Study to Evaluate Eye Function in Patients Taking Linezolid for Six Weeks or Greater

Prospective Study Of Ophthalmologic Function In Patients Receiving Linezolid For Six Weeks Or Greater

To understand and characterize the effects of linezolid on the optic nerve by observing and following patients who have been treated with linezolid for six weeks or longer for the development of signs or symptoms of visual disturbance or eye disorders.

Study Overview

• Status: Terminated
• Conditions: Optic Nerve Diseases
• Intervention / Treatment: Drug: Zyvox - linezolid; Drug: Matched control

Detailed Description

Characterize Optic Side Effect

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Genova, Italy, 16132
    • Università di Genova
  • Genova, Italy, 16132
    • Azienda Ospedaliera Universitaria di San Martino
  • Genova, Italy, 16132
    • Ospedale San Martino, Clinica Malattie Infettive
  • Udine, Italy, 33100
    • Clinica Malattie Infettive, Azienda Ospedaliero Universitaria Santa Maria della Misericordia
• Sweden
  • Stockholm, Sweden, 141 86
    • Infektionskliniken 1-73, Karolinska Universitetssjukhuset Huddinge
• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernards Research Center
  • Florida
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute, PA
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Department of Medicine/Division of Infectious Diseases
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine, Partnership Comprehensive Care Practice
    • Pittsburgh, Pennsylvania, United States, 15206
      • Associates in Infectious Disease and Tropical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects who are 18 years of age or older.
• Subjects in Treated Group:
• Subjects must have received linezolid 600 mg BID for six weeks or greater and be currently on drug (or have received linezolid within 7 days of baseline evaluation).
• Subjects who have current signs or symptoms compatible with linezolid toxicity (i.e. optic or peripheral neuropathy) may be enrolled in the study if they are on linezolid at time of baseline evaluation (or have received linezolid within 7 days of baseline evaluation).
• Linezolid may be discontinued at any time at the primary physician's discretion and remain on the study.
• Women of childbearing potential must use adequate contraception
• Subjects in Control Group:
• Subjects will have a diagnosis similar to patients in the treated group and similar important co-morbidities and epidemiologic factors if possible.

Exclusion Criteria:

• Subject in Treated Group:
• Subjects with a known presence of optic or peripheral nerve damage due to another illness, condition or medication.
• Subjects with a pre-existing or a diagnosis at time of screening visit of an ophthalmologic condition that would adversely affect the study testing protocol (e.g. dense cataracts, macular degeneration, retinitis pigmentosa).
• Subjects who are currently receiving or anticipated to receive another medication, antibiotic or other, that has known potential to produce ocular or neurologic toxicity indistinguishable from that caused by linezolid or lactic acidosis.
• Subjects with a history of significant exposure, in the opinion of the investigator and with prior discussion with the medical monitor, to medications known to produce optic or peripheral neuropathy.
• Subjects with an active communicable disease (i.e., tuberculosis assessed as currently communicable) and subjects on active treatment for tuberculosis or other mycobacterial disease that include drugs that have known potential to produce ocular or neurologic toxicity.
• Subjects with severe liver disease or abnormal liver function test.
• Subjects in Control Group:
• Subjects must not currently be taking linezolid or have received it for more than 7 days at any time.
• Subjects with a known presence of optic or peripheral nerve damage due to another illness, condition or medication.
• Subjects with a pre-existing or a diagnosis at the screening visit of an ophthalmologic condition that would adversely affect the study testing protocol (e.g. dense cataracts, macular degeneration, retinitis pigmentosa).
• Subjects who are currently receiving another medication, antibiotic or other, that has known potential to produce ocular or neurologic toxicity indistinguishable from that caused by linezolid or lactic acidosis.
• Subjects with a history of significant exposure, in the opinion of the investigator and with prior discussion with the medical monitor, to medications known to produce optic or peripheral neuropathy.
• Subjects with an active communicable disease (i.e., tuberculosis assessed as currently communicable) and subjects on active treatment for tuberculosis or other mycobacterial disease that include drugs that have known potential to produce ocular or neurologic toxicity.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linezolid; Subjects have received at least 6 weeks of linezolid therapy (600 mg BID). Continued duration of linezolid treatment is based on treating physician's benefit/risk assessment. A matching control who did not receive linezolid will be selected for each linezolid treated subject.	Drug: Zyvox - linezolid; Observation and testing in patients for whom their treating physician has determined linezolid is an appropriate therapy. Eye tests performed for subjects who have received linezolid for at least 6 weeks and matching controls who have received other antibiotics for similar types of infections.
Active Comparator: Matched control; Control subjects individually matched to linezolid subjects (on age, gender and type of infection) who received at least 6 weeks of antibiotics other than linezolid. Control group assessed only at baseline visit to assess presence of background abnormalities in the study test panel.	Drug: Matched control; Matched controls received an antibiotic other than linezolid for at least 6 weeks prior to baseline visit. The control group had only a baseline visit and there were no post baseline study visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With an Adverse Event	Through and including 28 calendar days after the last administration of the investigational product

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants by Clinical Outcome of Infection at End of Study	Clinical response was evaluated at the End of Study visit (30 days after last dose) as Cure, Improvement, Failure, Unknown or Other. Clinical response was based primarily on the global assessment of the clinical presentation of the subject made by the investigator at that evaluation timepoint. The clinical response classifications were defined as follows. Cure: Resolution of the clinical signs and symptoms of infection, when compared to Baseline. No additional antimicrobial treatment is required for the disease under study. Improvement: Improvement in 2 or more, but not all, of the clinical signs and symptoms of infection, when compared with Baseline. No additional antimicrobial treatment is required for the disease under study. Failure: Persistence or progression of Baseline clinical signs and symptoms of infection, or development of new clinical findings consistent with active infection. Unknown: Inability to assess clinical response.	At End of Study visit

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 28, 2006
• First Submitted That Met QC Criteria: July 28, 2006
• First Posted (Estimate): August 2, 2006

Study Record Updates

• Last Update Posted (Estimate): June 26, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Optic neuropathy following long-term linezolid use
• Additional Relevant MeSH Terms: Eye Diseases; Cranial Nerve Diseases; Nervous System Diseases; Optic Nerve Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid
• Other Study ID Numbers: A5951110; 2006-002303-14 (EudraCT Number)