Levo-Dexa vs. Tobra+Dexa for Prevention and Treatment of Inflammation and Prevention of Infection in Cataract Surgery (LEADER7)

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

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.

Study Overview

• Status: Completed
• Conditions: Cataract
• Intervention / Treatment: Drug: Levofloxacin + dexamethasone followed by dexamethasone; Drug: Tobramycin + Dexamethasone

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 Type: Interventional
• Enrollment (Actual): 808
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Az. Osp. di Rilievo Nazionale "A. Cardarelli" di Napoli
  • Novara, Italy, 28100
    • A.O.U. "Maggiore della Carità" di Novara
  • Siena, Italy, 53100
    • A.O.U. Senese - Università degli Studi di Siena
  • AN
    • Ancona, AN, Italy, 60126
      • A.O.U. Osp. Riuniti Umberto I - G.M. Lancisi - G. Salesi - Università degli Studi di Ancona
  • BA
    • Altamura, BA, Italy, 70022
      • Ospedale della Murgia "Fabio Perinei" di Altamura
    • Bari, BA, Italy, 70125
      • A.O.U. Policlinico Consorziale di Bari
    • Bari, BA, Italy, 70131
      • ASL Bari - Ospedale "Di Venere" - Carbonara di Bari
  • BG
    • Bergamo, BG, Italy, 24125
      • Cliniche Gavazzeni S.p.A. - Humanitas Gavazzeni di Bergamo
  • BO
    • Bologna, BO, Italy, 40138
      • A.O.U. di Bologna - Policlinico S. Orsola-Malpighi di Bologna
    • Bologna, BO, Italy, 40138
      • Policlinico S. Orsola-Malpighi di Bologna
  • BS
    • Brescia, BS, Italy, 25123
      • ASST degli Spedali Civili di Brescia - P.O. Spedali Civili di Brescia
    • Chiari, BS, Italy, 25032
      • ASST Franciacorta - P.O. di Chiari
  • CH
    • Chieti, CH, Italy, 66100
      • P.O. Ospedale Clinicizzato SS. Annunziata di Chieti
  • CO
    • Como, CO, Italy, 22100
      • Ospedale Valduce di Como
  • CT
    • Catania, CT, Italy, 95123
      • A.O.U. Policlinico Vittorio Emanuele - P.O. Gaspare Rodolico - Università degli Studi di Catania
    • Catania, CT, Italy, 95125
      • Policlinico G.B. Morgagni di Catania - Casa di Cura s.r.l.
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • A.O. Mater Domini di Catanzaro - Università degli Studi Magna Graecia di Catanzaro
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • IRCCS Casa Sollievo della Sofferenza di San Giovanni Rotondo
  • FI
    • Firenze, FI, Italy, 50139
      • A.O.U. Careggi di Firenze
  • GE
    • Genova, GE, Italy, 16132
      • IRCCS Ospedale Policlinico San Martino di Genova
    • Genova, GE, Italy, 16132
      • Ospedale Policlinico San Martino - Università degli Studi di Genova
  • LC
    • Erba, LC, Italy, 22036
      • Fatebenefratelli - Ospedale "Sacra Famiglia" di Erba
  • LU
    • Lido Di Camaiore, LU, Italy, 55049
      • Az. USL Toscana Nord Ovest - Ospedale della Versilia
    • San Filippo, LU, Italy, 56123
      • AUSL Toscana Nord Ovest - P.O. San Luca di Lucca
  • ME
    • Messina, ME, Italy, 98124
      • A.O.U. Policlinico "G. Martino" di Messina
    • Milazzo, ME, Italy, 98057
      • ASP di Messina - P.O. "Giuseppe Fogliani" di Milazzo
  • MI
    • Legnano, MI, Italy, 20025
      • ASST Ovest Milanese - Ospedale Civile di Legnano
    • Milano, MI, Italy, 20122
      • IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
    • Milano, MI, Italy, 20123
      • Gruppo Multimedica - Ospedale San Giuseppe di Milano
    • Milano, MI, Italy, 20132
      • Ospedale San Raffaele IRCCS S.r.l.
    • Milano, MI, Italy, 20157
      • ASST Fatebenefratelli Sacco - Università degli Studi di Milano - Ospedale L. Sacco
    • Rozzano, MI, Italy, 20089
      • IRCCS Istituto Clinico Humanitas di Rozzano
    • Vizzolo Predabissi, MI, Italy, 20077
      • ASST di Melegnano e della Martesana - Ospedale di Vizzolo Predabissi
  • MO
    • Modena, MO, Italy, 41125
      • A.O.U. Policlinico di Modena - Università degli Studi di Modena e Reggio Emilia
    • Sassuolo, MO, Italy, 41049
      • Ospedale Di Sassuolo
  • MS
    • Carrara, MS, Italy, 54033
      • Centro Polispecialistico Monterosso di Carrara
  • PA
    • Palermo, PA, Italy, 90127
      • A.O.U. Policlinico "P. Giaccone" di Palermo
    • Palermo, PA, Italy, 90146
      • A.O. "Ospedali Riuniti Villa Sofia-Cervello" di Palermo - P.O. "Villa Sofia" di Palermo
  • PC
    • Piacenza, PC, Italy, Piacenza
      • AUSL di Piacenza - Ospedale "Guglielmo da Saliceto" di Piacenza
  • PD
    • Padova, PD, Italy, 35100
      • Az. ULSS 6 Euganea - Ospedale S. Antonio - Centro Oculistico San Paolo di Padova
  • PD)
    • Monselice, PD), Italy, 35043
      • Az. ULSS 6 Euganea - Ospedali Riuniti Padova Sud - Ospedale Madre Teresa di Calcutta-Schiavonia
  • PG
    • Perugia, PG, Italy, 06156
      • A.O. di Perugia - Ospedale S. Maria della Misericordia di Perugia
  • PV
    • Pavia, PV, Italy, 27100
      • Fondazione IRCCS Policlinico S. Matteo - Università degli Studi di Pavia
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli di Reggio Calabria
  • RM
    • Roma, RM, Italy, 00128
      • Policlinico Universitario Campus Bio-Medico di Roma
    • Roma, RM, Italy, 00133
      • Fondazione PTV Policlinico Tor Vergata
    • Roma, RM, Italy, 00189
      • A.O.U. Sant'Andrea di Roma
    • Roma, RM, Italy, 00198
      • IRCCS Fondazione G.B. Bietti di Roma
  • RN
    • Civitavecchia, RN, Italy, 00053
      • ASL Roma 4 - Ospedale San Paolo di Civitavecchia
  • RO
    • Rovigo, RO, Italy, 45100
      • Az. ULSS 5 Polesana - Ospedale "Santa Maria della Misericordia"
  • TO
    • Torino, TO, Italy, 10126
      • A.O.U Città della Salute e della Scienza di Torino - Ospedale Molinette
  • TS
    • Trieste, TS, Italy, 34129
      • Az. Sanitaria Universitaria Integrata di Trieste - Ospedali Riuniti di Trieste - Ospedale Maggiore
  • TV
    • Treviso, TV, Italy, 31100
      • Az. ULSS 2 Marca Trevigiana - Ospedale di Treviso
  • UD
    • Udine, UD, Italy, 33100
      • Az. Sanitaria Universitaria Integrata di Udine - P.O. Universitario "Santa Maria della Misericordia" diUdine
  • VI
    • Bassano Del Grappa, VI, Italy, 36061
      • Az. ULSS 7 Pedemontana - Ospedale San Bassiano di Bassano del Grappa
  • VR
    • Negrar, VR, Italy, 37024
      • Ospedale Sacro Cuore - Don Calabria di Negrar
    • Verona, VR, Italy, 37134
      • A.O.U. Integrata di Verona - Ospedale Borgo Roma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria prior to surgery:

