Clinical trial NCT00707239: Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pneumonia, Bacterial
Keywords: Hospital-acquired pneumonia
Ventilator-associated pneumonia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-06-30
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit
timeFrame: Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])
Secondary outcomes:
measure: Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit
timeFrame: Up to Day 24 to 35 (10 to 21 days after LDOT)
measure: Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit
timeFrame: Up to Day 24 to 35 (10 to 21 days after LDOT)
measure: Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit
timeFrame: Up to Day 24 to 35 (10 to 21 days after LDOT)
measure: Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit
timeFrame: Up to Day 24 to 35 (10 to 21 days after LDOT)
Other outcomes:
measure: Number of Participants Who Experienced Nausea or Vomiting
timeFrame: Baseline up to Day 29 to Day 35 (15 to 21 days after LDOT)
measure: Number of Participants With Abnormal Laboratory Examinations
timeFrame: Baseline up to Day 24 to Day 35 (10 to 21 days after LDOT)
measure: Number of Participants With Abnormal Electrocardiogram (ECG)
timeFrame: Baseline up to Day 14 or LDOT
measure: Maximum Observed Serum Concentration (Cmax) of Tigecycline
timeFrame: Day 3, 4 or 5
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Tigecycline
timeFrame: Day 3, 4 or 5
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Tigecycline
timeFrame: Day 3, 4 or 5
measure: Clearance (CL) of Tigecycline
timeFrame: Day 3, 4 or 5
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Tigecycline
timeFrame: Day 3, 4 or 5
measure: Correlation of AUC (0-24) of Tigecycline With Nausea and Vomiting
timeFrame: Baseline up to Day 29 to 35 (15 to 21 days after LDOT)
measure: Correlation of AUC(0-24) to Minimum Inhibitory Concentration (MIC) Ratio (AUC [0-24]/MIC) of Tigecycline With Clinical Outcome
timeFrame: Up to Day 24 to 35 (10 to 21 days after LDOT)
measure: Correlation of AUC(0-24) to Minimum Inhibitory Concentration (MIC) Ratio (AUC [0-24]/MIC) of Tigecycline With Microbiological Outcome
timeFrame: Up to Day 24 to 35 (10 to 21 days after LDOT)
measure: Maximum Observed Plasma Concentration of Procalcitonin (Cmaxpd) and Predicted Procalcitonin Plasma Concentration at 24 Hours (Cpd,24) and 48 Hours (Cpd,48)
timeFrame: Baseline up to Day 6
measure: Time to Reach Half of the Maximum Observed Plasma Concentration and Time to Normalization of Concentrations (Tnorm) of Procalcitonin
timeFrame: Baseline up to Day 6
measure: Duration of Intravenous Antibiotic Treatment, Hospital and Intensive Care Unit (ICU) Stay
timeFrame: Baseline up to Day 44 (30 days after LDOT)
Locations:
city: Louisville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Omaha
country: United States
facility: Pfizer Investigational Site
state: Nebraska
city: Morgantown
country: United States
facility: Pfizer Investigational Site
state: West Virginia
city: La Plata
country: Argentina
facility: Pfizer Investigational Site
state: Buenos Aires
city: Godoy Cruz
country: Argentina
facility: Pfizer Investigational Site
state: Mendoza
city: La Plata
country: Argentina
facility: Pfizer Investigational Site
state: Provincia de Buenos Aires
city: Provincia de Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Nambour
country: Australia
facility: Pfizer Investigational Site
state: Queensland
city: Victoria
country: Australia
facility: Pfizer Investigational Site
city: Belo Horizonte
country: Brazil
facility: Pfizer Investigational Site
state: MG
city: Porto Alegre
country: Brazil
facility: Pfizer Investigational Site
state: RS
city: Sao Jose do Rio Preto
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Chicoutimi
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Santiago
country: Chile
facility: Pfizer Investigational Site
city: Medellin
country: Colombia
facility: Pfizer Investigational Site
state: Antioquia
city: Bogota
country: Colombia
facility: Pfizer Investigational Site
city: Zagreb
country: Croatia
facility: Pfizer Investigational Site
city: Argenteuil
country: France
facility: Pfizer Investigational Site
city: Debrecen
country: Hungary
facility: Pfizer Investigational Site
city: Nyiregyhaza
country: Hungary
facility: Pfizer Investigational Site
city: Szekesfehervar
country: Hungary
facility: Pfizer Investigational Site
city: Vac
country: Hungary
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
state: Korea
city: Daugavpils
country: Latvia
facility: Pfizer Investigational Site
city: Riga
country: Latvia
facility: Pfizer Investigational Site
city: Riga
country: Latvia
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Pfizer Investigational Site
city: St Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
city: St Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
city: Vsevolozhsk
country: Russian Federation
facility: Pfizer Investigational Site
city: Tainan
country: Taiwan
facility: Pfizer Investigational Site
city: Tainan
country: Taiwan
facility: Pfizer Investigational Site
city: Taipei TOC
country: Taiwan
facility: Pfizer Investigational Site
city: Taipei
country: Taiwan
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013 Apr;57(4):1756-62. doi: 10.1128/AAC.01232-12. Epub 2013 Jan 28.