Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00707239
First received: June 26, 2008
Last updated: June 5, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Pneumonia, Bacterial
Drug: tigecycline
Drug: imipenem/cilastatin
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: A Phase 2, Multicenter, Randomized, Double-Blind, Comparative Study Of The Safety And Efficacy of 2 Doses Of Tigecycline Versus Imipenem/Cilastatin For The Treatment Of Subjects With Hospital-Acquired Pneumonia

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit [ Time Frame: Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT]) ] [ Designated as safety issue: No ]
    Clinical response: Cure=All initial signs/symptoms of pneumonia (SSx) improved; chest x-ray (CXR) improved/stable; no other antibiotics for pneumonia; no worsening or new SSx. Failure=Persistence or worsening SSx; no clinical improvement or initial improvement with clinically important worsening; other antimicrobials for pneumonia; CXR progression; death > study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reasons (e.g., lost to follow-up); death in 2 days after 1st dose for any reason, or >2 days but before TOC visit for non-pneumonia reason.


Secondary Outcome Measures:
  • Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit [ Time Frame: Up to Day 24 to 35 (10 to 21 days after LDOT) ] [ Designated as safety issue: No ]
    Clinical response: Cure=All initial SSx improved; CXR improved/stable; no other antibiotics for pneumonia; no worsening or new SSx. Failure=Persistence or worsening SSx; no clinical improvement or initial improvement with clinically important worsening; other antimicrobials for pneumonia; CXR progression; death > study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reasons (e.g., lost to follow-up); death in 2 days after 1st dose for any reason, or >2 days but before TOC visit for non-pneumonia reason.

  • Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit [ Time Frame: Up to Day 24 to 35 (10 to 21 days after LDOT) ] [ Designated as safety issue: No ]
    Clinical response: Cure=All initial SSx improved; CXR improved/stable; no other antibiotics for pneumonia; no worsening or new SSx. Failure=Persistence or worsening SSx; no clinical improvement or initial improvement with clinically important worsening; other antimicrobials for pneumonia; CXR progression; death > study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reasons (e.g., lost to follow-up); death in 2 days after 1st dose for any reason, or >2 days but before TOC visit for non-pneumonia reason.

  • Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit [ Time Frame: Up to Day 24 to 35 (10 to 21 days after LDOT) ] [ Designated as safety issue: No ]
    Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for participants with a clinical response of failure; Indeterminate=unable to determine outcome for non-study drug/infection reasons; no baseline isolate; death in 2 days after 1st dose for any reason, or >2 days but before TOC visit for non-pneumonia reason.

  • Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit [ Time Frame: Up to Day 24 to 35 (10 to 21 days after LDOT) ] [ Designated as safety issue: No ]
    Microbiological response assessed at participant level. Eradication = baseline isolate not present in repeat culture from the original infection site; Presumed Eradication = clinical response of cure precluded the availability of a specimen for culture; Persistence = baseline isolate present in repeat culture from the original infection site; Presumed Persistence = culture data not available for participants with a clinical response of failure; Superinfection = culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure.


Enrollment: 108
Study Start Date: December 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: tigecycline
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]).
Experimental: B Drug: tigecycline
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]).
Active Comparator: C Drug: imipenem/cilastatin
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]).

Detailed Description:

The sponsor internal decision has been taken to close the study on 15 of July 2011, due to difficulties in enrollment. This decision was not based on any safety issues.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00707239

  Show 40 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00707239     History of Changes
Other Study ID Numbers: 3074K6-2000, B1811004
Study First Received: June 26, 2008
Results First Received: June 5, 2012
Last Updated: June 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Hospital-acquired pneumonia
Ventilator-associated pneumonia

Additional relevant MeSH terms:
Pneumonia, Bacterial
Pneumonia
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cilastatin
Imipenem
Tigecycline
Minocycline
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014