Chloroprocaine 3% Gel Eye Drop as Topical Anestheticsin Phacoemulsification.

A Prospective, Observer-masked, Randomized Clinical Trial to Investigate and Compare the Clinical Efficacy of Chloroprocaine 3% Gel and Tetracaine 0.5% Eye Drop as Topical Anestheticsin Phacoemulsification.

Randomized clinical trial, multicenter, two-armed, to investigate and compare the clinical efficacy of chloroprocaine 3% gel and tetracaine 0.5% eye drop as topical anestheticsin phacoemulsification. This prospective, observer masked, randomised, controlled, equivalence phase 3 study will be conducted in approximately 4 European Countries. Sintetica intends to perform a phase 3 study on patients undergoing cataract surgery to assess the safety and efficacy of topical anaesthesia using chloroprocaine gel.

Study Overview

• Status: Completed
• Conditions: Cataract
• Intervention / Treatment: Drug: Chloroprocaine 3%; Drug: Tetracaine 0.5%

Detailed Description

Prospective,randomized, multi-center, active-controlled, masked-observer, parallel-group, competitive equivalence study. The study has been designed to assess the equivalence of chloroprocaine 3% gel (Test) with respect to tetracaine 0.5% solution (Reference) in surface anesthesia. Patients in both groups will receive three drops of study products before surgery. The study will include a Selection visit (Day -90/Day -1), an Inclusion visit (Day 1/surgery day), a Follow-up visit (Day 2, phone visit), a Final visit (Day 8), and a Follow-up phone call - Optional (Day 28, phone visit).

Selection visit (Visit 1, Day -90/Day -1):

Patients scheduled to undergo cataract surgery in a single eye will be informed about the aims, procedures and possible risks of the study and will be asked to sign the informed consent form for the inclusion in the trial.

Inclusion visit/Surgery (Visit 2, Day 1):

Before the anesthesia, patients will be questioned about previous and concomitant ocular and non-ocular treatments. Inclusion /exclusion criteria and patient status will be verified. Patients will be randomized to either chloroprocaine 3% gel (Test) or tetracaine 0.5% eye drop (Reference) treatment group.

Follow-up visit/phone visit (Visit 3, Day 2):

Concomitant ocular and non-ocular treatments, AEs, and patient global satisfaction will be assessed.

Final visit (Visit 4, Day 8 ± 1 day):

Concomitant ocular and non-ocular treatments, ocular symptoms, best far corrected visual acuity in both eyes, endothelial cell count, corneal thickness, blood pressure and heart rate, and AEs will be assessed. Slit lamp examination and fluorescein test, IOP in both eyes, and fundoscopy will be performed.

Optional visit/phone visit (Visit 5, Day 28 ± 3 days):

Concomitant ocular and non-ocular treatments and AEs resolution will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Malpighi - Dipartimento testa collo, U.O. Oftalmologia Ciardella
  • Catanzaro, Italy, 88100
    • A.O. Mater Domini di Catanzaro - U.O. Oculistica
  • Firenze, Italy, 50134
    • A.O.U. Careggi di Firenze - Dipartimento neuromuscoloscheletrico e organi di senso, reparto di oculistica
  • Milano, Italy, 20122
    • "IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano" - Dipartimento di chirurgia, U.O. Oculistica
  • Milano, Italy, 20123
    • Gruppo Multimedica Ospedale San Giuseppe di Milano - Clinica oculistica
  • Milano, Italy, 20123
    • Ospedale San Raffaele IRCCS - Clinica oculistica
  • Milano, Italy, 20142
    • ASST Santi Paolo e Carlo - Presidio Ospedale San Paolo - Dipartimento testa collo, reparto di oculistica
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico S. Matteo - Dipartimento di scienze chirurgiche, U.O. Oculistica
  • Perugia, Italy, 06129
    • A.O. di Perugia - Ospedale S. Maria della Misericordia di Perugia - Clinica oculistica
  • Pisa, Italy, 56126
    • A.O.U. Pisana - Cisanello - D.A.I. Specialità chirurgiche, U.O. Oculistica
  • Roma, Italy, 00128
    • Policlinico Universitario Campus Bio-medico di Roma - U.O.C. Oftalmologia
  • Roma, Italy, 00133
    • Fondazione PTV Policlinico Tor Vergata - Dipartimento benessere della salute mentale e neurologica, dentale e degli organi di senso, U.O.S.D. Oculistica
  • Roma, Italy, 00136
    • Ospedale Oftalmico di Roma (ASL Roma 1) - Dipartimento di oculistica e rete oftalmologica
  • Roma, Italy, 00198
    • IRCCS Fondazione G.B. Bietti di Roma - U.O.S. Segmento anteriore con annessi oculari
  • Siena, Italy, 53100
    • A.O.U. Senese - Università degli Studi di Siena - Dipartimento della salute mentale e degli organi di senso, U.O.C. Oculistica
  • Udine, Italy, 33100
    • Az. Sanitaria Universitaria Integrata di Udine - P.O. Universitario "Santa Maria della Misericordia" - Dipartimento di chirurgia specialistica, clinica oculistica
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • Izak Vision Center s.r.o.
  • Banská Bystrica, Slovakia, 975 17
    • FNsP F. D. Roosevelta Banská Bystrica II. Očná klinika SZU
  • Bratislava, Slovakia, 821 03
    • ROBIN LOOK spol. s r.o., Centrum mikrochirurgie oka
  • Bratislava, Slovakia, 821 08
    • VESELY Očná Klinika, s.r.o.
  • Košice, Slovakia, 040 11
    • 3F s.r.o. Očná ambulancia a optika
  • Martin, Slovakia, 036 01
    • Uvea Klinika, S.R.O.
  • Trenčín, Slovakia, 911 08
    • VIDISSIMO s. r. o. Očná klinika
  • Žilina, Slovakia, 012 07
    • Fakultná nemocnica s poliklinikou Žilina Očné oddelenie
• Spain
  • Alicante, Spain, 03016
    • Vissum alicante
  • Barcelona, Spain, 08017
    • Instituto Oftalmológico Integral Servicio de Oftalmología Admiravisión en Clínica Corachan
  • Cadiz
    • Jerez de la Frontera, Cadiz, Spain, 11408
      • Oftalvist Cio Jerez Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed and dated informed consent
2. Male or female aged≥ 18 years
3. Senile or pre-senile cataract
4. Scheduled to undergo cataract surgery in a single eyeat a time (clear corneal self-sealing incisions - phacoemulsification - foldable intra-ocular lens surgery with injector)

