Optic Nerve Diseases
Conditions
Keywords
Optic neuropathy following long-term linezolid use
Brief summary
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.
Detailed description
Characterize Optic Side Effect
Interventions
DRUGZyvox - 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.
DRUGMatched 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.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants by Clinical Outcome of Infection at End of Study | At End of Study visit | 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. |
Countries
Italy, Sweden, United States
Participant flow
Recruitment details
Nine centers (2 centers in Italy, 1 center in Sweden, and 6 centers in the US) enrolled subjects for inclusion in the study. Sites were selected based on their capability to perform the comprehensive testing and to treat types of infections that might require therapy with linezolid for 6 weeks or longer.
Pre-assignment details
There were separate selection criteria for subjects in the treated and control groups. At the Screening/Baseline visit (Day 1), subjects were eligible for the study after verification that they met the relevant inclusion/exclusion criteria and the study had been explained to them.
Participants by arm
| Arm | Count |
|---|---|
| Linezolid Participants received linezolid either as tablets, PO or as an IV infusion at a dose of 600 mg, BID. Mode of administration and duration of treatment was at the discretion of the investigator, but for study purposes, the participant had to receive linezolid treatment for a minimum of 6 weeks (at least 42 days). | 24 |
| Control Control participants individually matched to linezolid participants (on age, gender, and type of infection) received antibiotics other than linezolid per standard of care at the discretion of the treating investigator, for at least 6 weeks (at least 42 days). The control group was only assessed at the baseline visit to identify the presence of background abnormalities in the study test panel. | 9 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Non-compliance with visit schedule | 1 | 0 |
Baseline characteristics
| Characteristic | Linezolid | Control | Total |
|---|---|---|---|
| Age, Continuous | 53.4 Years STANDARD_DEVIATION 13.38 | 50.1 Years STANDARD_DEVIATION 11.86 | 52.5 Years STANDARD_DEVIATION 12.89 |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 24 | 1 / 9 |
| serious Total, serious adverse events | 6 / 24 | 0 / 9 |
Outcome results
Primary
Percentage of Participants With an Adverse Event
Time frame: Through and including 28 calendar days after the last administration of the investigational product
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Linezolid | Percentage of Participants With an Adverse Event | Serious adverse events, % | 25.0 Percentage of Participants |
| Linezolid | Percentage of Participants With an Adverse Event | Discontinued due to adverse events, % | 29.2 Percentage of Participants |
| Linezolid | Percentage of Participants With an Adverse Event | Severe adverse events, % | 12.5 Percentage of Participants |
| Linezolid | Percentage of Participants With an Adverse Event | Dose Reduced or Temporary Discontinuation, % | 12.5 Percentage of Participants |
| Linezolid | Percentage of Participants With an Adverse Event | Adverse events, % | 83.3 Percentage of Participants |
| Control | Percentage of Participants With an Adverse Event | Dose Reduced or Temporary Discontinuation, % | 0 Percentage of Participants |
| Control | Percentage of Participants With an Adverse Event | Adverse events, % | 11.1 Percentage of Participants |
| Control | Percentage of Participants With an Adverse Event | Serious adverse events, % | 0 Percentage of Participants |
| Control | Percentage of Participants With an Adverse Event | Severe adverse events, % | 0 Percentage of Participants |
| Control | Percentage of Participants With an Adverse Event | Discontinued due to adverse events, % | 0 Percentage of Participants |
Secondary
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.
Time frame: At End of Study visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Linezolid | Percentage of Participants by Clinical Outcome of Infection at End of Study | Other, % | 9.5 Percentage of Participants |
| Linezolid | Percentage of Participants by Clinical Outcome of Infection at End of Study | Cure, % | 47.6 Percentage of Participants |
| Linezolid | Percentage of Participants by Clinical Outcome of Infection at End of Study | Improvement, % | 42.9 Percentage of Participants |
| Linezolid | Percentage of Participants by Clinical Outcome of Infection at End of Study | Failure, % | 0 Percentage of Participants |
| Linezolid | Percentage of Participants by Clinical Outcome of Infection at End of Study | Unknown, % | 0 Percentage of Participants |