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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00707239




Registration number
NCT00707239
Ethics application status
Date submitted
26/06/2008
Date registered
30/06/2008
Date last updated
10/07/2012

Titles & IDs
Public title
Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia
Scientific 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
Secondary ID [1] 0 0
B1811004
Secondary ID [2] 0 0
3074K6-2000
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pneumonia, Bacterial 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tigecycline
Treatment: Drugs - tigecycline
Treatment: Drugs - imipenem/cilastatin

Experimental: A -

Experimental: B -

Active Comparator: C -


Treatment: Drugs: 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]).

Treatment: Drugs: 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]).

Treatment: Drugs: 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]).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to Day 24 to 35 (10 to 21 days after LDOT)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to Day 24 to 35 (10 to 21 days after LDOT)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to Day 24 to 35 (10 to 21 days after LDOT)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up to Day 24 to 35 (10 to 21 days after LDOT)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Nambour
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Victoria
Recruitment postcode(s) [1] 0 0
4560 - Nambour
Recruitment postcode(s) [2] 0 0
3128 - Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kentucky
Country [2] 0 0
United States of America
State/province [2] 0 0
Nebraska
Country [3] 0 0
United States of America
State/province [3] 0 0
West Virginia
Country [4] 0 0
Argentina
State/province [4] 0 0
Buenos Aires
Country [5] 0 0
Argentina
State/province [5] 0 0
Mendoza
Country [6] 0 0
Argentina
State/province [6] 0 0
Provincia de Buenos Aires
Country [7] 0 0
Brazil
State/province [7] 0 0
MG
Country [8] 0 0
Brazil
State/province [8] 0 0
RS
Country [9] 0 0
Brazil
State/province [9] 0 0
SP
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Chile
State/province [11] 0 0
Santiago
Country [12] 0 0
Colombia
State/province [12] 0 0
Antioquia
Country [13] 0 0
Colombia
State/province [13] 0 0
Bogota
Country [14] 0 0
Croatia
State/province [14] 0 0
Zagreb
Country [15] 0 0
France
State/province [15] 0 0
Argenteuil
Country [16] 0 0
Hungary
State/province [16] 0 0
Debrecen
Country [17] 0 0
Hungary
State/province [17] 0 0
Nyiregyhaza
Country [18] 0 0
Hungary
State/province [18] 0 0
Szekesfehervar
Country [19] 0 0
Hungary
State/province [19] 0 0
Vac
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Korea
Country [21] 0 0
Latvia
State/province [21] 0 0
Daugavpils
Country [22] 0 0
Latvia
State/province [22] 0 0
Riga
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Moscow
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Novosibirsk
Country [25] 0 0
Russian Federation
State/province [25] 0 0
St Petersburg
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Vsevolozhsk
Country [27] 0 0
Taiwan
State/province [27] 0 0
Tainan
Country [28] 0 0
Taiwan
State/province [28] 0 0
Taipei TOC
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00707239
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00707239