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

Phase 2

Terminated

Conditions: Pneumonia, Bacterial

Interventions: Drug: tigecycline
Drug: imipenem/cilastatin

Registration Number: NCT00707239

Lead Sponsor: Pfizer

Brief 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 108

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	tigecycline	-
C	imipenem/cilastatin	-
A	tigecycline	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit	Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])	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

Name	Time	Method
Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit	Up to Day 24 to 35 (10 to 21 days after LDOT)	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	Up to Day 24 to 35 (10 to 21 days after LDOT)	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	Up to Day 24 to 35 (10 to 21 days after LDOT)	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	Up to Day 24 to 35 (10 to 21 days after LDOT)	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.