Clinical trial NCT00108433: Linezolid in the Treatment of Hemodialysis Patients With Catheter-Related Gram-Positive Bloodstream Infections
Official title: Linezolid vs Vancomycin/Cefazolin in the Treatment of Hemodialysis Patients With Catheter-Related Gram-Positive Bloodstream Infections
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bacteremia
Gram-Positive Bacterial Infections
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-04-18
Enrollment: 61
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 treat hemodialysis patients who have a central catheter that is thought to be infected with a specific bacteria (Gram positive bacteria).

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Microbiological Response at Test-of-Cure (TOC) Visit
timeFrame: Short term follow-up (STFU) visit for TOC (2 to 3 weeks after the last dose of study medication)
Secondary outcomes:
measure: Number of Participants With Clinical Outcome Based on Sponsor's (Sp) and Investigator's (Ir) Assessment
timeFrame: EOT (within 72 hours after last dose of study medication), STFU visit for TOC (2 to 3 weeks after the last dose of study medication), Long term follow-up (LTFU) visit (6 to 8 weeks after the last dose of study medication)
measure: Number of Participants With Complications During Therapy
timeFrame: LTFU visit (6 to 8 weeks after the last dose of study medication)
measure: Percentage of Pathogens Eradicated
timeFrame: STFU visit for TOC (2 to 3 weeks after the last dose of study medication), LTFU visit (6 to 8 weeks after the last dose of study medication)
measure: Percentage of Participants With Eradication of Staphylococcus Aureus Nasal Colonization
timeFrame: STFU visit for TOC (2 to 3 weeks after the last dose of study medication), LTFU visit (6 to 8 weeks after the last dose of study medication)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Barranquilla
country: Colombia
facility: Pfizer Investigational Site
state: Atlantico
city: Bogota
country: Colombia
facility: Pfizer Investigational Site
state: Cundinamarca
city: Bogota
country: Colombia
facility: Pfizer Investigational Site
state: D.C
city: Hyderbad
country: India
facility: Pfizer Investigational Site
state: Andhra Pradesh
city: New Delhi
country: India
facility: Pfizer Investigational Site
state: Delhi
city: Bangalore
country: India
facility: Pfizer Investigational Site
state: Karnataka
city: Bangalore
country: India
facility: Pfizer Investigational Site
state: Karnataka
city: Chandigarh
country: India
facility: Pfizer Investigational Site
state: Punjab
city: Chennai
country: India
facility: Pfizer Investigational Site
state: Tamil Nadu
city: Tel-Aviv
country: Israel
facility: Pfizer Investigational Site
city: Imperia
country: Italy
facility: Pfizer Investigational Site
city: Czestochowa
country: Poland
facility: Pfizer Investigational Site
city: Banska Bystrica
country: Slovakia
facility: Pfizer Investigational Site
city: Nitra
country: Slovakia
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Almeida BM, Moreno DH, Vasconcelos V, Cacione DG. Interventions for treating catheter-related bloodstream infections in people receiving maintenance haemodialysis. Cochrane Database Syst Rev. 2022 Apr 1;4(4):CD013554. doi: 10.1002/14651858.CD013554.pub2.