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

Pfizer

Status and phase

Terminated

Phase 3

Conditions

Bacteremia

Gram-Positive Bacterial Infections

Treatments

Drug: Linezolid IV

Drug: Vancomycin (IV)

Drug: Cefazolin IV

Study type

Interventional

Funder types

Industry

Identifiers

NCT00108433

A5951105

Details and patient eligibility

About

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

Full 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.

Enrollment

61 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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