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

Cataract Clinical Trial

— LEADER7  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03739528
• Other study ID #: LEVODESA_04-2017
• Status: Completed
• Phase: Phase 3
• Start date: September 3, 2018
• Est. completion date: December 19, 2018

Study information

• Verified date: August 2020
• Source: NTC srl
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 808
• Est. completion date: December 19, 2018
• Est. primary completion date: December 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cataract
• Inflammation

Intervention

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.
• Tobramycin + Dexamethasone
Tobramycin + dexamethasone ophthalmic suspension (Tobradex®) for 14 days, 1 drop - 4 times a day.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
NTC srl

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Assessment of Patient Diary (Compliance)	Treatment compliance is derived from the number of instillations each day during the study treatment exposure	Day 15
Primary	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 : pT - pS = - ?; H1 : pT - pS > - ?. Where pT and pS are the number of participants without signs of anterior chamber inflammation in the test and standard treatments, respectively, and the non-inferiority margin is ? = 10%.	Day 15
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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