Cataract
Conditions
Brief summary
The purpose of this study is to evaluate the penetration of levofloxacin and dexamethasone 21-phosphate into the aqueous humour after ocular administration in combination or as single active ingredients.
Detailed description
In most cases, postoperative care after cataract surgery consists of antiinflammatory and antibacterial drug therapy. The use of an ophthalmic solution containing the combination of a steroid and an antibiotic is routinely used in clinical practice; however, treatment duration could favour the emergence of antibiotic resistance. The study treatment associating a broad-spectrum antibiotic with a highly effective corticosteroid that can be used for a short period of time (one week) is therefore of considerable interest. The aim of this study is to measure the concentrations of levofloxacin and dexamethasone in the aqueous humour after topical application of the combined ophthalmic solution and its single components.
Interventions
DRUGLevofloxacin + Dexamethasone
Levofloxacin + Dexamethasone ophthalmic solution + dexamethasone 21-phosphate administered twice: 90(±15) min. and 60(±15) min. before limbal paracentesis.
DRUGLevofloxacin
Levofloxacin ophthalmic solution (Oftaquix®) administered twice: 90 (±15) min. and 60 (±15) min. before limbal paracentesis).
DRUGDexamethasone
Dexamethasone ophthalmic solution (Tamesad®) administered twice: 90 (±15) min. and 60 (±15) min. before Limbal paracentesis.
Sponsors
NTC srl
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
Single
Intervention model description
A randomized, assessor-blinded, parallel-group study.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent 2. Male or female patients, aged ≥40 years 3. Patient undergoing phacoemulsification 4. Corneal thickness between 450 μm and 600 μm as measured by means of pachymetry 5. Corneal integrity confirmed by means of fluorescein test 6. Adequate pupil dilation assessed at screening 7. Female patients of childbearing potential must have a negative pregnancy test 8. Ability to fully understand all study procedures
Exclusion criteria
1. Corneal epithelium integrity not confirmed by fluorescein test 2. History of corneal disease or dystrophy 3. History of ocular trauma with corneal damage 4. History of acute ocular inflammation (including uveitis) in the 6 months prior to screening 5. Previous ocular surgery (including laser treatment) 6. Glaucoma 7. Treatment with an ophthalmic investigational drug in the 3 months prior to screening 8. Treatment with any topical ocular drug within 12 hours before start of cataract surgery other than study drugs and instillation of topical anaesthetic within 10 minutes before start of surgery 9. Treatment with any topical steroid or antibiotic drug in the 7 days prior to cataract surgery 10. Treatment with any systemic steroid or antibiotic drug in the 7 days prior to cataract surgery 11. Known hypersensitivity to levofloxacin, other fluoroquinolones or dexamethasone 12. Pregnant or lactating women 13. Patients who have received any investigational drug during the preceding 30 days or 5 times the plasma half-life, or who have previously participated in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aqueous Humour Concentration of Levofloxacin | 90±15 min after the first administration of the study treatments | Defined as the concentration of levofloxacin into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of levofloxacin has been measured by LC tandem mass spectrometry. |
| Aqueous Humour Concentration of Dexamethasone 21-phosphate | 90±15 min after the first administration of the study treatments | Defined as the concentration of dexamethasone 21-phosphate into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin. The concentration of dexamethasone 21-phosphate has been measured by LC tandem mass spectrometry. |
| Aqueous Humour Concentration of Dexamethasone | 90±15 min after the first administration of the study treatments | Defined as the concentration of dexamethasone into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of dexamethasone has been measured by LC tandem mass spectrometry. |
Countries
Italy
Participant flow
Recruitment details
Study Period: * Date of first enrolment: 4 September 2018 * Date study finalized (last patient last visit): 6 December 2018 Study centres: * U.O. Oculistica Universitaria, Azienda Ospedaliera Universitaria Pisana, Presidio Ospedaliero di Cisanello, Pisa; * Clinica Oculistica, Presidio Ospedale San Paolo, Milan.
Pre-assignment details
Planned sample size n.120; randomized patients n.125; screened patients n.133 (1 patient screened for both eyes).
Participants by arm
| Arm | Count |
|---|---|
| Levofloxacin + Dexamethasone Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone.
Administration route: ocular instillation
Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP). | 42 |
| Levofloxacin Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin.
Administration route: ocular instillation
Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin). | 42 |
| Dexamethasone Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone.
Administration route: ocular instillation
Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP). | 41 |
| Total | 125 |
Baseline characteristics
| Characteristic | Levofloxacin | Dexamethasone | Total | Levofloxacin + Dexamethasone |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 35 Participants | 108 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 17 Participants | 7 Participants |
| Age, Continuous | 75.38 years STANDARD_DEVIATION 8.38 | 74.59 years STANDARD_DEVIATION 8 | 74.14 years STANDARD_DEVIATION 8.03 | 72.45 years STANDARD_DEVIATION 7.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 40 Participants | 122 Participants | 42 Participants |
| Region of Enrollment Italy | 42 participants | 41 participants | 125 participants | 42 participants |
| Sex: Female, Male Female | 21 Participants | 21 Participants | 69 Participants | 27 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 56 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 42 | 0 / 41 |
| other Total, other adverse events | 0 / 42 | 0 / 42 | 1 / 41 |
| serious Total, serious adverse events | 0 / 42 | 0 / 42 | 0 / 41 |
Outcome results
Primary
Aqueous Humour Concentration of Dexamethasone
Defined as the concentration of dexamethasone into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of dexamethasone has been measured by LC tandem mass spectrometry.
Time frame: 90±15 min after the first administration of the study treatments
Population: Participants in all Arms/Groups were assessed for this Outcome Measure regardless of treatment type
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Levofloxacin + Dexamethasone | Aqueous Humour Concentration of Dexamethasone | 0.030 nmol/mL |
| Levofloxacin | Aqueous Humour Concentration of Dexamethasone | 0 nmol/mL |
| Dexamethasone | Aqueous Humour Concentration of Dexamethasone | 0.042 nmol/mL |
Primary
Aqueous Humour Concentration of Dexamethasone 21-phosphate
Defined as the concentration of dexamethasone 21-phosphate into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin. The concentration of dexamethasone 21-phosphate has been measured by LC tandem mass spectrometry.
Time frame: 90±15 min after the first administration of the study treatments
Population: Participants in all Arms/Groups were assessed for this Outcome Measure regardless of treatment type
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Levofloxacin + Dexamethasone | Aqueous Humour Concentration of Dexamethasone 21-phosphate | 0 nmol/mL |
| Levofloxacin | Aqueous Humour Concentration of Dexamethasone 21-phosphate | 0 nmol/mL |
| Dexamethasone | Aqueous Humour Concentration of Dexamethasone 21-phosphate | 0 nmol/mL |
Primary
Aqueous Humour Concentration of Levofloxacin
Defined as the concentration of levofloxacin into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of levofloxacin has been measured by LC tandem mass spectrometry.
Time frame: 90±15 min after the first administration of the study treatments
Population: Participants in all Arms/Groups were assessed for this Outcome Measure regardless of treatment type
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Levofloxacin + Dexamethasone | Aqueous Humour Concentration of Levofloxacin | 1.970 nmol/mL |
| Levofloxacin | Aqueous Humour Concentration of Levofloxacin | 2.151 nmol/mL |
| Dexamethasone | Aqueous Humour Concentration of Levofloxacin | 0 nmol/mL |