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

This study has been terminated.
(Study was stopped due to poor enrollment on 28 Feb 2012. Reason for termination was not due to safety concerns.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00359632
First received: July 28, 2006
Last updated: June 3, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Optic Nerve Diseases
Drug: Zyvox - linezolid
Drug: Matched control
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Prospective Study Of Ophthalmologic Function In Patients Receiving Linezolid For Six Weeks Or Greater

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With an Adverse Event [ Time Frame: Through and including 28 calendar days after the last administration of the investigational product ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of Participants by Clinical Outcome of Infection at End of Study [ Time Frame: At End of Study visit ] [ Designated as safety issue: No ]
    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.


Enrollment: 34
Study Start Date: November 2008
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

Characterize Optic Side Effect

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00359632

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

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00359632     History of Changes
Other Study ID Numbers: A5951110, 2006-002303-14
Study First Received: July 28, 2006
Results First Received: December 16, 2014
Last Updated: June 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Optic neuropathy following long-term linezolid use

Additional relevant MeSH terms:
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Linezolid
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015