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

Pneumonia, Bacterial Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00707239
• Other study ID #: 3074K6-2000
• Secondary ID: B1811004
• Status: Terminated
• Phase: Phase 2
• First received: June 26, 2008
• Last updated: June 5, 2012
• Start date: December 2008
• Est. completion date: June 2011

Study information

• Verified date: June 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 108
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Bacterial

Intervention

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]).
• 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]).
• 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]).

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Godoy Cruz	Mendoza
Argentina	Pfizer Investigational Site	La Plata	Provincia de Buenos Aires
Argentina	Pfizer Investigational Site	La Plata	Buenos Aires
Argentina	Pfizer Investigational Site	Provincia de Buenos Aires
Australia	Pfizer Investigational Site	Nambour	Queensland
Australia	Pfizer Investigational Site	Victoria
Brazil	Pfizer Investigational Site	Belo Horizonte	MG
Brazil	Pfizer Investigational Site	Porto Alegre	RS
Brazil	Pfizer Investigational Site	Sao Jose do Rio Preto	SP
Canada	Pfizer Investigational Site	Chicoutimi	Quebec
Canada	Pfizer Investigational Site	Trois-Rivieres	Quebec
Chile	Pfizer Investigational Site	Santiago
Colombia	Pfizer Investigational Site	Bogota
Colombia	Pfizer Investigational Site	Medellin	Antioquia
Croatia	Pfizer Investigational Site	Zagreb
France	Pfizer Investigational Site	Argenteuil
Hungary	Pfizer Investigational Site	Debrecen
Hungary	Pfizer Investigational Site	Nyiregyhaza
Hungary	Pfizer Investigational Site	Szekesfehervar
Hungary	Pfizer Investigational Site	Vac
Korea, Republic of	Pfizer Investigational Site	Seoul	Korea
Korea, Republic of	Pfizer Investigational Site	Seoul	Korea
Korea, Republic of	Pfizer Investigational Site	Seoul	Korea
Korea, Republic of	Pfizer Investigational Site	Seoul	Korea
Latvia	Pfizer Investigational Site	Daugavpils
Latvia	Pfizer Investigational Site	Riga
Latvia	Pfizer Investigational Site	Riga
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Novosibirsk
Russian Federation	Pfizer Investigational Site	St Petersburg
Russian Federation	Pfizer Investigational Site	St Petersburg
Russian Federation	Pfizer Investigational Site	Vsevolozhsk
Taiwan	Pfizer Investigational Site	Tainan
Taiwan	Pfizer Investigational Site	Tainan
Taiwan	Pfizer Investigational Site	Taipei
Taiwan	Pfizer Investigational Site	Taipei TOC
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Morgantown	West Virginia
United States	Pfizer Investigational Site	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Colombia,  Croatia,  France,  Hungary,  Korea, Republic of,  Latvia,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit	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.	Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])	No
Secondary	Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit	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.	Up to Day 24 to 35 (10 to 21 days after LDOT)	No
Secondary	Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit	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.	Up to Day 24 to 35 (10 to 21 days after LDOT)	No
Secondary	Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit	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.	Up to Day 24 to 35 (10 to 21 days after LDOT)	No
Secondary	Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit	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.	Up to Day 24 to 35 (10 to 21 days after LDOT)	No

External Links

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