Linezolid in the Treatment of Hemodialysis Patients With Catheter-Related Gram-Positive Bloodstream Infections

Condition(s) targeted: Bacteremia; Gram-Positive Bacterial Infections

Intervention: Cefazolin IV (Drug); Linezolid IV (Drug); Vancomycin (IV) (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Pfizer

Official(s) and/or principal investigator(s):
Pfizer CT.gov Call Center, Study Director, Affiliation: Pfizer

This study will treat hemodialysis patients who have a central catheter that is thought to be infected with a specific bacteria (Gram positive bacteria).

Official title: Linezolid vs Vancomycin/Cefazolin in the Treatment of Hemodialysis Patients With Catheter-Related Gram-Positive Bloodstream Infections

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Microbiological efficacy of linezolid compared to vancomycin/cefazolin

Secondary outcome:

1.Clinical efficacy of linezolid compared to vancomycin/cefazolin

2.Incidence of complications during the study, such as metastatic infection, measured at the long-term follow-up visit (LTFU).

3.Pathogen eradication at Test of Cure (TOC) visit

Detailed description: Pfizer suspended enrollment on 21 August 2006 as a precautionary measure in light of the mortality imbalance seen in a similar study, and terminated the study on April 6, 2007 due to factors affecting the timeline to completion, such as slow enrollment and inclusion of sufficient evaluable subjects.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- To be eligible for this study, a patient must provide informed consent and must meet

all of the following criteria. No study procedures, including any baseline tests, should be performed until the patient (or parent/legally acceptable representative, if appropriate) legally signs the informed consent form.

- Male or female, 18 years of age or older and >= 40 kg body weight

- End-stage renal disease patients on hemodialysis with: A) Signs and symptoms of a

localized catheter-related infection (eg tenderness and/or pain, erythema, swelling, purulent exudates within 2 cm of entry site); OR B) A body temperature of >= 38. 0 C or < 36. 0 C (oral equivalent); OR C) A Gram-positive blood culture. If the Gram-positive isolate is S. aureus, it must be cultured from at least 1 culture bottle from either the peripheral set or the catheter set of culture bottles. For all other Gram-positive pathogens (eg, coagulase-negative staphylococci), isolates need to be cultured from at least 2 culture bottles of which one must be from the peripheral set. There must be no other obvious source of the bacteremia

- Presence of at least one of the following systemic signs of infection (may be obtained

up to 24 hours prior to baseline): *Hypotension, defined as systolic blood pressure <90 mmHg or its reduction by >= 40 mmHg from the patient's baseline, in the absence of other causes for hypotension; *Tachycardia defined as a pulse rate > 90 beats per minute; *Tachypnea defined as a respiratory rate > 20 breaths per minute or PACO2 <32 torr; *White blood count >10,000 cells/mm3 or < 4,000 cells/mm3, or with a differential count showing >10% band neutrophil forms.

- Patients on hemodialysis with tunneled or nontunneled catheters including antibiotic

coated hemodialysis catheters. Patients may have more than one concurrent catheter.

- Patients who are willing and able to comply with scheduled visits, treatment plan,

laboratory tests and other study procedures

Exclusion Criteria:

- Patients presenting with any of the following will not be included in this study:

- Catheter-related bloodstream infections caused by Gram-negative bacteria, fungi, mixed

cultures of Gram negative bacteria and Gram positive bacteria or mixed cultures of Gram positive/negative bacteria and fungi

- Patients with evidence of other infections resulting in bacteremia, such as clinical

or radiographic signs of osteomyelitis, endocarditis, skin/skin structure infection, pneumonia, urinary tract infection, joint infection, intraabdominal infection, septic thrombophlebitis or other infection

- Patients in whom the infected catheter cannot be removed

- Patients with permanent intravascular devices such as artificial vascular grafts,

implantable pacemakers or defibrillators; intra-aortic balloon pumps, and left ventricular assist device; intravascular transplants such as prosthetic cardiac valves; or non-intravascular devices such as peritoneal dialysis catheters; or neurosurgical devices such as ventriculo-peritoneal shunts, intra-cranial pressure monitors, or epidural catheters, prosthetic cardiac valves, prosthetic vascular grafts, or other internal prosthesis

- Females of child-bearing potential who are unable or unwilling to take adequate

contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant

- Identification of a pathogen resistant to linezolid or vancomycin

- Patients who are unlikely to survive through the treatment period and evaluation

- Administration of a glycopeptide antibiotic within 5 days prior to enrollment.

Administration of other potentially effective systemic Gram-positive antibiotics for more than 48 hours within 72 hours prior to enrollment unless the pathogen showed drug resistance

- Previous enrollment in this protocol

- Hypersensitivity to linezolid, vancomycin, gentamicin or one of their excipients (or

aztreonam if non-bacteremic Gram-negative coverage is required)

- Concurrent use of another investigational medication or use within 30 days of study

entry

- Patients with pressor and fluid-resistant hemodynamic compromise or pulmonary

embolism

Pfizer Investigational Site, Tel-Aviv 64239, Israel

Pfizer Investigational Site, Imperia 18100, Italy

Pfizer Investigational Site, Czestochowa 42-200, Poland

Pfizer Investigational Site, Nitra 950 01, Slovakia

Pfizer Investigational Site, Banska Bystrica 975 17, Slovakia

Pfizer Investigational Site, Hyderbad, Andhra Pradesh 500 082, India

Pfizer Investigational Site, Barranquilla, Atlantico, Colombia

Pfizer Investigational Site, BOGOTA, Cundinamarca, Colombia

Pfizer Investigational Site, Bogota, D.C, Colombia

Pfizer Investigational Site, New Delhi, Delhi 110 044, India

Pfizer Investigational Site, Bangalore, Karnataka 560 054, India

Pfizer Investigational Site, Bangalore, Karnataka 560 034, India

Pfizer Investigational Site, Baltimore, Maryland 21201, United States

Pfizer Investigational Site, Baltimore, Maryland 21201-1524, United States

Pfizer Investigational Site, Baltimore, Maryland 21230, United States

Pfizer Investigational Site, Chandigarh, Punjab 160 012, India

Pfizer Investigational Site, Chennai, Tamil Nadu 600 004, India

To obtain contact information for a study center near you, click here.

Starting date: September 2005
Last updated: September 5, 2007