1. Signed written informed consent
2. Male or female, age ≥40 years
3. Scheduled senile or presenile cataract surgery
4. Willing to interrupt the use of contact lenses for the entire duration of the study
5. Able and willing to follow study procedures

6. Female patients must be postmenopausal, surgically sterile or must agree to use an effective method of contraception

   Inclusion criteria following surgery:

7. Surgery completed without complications

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Levofloxacin + dexamethasone followed by dexamethasone; 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.; Other Names: Levofloxacin + dexamethasone followed by Maxidex
Active Comparator: Tobramycin + dexamethasone; Tobramycin + dexamethasone (14 days, 1 drop/4 times a day).	Drug: Tobramycin + Dexamethasone; Tobramycin + dexamethasone ophthalmic suspension (Tobradex®) for 14 days, 1 drop - 4 times a day.; Other Names: Tobradex

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular Pressure (IOP)	IOP is measured using a tonometer. IOP is measured as mmHg; normal intraocular pressures average between 12-22 mm Hg.	At day 0 (screening) and at day 4, 8, 15
Visual Acuity	Visual acuity was assessed as per local clinical practice, i.e. with the Snellen (feet) or the ETDRS (meter) chart. Visual acuity was then analysed using decimal unit. Decimal score is the decimal expression of the Snellen (feet) or the ETDRS (meter) charts in which the numerator indicates the distance from the chart and the denominator indicates the size of the smallest line that can be read. Decimal values were provided directly from the investigator or computed as a result of the Snellen or ETDRS fraction. Generally decimal values from 0.01 to 0.10 indicate severe vision loss; decimal values from 0.125 to 0.25 indicate moderate vision loss; decimal values from 0.32 to 0.63 indicate mild vision loss; decimal values from 0.8 to 1.6 indicate normal vision. Lower decimal values correspond to a reduced visual acuity and worst outcomes, while higher decimal values indicate an improved visual acuity and better outcomes.	At day 0 (screening) and at day 15
Adverse Events	Adverse events were described according to System Organ Classes (SOC) and Preferred Terms (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) and were presented by treatment group.	During all the treatment until day 15
Global Evaluation of Local Tolerability	Global evaluation was evaluated on a 4-point scale: 0 = no intolerability, 1 = mild intolerability, 2 = moderate intolerability, 3 = maximum intolerability.	Day 4, 8, 15
Burning, Stinging, Blurred Vision	Burning, stinging, blurred vision were evaluated on a 4-point scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe.	Day 4, 8, 15
Assessment of Patient Diary (Compliance)	Treatment compliance is derived from the number of instillations each day during the study treatment exposure	Day 15

Collaborators and Investigators

• Sponsor: NTC srl
• Investigators: Principal Investigator: Francesco Bandello, Prof., Ospedale San Raffaele IRCCS S.r.l.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): December 19, 2018

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Lens Diseases; Inflammation; Cataract; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Pharmaceutical Solutions; Cytochrome P-450 CYP1A2 Inhibitors; Ophthalmic Solutions; Anti-Infective Agents, Urinary; Renal Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Levofloxacin; Ofloxacin; Tobramycin; Tobramycin, Dexamethasone Drug Combination
• Other Study ID Numbers: LEVODESA_04-2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No