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

Phase 3

Completed

• Conditions: Cataract
• Interventions: Drug: Levofloxacin + dexamethasone followed by dexamethasone; Drug: Tobramycin + Dexamethasone

• Registration Number: NCT03739528
• Lead Sponsor: NTC srl

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-09-03
• Study First Submitted: 2018-11-09
• Study First Submitted QC: 2018-11-13
• Study First Posted: 2018-11-14
• Primary Completion: 2018-12-19
• Study Completion: 2018-12-19
• Results First Submitted: 2020-05-29
• Status Verified: 2020-08
• Results First Submitted QC: 2020-08-04
• Last Update Submitted: 2020-08-04
• Results First Posted: 2020-08-18
• Last Update Posted: 2020-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 808

Inclusion Criteria

Not provided

Exclusion Criteria

1. Ocular conditions that at the discretion of the Investigator may interfere with the efficacy and/or safety evaluations
2. Patients undergoing bilateral cataract surgery
3. Patients under treatment with prostaglandin analogues or intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs
4. Systemic diseases that may interfere with the results of the study
5. Any condition that could interfere with correct instillation of eye drops
6. Ocular surgery in the study eye (including laser surgery) in the 3 months before screening
7. Monocular patients
8. Visual Acuity < 20/80 of the contralateral eye measured as ETDRS or Snellen
9. Contraindications to ocular treatment with Tobradex®, Maxidex® or levofloxacin/dexamethasone
10. Hypersensitivity to the study product or its excipients
11. Participation in other clinical studies within at least 5 half-lives of the Investigational Medicinal Product (IMP) used in the previous studies
12. Pregnancy or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Levofloxacin + Dexamethasone followed by dexamethasone	Levofloxacin + dexamethasone followed by dexamethasone	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).
Tobramycin + dexamethasone	Tobramycin + Dexamethasone	Tobramycin + dexamethasone (14 days, 1 drop/4 times a day).

Primary Outcome Measures

Name	Time	Method
Number of Participants Without Signs of Anterior Chamber Inflammation	Day 15	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%.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Without Signs of Anterior Ocular Chamber Inflammation	Day 0 (screening), 4, 8	Number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0).
Number of Participants With Endophthalmitis	Day 4, 8, 15	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.
Total Ocular Symptoms Score (TOSS)	Day 4, 8, 15	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.
Ocular Pain/Discomfort: 4-point Scale	Day 4, 8, 15	Overall ocular pain and discomfort was evaluated by the subject on a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe).
Use of Rescue Therapy	During all the treatment until day 15	All rescue therapy used following cataract surgery is to be reported at all visits.
Conjunctival Hyperemia	Day 4, 8, 15	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).

Trial Locations

Locations (57)

IRCCS Ospedale Policlinico San Martino di Genova; 🇮🇹 Genova, GE, Italy

A.O.U. di Bologna - Policlinico S. Orsola-Malpighi di Bologna; 🇮🇹 Bologna, BO, Italy

Ospedale Valduce di Como; 🇮🇹 Como, CO, Italy

Cliniche Gavazzeni S.p.A. - Humanitas Gavazzeni di Bergamo; 🇮🇹 Bergamo, BG, Italy

ASL Bari - Ospedale "Di Venere" - Carbonara di Bari; 🇮🇹 Bari, BA, Italy

ASST degli Spedali Civili di Brescia - P.O. Spedali Civili di Brescia; 🇮🇹 Brescia, BS, Italy

ASST Franciacorta - P.O. di Chiari; 🇮🇹 Chiari, BS, Italy

AUSL Toscana Nord Ovest - P.O. San Luca di Lucca; 🇮🇹 San Filippo, LU, Italy

A.O.U. Policlinico "G. Martino" di Messina; 🇮🇹 Messina, ME, Italy

Ospedale di Sassuolo; 🇮🇹 Sassuolo, MO, Italy

Az. ULSS 6 Euganea - Ospedale S. Antonio - Centro Oculistico San Paolo di Padova; 🇮🇹 Padova, PD, Italy

Ospedale Policlinico San Martino - Università degli Studi di Genova; 🇮🇹 Genova, GE, Italy

Centro Polispecialistico Monterosso di Carrara; 🇮🇹 Carrara, MS, Italy

Policlinico G.B. Morgagni di Catania - Casa di Cura s.r.l.; 🇮🇹 Catania, CT, Italy

Gruppo Multimedica - Ospedale San Giuseppe di Milano; 🇮🇹 Milano, MI, Italy

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli di Reggio Calabria; 🇮🇹 Reggio Calabria, RC, Italy

Az. Sanitaria Universitaria Integrata di Trieste - Ospedali Riuniti di Trieste - Ospedale Maggiore; 🇮🇹 Trieste, TS, Italy

