensitivity to any of the test articles.