Levo-Dexa vs. Tobra+Dexa for Prevention and Treatment of Inflammation and Prevention of Infection in Cataract Surgery

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the non-inferiority of the study treatment (combined levofloxacin + dexamethasone eye drops) followed by dexamethasone eye drops alone vs. standard treatment in the prevention and treatment of postoperative ocular inflammation and prevention of infection.

Detailed Description
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In clinical practice, topical treatment following cataract surgery is frequently administered using a combination between an antibiotic and a corticosteroid to promote patient adherence to therapy and to obtain both prevention of infection and treatment of post-surgical inflammation. The combination of tobramycin and dexamethasone is among the most widely used combinations, however, treatment duration and the need for tapering posology over several weeks may favour the development of bacterial 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 evaluate the non-inferiority of the study treatment, used for a limited period of time and followed by dexamethasone alone, compared to standard treatment in preventing and treating ocular inflammation and in preventing post-operative infection while limiting the emergence of antibiotic resistance.

Official Title
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An International, Multicenter, Randomized, Blinded-assessor, Parallel-group Clinical Study Comparing Eye Drops of Combined LEvofloxAcin + DExamethasone foR 7 Days Followed by Dexamethasone Alone for an Additional 7 Days vs. Tobramycin + Dexamethasone for 14 Days for the Prevention and Treatment of Inflammation and Prevention of Infection Associated With Cataract Surgery in Adults - LEADER 7

Conditions
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Cataract

Intervention / Treatment
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* Drug: Levofloxacin + dexamethasone followed by dexamethasone
* Drug: Tobramycin + Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria prior to surgery: Signed written informed consent Male or female, age ≥40 years Scheduled senile or presenile cataract surgery Willing to interrupt the use of contact lenses for the entire duration of the study Able and willing to follow study procedures Female patients must be postmenopausal, surgically sterile or must agree to use an effective method of contraception Inclusion criteria following surgery: Surgery completed without complications Exclusion Criteria: Ocular conditions that at the discretion of the Investigator may interfere with the efficacy and/or safety evaluations Patients undergoing bilateral cataract surgery Patients under treatment with prostaglandin analogues or intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs Systemic diseases that may interfere with the results of the study Any condition that could interfere with correct instillation of eye drops Ocular surgery in the study eye (including laser surgery) in the 3 months before screening Monocular patients Visual Acuity < 20/80 of the contralateral eye measured as ETDRS or Snellen Contraindications to ocular treatment with Tobradex®, Maxidex® or levofloxacin/dexamethasone Hypersensitivity to the study product or its excipients Participation in other clinical studies within at least 5 half-lives of the Investigational Medicinal Product (IMP) used in the previous studies Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, parallel-group study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levofloxacin + Dexamethasone followed by dexamethasone<br>Levofloxacin 5 mg/ml+Dexamethasone 1 mg/ml (7 days,1 drop/4 times a day) followed by dexamethasone 1 mg/ml (7 days,1 drop/4 times a day). | Drug: Levofloxacin + dexamethasone followed by dexamethasone<br>* Levofloxacin + dexamethasone ophthalmic solution for 7 days, 1 drop - 4 times a day, followed by dexamethasone ophthalmic suspension (Maxidex®) for an additional 7 days, 1 drop - 4 times a day.<br>* Other names: Levofloxacin + dexamethasone followed by Maxidex;|
| Active Comparator: Tobramycin + dexamethasone<br>Tobramycin + dexamethasone (14 days, 1 drop/4 times a day). | Drug: Tobramycin + Dexamethasone<br>* Tobramycin + dexamethasone ophthalmic suspension (Tobradex®) for 14 days, 1 drop - 4 times a day.<br>* Other names: Tobradex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Without Signs of Anterior Chamber Inflammation | The number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). The following non-inferiority hypotheses has been tested: H0 : πT - πS ≤ - Δ; H1 : πT - πS > - Δ. Where πT and πS are the number of participants without signs of anterior chamber inflammation in the test and standard treatments, respectively, and the non-inferiority margin is Δ = 10%. | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Endophthalmitis | The number of participants with endophthalmitis after administration of study treatment in the study was assessed and reported. Diagnosis of endophthalmitis is based on clinical evaluation of signs and symptoms (such as swollen eyelids, ocular pain, conjunctival hyperemia, decreased visual acuity, opaque vitreous) through slit lamp examination, and microbiological tests on conjunctival or corneal swabs. | Day 4, 8, 15 | 
| Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). | Day 0 (screening), 4, 8 | 
| Conjunctival Hyperemia | Conjunctival hyperemia was evaluated with slit lamp and results provided as a score as follows: 0 = absence of inflammation, 1 = mild inflammation (some vessels injected), 2 = moderate inflammation (diffuse injection of vessels, but individual vessels are still discernable) 3 = severe inflammation (intense injection of vessels, individual vessels not easily discernable). | Day 4, 8, 15 | 
| Total Ocular Symptoms Score (TOSS) | The TOSS is a patient-reported evaluation in the TOSS Questionnaire of 3 ocular symptoms: itching/burning, hyperemia of conjunctiva and tearing. A score was given in the presence of symptoms: 0 = none, 1 = mild, 2 = moderate, 3 = severe. | Day 4, 8, 15 | 
| Ocular Pain/Discomfort: 4-point Scale | Overall ocular pain and discomfort was evaluated by the subject on a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). | Day 4, 8, 15 | 
| Use of Rescue Therapy | All rescue therapy used following cataract surgery is to be reported at all visits. | During all the treatment until day 15 |