A.O.U. "Maggiore della Carità" di Novara; 🇮🇹 Novara, Italy

A.O.U. Senese - Università degli Studi di Siena; 🇮🇹 Siena, Italy

Fatebenefratelli - Ospedale "Sacra Famiglia" di Erba; 🇮🇹 Erba, LC, Italy

ASST Ovest Milanese - Ospedale Civile di Legnano; 🇮🇹 Legnano, MI, Italy

IRCCS Istituto Clinico Humanitas di Rozzano; 🇮🇹 Rozzano, MI, Italy

Fondazione IRCCS Policlinico S. Matteo - Università degli Studi di Pavia; 🇮🇹 Pavia, PV, Italy

A.O.U. Sant'Andrea di Roma; 🇮🇹 Roma, RM, Italy

Az. ULSS 7 Pedemontana - Ospedale San Bassiano di Bassano del Grappa; 🇮🇹 Bassano Del Grappa, VI, Italy

IRCCS Fondazione G.B. Bietti di Roma; 🇮🇹 Roma, RM, Italy

ASL Roma 4 - Ospedale San Paolo di Civitavecchia; 🇮🇹 Civitavecchia, RN, Italy

Az. ULSS 2 Marca Trevigiana - Ospedale di Treviso; 🇮🇹 Treviso, TV, Italy

P.O. Ospedale Clinicizzato SS. Annunziata di Chieti; 🇮🇹 Chieti, CH, Italy

A.O. Mater Domini di Catanzaro - Università degli Studi Magna Graecia di Catanzaro; 🇮🇹 Catanzaro, CZ, Italy

IRCCS Casa Sollievo della Sofferenza di San Giovanni Rotondo; 🇮🇹 San Giovanni Rotondo, FG, Italy

A.O.U. Careggi di Firenze; 🇮🇹 Firenze, FI, Italy

A.O.U. Policlinico "P. Giaccone" di Palermo; 🇮🇹 Palermo, PA, Italy

ASST di Melegnano e della Martesana - Ospedale di Vizzolo Predabissi; 🇮🇹 Vizzolo Predabissi, MI, Italy

A.O.U. Policlinico di Modena - Università degli Studi di Modena e Reggio Emilia; 🇮🇹 Modena, MO, Italy

AUSL di Piacenza - Ospedale "Guglielmo da Saliceto" di Piacenza; 🇮🇹 Piacenza, PC, Italy

Az. ULSS 6 Euganea - Ospedali Riuniti Padova Sud - Ospedale Madre Teresa di Calcutta-Schiavonia; 🇮🇹 Monselice, PD), Italy

A.O. di Perugia - Ospedale S. Maria della Misericordia di Perugia; 🇮🇹 Perugia, PG, Italy

Policlinico Universitario Campus Bio-medico di Roma; 🇮🇹 Roma, RM, Italy

Fondazione PTV Policlinico Tor Vergata; 🇮🇹 Roma, RM, Italy

Az. Sanitaria Universitaria Integrata di Udine - P.O. Universitario "Santa Maria della Misericordia" diUdine; 🇮🇹 Udine, UD, Italy

Ospedale Sacro Cuore - Don Calabria di Negrar; 🇮🇹 Negrar, VR, Italy

A.O.U. Policlinico Consorziale di Bari; 🇮🇹 Bari, BA, Italy

A.O.U. Osp. Riuniti Umberto I - G.M. Lancisi - G. Salesi - Università degli Studi di Ancona; 🇮🇹 Ancona, AN, Italy

Ospedale della Murgia "Fabio Perinei" di Altamura; 🇮🇹 Altamura, BA, Italy

Policlinico S. Orsola-Malpighi di Bologna; 🇮🇹 Bologna, BO, Italy

A.O.U. Policlinico Vittorio Emanuele - P.O. Gaspare Rodolico - Università degli Studi di Catania; 🇮🇹 Catania, CT, Italy

Ospedale San Raffaele IRCCS S.r.l.; 🇮🇹 Milano, MI, Italy

IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano; 🇮🇹 Milano, MI, Italy

ASP di Messina - P.O. "Giuseppe Fogliani" di Milazzo; 🇮🇹 Milazzo, ME, Italy

Az. USL Toscana Nord Ovest - Ospedale della Versilia; 🇮🇹 Lido Di Camaiore, LU, Italy

ASST Fatebenefratelli Sacco - Università degli Studi di Milano - Ospedale L. Sacco; 🇮🇹 Milano, MI, Italy

A.O. "Ospedali Riuniti Villa Sofia-Cervello" di Palermo - P.O. "Villa Sofia" di Palermo; 🇮🇹 Palermo, PA, Italy

Az. ULSS 5 Polesana - Ospedale "Santa Maria della Misericordia"; 🇮🇹 Rovigo, RO, Italy

A.O.U Città della Salute e della Scienza di Torino - Ospedale Molinette; 🇮🇹 Torino, TO, Italy

Az. Osp. di Rilievo Nazionale "A. Cardarelli" di Napoli; 🇮🇹 Napoli, Italy

A.O.U. Integrata di Verona - Ospedale Borgo Roma; 🇮🇹 Verona, VR, Italy