Optic Neuropathy, Ischemic
Conditions
Keywords
Optic Neuropathy Acute NAION PDE5 Inhibitor
Brief summary
The objective of this non-interventional study is to examine whether use of Phosphodiesterase Inhibitors (PDE5s), including use of sildenafil, vardenafil, or tadalafil, triggers the onset of acute NAION.
Detailed description
Sites will identify patients who meet the entry criteria during the conduct of their normal practice. Patients meeting these criteria will be offered participation in the study after reading and completing an informed consent document.
Interventions
DRUGNo intervention
No intervention occurs in this observational study.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Observational model
CASE_CROSSOVER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male aged ≥45 years; * Experienced abrupt visual change in only 1 eye
Exclusion criteria
* Pain determined by an ophthalmologist to be consistent with an inflammatory/arteritic process or optic neuritis; * History of NAION or optic neuritis. * Participation in other studies within 60 days prior to entry in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite NAION Cases | 30-day period prior to onset of NAION symptoms | Adjudication committee classified participants as Definite, Possible, or Non-NAION cases, or insufficient information available or unable to adjudicate. Case window: 1 day preceding symptom onset day; 29 control windows: 29 days preceding case window. A case or control window was considered exposed if: sildenafil/vardenafil was used on that day and/or previous day; tadalafil was used on that day and/or any of previous 4 days. In this analysis, each participant contributed exposure information for 1 case window and 29 control windows. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite or Possible NAION Cases | 30-day period prior to onset of NAION symptoms | Adjudication committee classified participants as Definite, Possible, or Non-NAION cases, or insufficient information available or unable to adjudicate. Case window: 1 day preceding symptom onset day; 29 control windows: 29 days preceding case window. A case or control window was considered exposed if: sildenafil/vardenafil was used on that day and/or previous day; tadalafil was used on that day and/or any of previous 4 days. In this analysis, each participant contributed exposure information for 1 case window and 29 control windows. |
| Number of Weeks Exposed to PDE5i During 1-Week Case Window and 7 1-Week Control Windows Among Participants Adjudicated as Definite NAION Cases | 60-day period prior to onset of NAION symptoms | Adjudication Committee classified participants as Definite, Possible, or Non-NAION cases, or insufficient information available or unable to adjudicate. Case window: 1 week preceding symptom onset day; 7 control windows: 7 weeks preceding case window. 1-week case or control window was considered exposed if any of 7 days were classified as exposed (sildenafil/vardenafil used on given day and/or previous day, or tadalafil used on given day and/or previous 4 days). In this analysis, each participant contributed exposure information for 1 case window and 7 control windows. |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Potential NAION Cases With PDE5i Exposure Participants who met pre-defined potential acute NAION criteria and were exposed to PDE5i (sildenafil, vardenafil or tadalafil) during the 60 days prior to NAION symptom onset were observed. | 76 |
| Potential NAION Cases Without PDE5i Exposure Participants who met pre-defined potential acute NAION criteria and were not exposed to PDE5i (sildenafil, vardenafil or tadalafil) during the 60 days prior to NAION symptom onset were observed. | 597 |
| Total | 673 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 0 | 2 |
Baseline characteristics
| Characteristic | Potential NAION Cases With PDE5i Exposure | Potential NAION Cases Without PDE5i Exposure | Total |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 7.3 | 62.3 years STANDARD_DEVIATION 10.2 | 62.3 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 76 Participants | 597 Participants | 673 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 673 |
| serious Total, serious adverse events | 2 / 673 |
Outcome results
Primary
Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite NAION Cases
Adjudication committee classified participants as Definite, Possible, or Non-NAION cases, or insufficient information available or unable to adjudicate. Case window: 1 day preceding symptom onset day; 29 control windows: 29 days preceding case window. A case or control window was considered exposed if: sildenafil/vardenafil was used on that day and/or previous day; tadalafil was used on that day and/or any of previous 4 days. In this analysis, each participant contributed exposure information for 1 case window and 29 control windows.
Time frame: 30-day period prior to onset of NAION symptoms
Population: Full Analysis Set (FAS) included all participants who signed informed consent, were eligible for study, reported exposure to PDE5i within 60 days prior to participant-reported onset of NAION symptoms. N (number of participants analyzed) represents Definite NAION cases with PDE5i exposure on at least 1 day but not all 30 days prior to symptom onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Potential NAION Cases With PDE5i Exposure/ Case Window | Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite NAION Cases | 14 exposed days |
| Potential NAION Cases With PDE5i Exposure/ Control Window | Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite NAION Cases | 248 exposed days |
Comparison: Conditional logistic regression was stratified by participant.p-value: 0.03395% CI: [1.06, 4.34]Conditional logistic regression
Other Pre-specified
Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite or Possible NAION Cases
Adjudication committee classified participants as Definite, Possible, or Non-NAION cases, or insufficient information available or unable to adjudicate. Case window: 1 day preceding symptom onset day; 29 control windows: 29 days preceding case window. A case or control window was considered exposed if: sildenafil/vardenafil was used on that day and/or previous day; tadalafil was used on that day and/or any of previous 4 days. In this analysis, each participant contributed exposure information for 1 case window and 29 control windows.
Time frame: 30-day period prior to onset of NAION symptoms
Population: FAS included all participants who signed informed consent, were eligible for study and reported exposure to PDEi within 60 days prior to participant reported-onset of NAION symptoms. N (number of participants analyzed) represents Definite or Possible NAION cases with PDE5i exposure on at least 1 day but not all 30 days prior to symptom onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Potential NAION Cases With PDE5i Exposure/ Case Window | Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite or Possible NAION Cases | 22 exposed days |
| Potential NAION Cases With PDE5i Exposure/ Control Window | Number of Days Exposed to PDE5i During 1-Day Case Window and 29 1-Day Control Windows Among Participants Adjudicated as Definite or Possible NAION Cases | 374 exposed days |
Comparison: Conditional logistic regression was stratified by participant.p-value: 0.00395% CI: [1.33, 4.19]Conditional logistic regression
Other Pre-specified
Number of Weeks Exposed to PDE5i During 1-Week Case Window and 7 1-Week Control Windows Among Participants Adjudicated as Definite NAION Cases
Adjudication Committee classified participants as Definite, Possible, or Non-NAION cases, or insufficient information available or unable to adjudicate. Case window: 1 week preceding symptom onset day; 7 control windows: 7 weeks preceding case window. 1-week case or control window was considered exposed if any of 7 days were classified as exposed (sildenafil/vardenafil used on given day and/or previous day, or tadalafil used on given day and/or previous 4 days). In this analysis, each participant contributed exposure information for 1 case window and 7 control windows.
Time frame: 60-day period prior to onset of NAION symptoms
Population: FAS population. N (number of participants analyzed) represents Definite NAION cases with PDE5i exposure on at least 1 day but not all 30 days or every week within 60 days prior to symptom onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Potential NAION Cases With PDE5i Exposure/ Case Window | Number of Weeks Exposed to PDE5i During 1-Week Case Window and 7 1-Week Control Windows Among Participants Adjudicated as Definite NAION Cases | 23 exposed weeks |
| Potential NAION Cases With PDE5i Exposure/ Control Window | Number of Weeks Exposed to PDE5i During 1-Week Case Window and 7 1-Week Control Windows Among Participants Adjudicated as Definite NAION Cases | 91 exposed weeks |
Comparison: Conditional logistic regression was stratified by participant.p-value: <0.00195% CI: [1.7, 7.69]Conditional logistic regression