Exclusion Criteria:

1. Combined surgery
2. Previous intraocular surgery
3. Previous corneal refractive surgeries less than 6 months before screening
4. Non Senile or non pre-senilecataract (e.g.: traumatic, pathological or congenital cataract)
5. Pupillary abnormalities (irregular, etc.)
6. Iris synechiae
7. Eye movement disorder (nystagmus, etc.)
8. Dacryocystitis and all other pathologies of tears drainage system
9. History of Inflammatory ocular disease (Iritis, uveitis, herpetic keratitis)
10. Corneal, epithelial, stromal or endothelial, residual or evolutionary disease (including corneal ulceration and superficial punctuate keratitis)
11. History of ocular traumatism, infection or inflammation within the last 3 months
12. Pseudo-exfoliation, exfoliative syndrome
13. Prior intravitreal injections within 7 days of the surgery
14. IOP over 25mmHg under treatment
15. Best corrected visual acuity < 1/10
16. Patient already included in the study for phakoexeresis
17. History of ophthalmic surgical complication (cystoid macular oedema, etc.)
18. Diabetes mellitus
19. Surdity
20. Pakinsondisease
21. Excessive anxiety
22. Any other medical or surgical history, disorder or disease such as acute or chronic severe organic disease: hepatic, endocrine neoplasic, hematological diseases, severe psychiatric illness, relevant cardiovascular abnormalities (such as unstable angina, bradycardia, atrial fibrillation,uncontrolled hypertension: systolic blood pressure over 140 mm Hg, diastolic blood pressure over 90 mmHg) and/or any complicating factor or structural abnormality judged by the investigator to be incompatible with the study.
23. Known hypersensitivity to sulfonamides products or any of the components of the study medications or to test products Specific exclusion criteria for women
24. Pregnancy (positive pregnancy test), lactation
25. Women of childbearing potential without an acceptable effective method of contraception (oral contraceptive, intra-uterine device, subcutaneous contraceptive implant) until end of the study participation OR
26. Women not hysterectomized, not menopaused nor surgically sterilized. Exclusion criteria related to general conditions
27. Inability of patient and/or relatives to understand the study procedures and thus inability to give informed consent
28. Non-compliant patient and/or relatives (e.g. not willing to attend the follow-up visits, way of life interfering with compliance)
29. Participation in anotherclinicalstudy
30. Already included once in this study
31. Ward of court
32. Patient not covered by the Social Security

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chloroprocaine 3%; All the eligible patients will be administrated by Chloroprocaine 3 % according to the randomization criteria.	Drug: Chloroprocaine 3%; Administration: three IMP drops instillation as follow: 1st Drop instillation, then wait for 5 minutes; Eye Disinfection, then wait for 2 minutes; 2nd Drop instillation, then wait for 1 minute; 3rdDrop instillation, then wait for 1 minute; Start of Surgery.; Other Names: Arm 1
Active Comparator: Tetracaine 0.5%; All the eligible patients will be administrated by Tetracaine 0.5% according to the randomization criteria.	Drug: Tetracaine 0.5%; Administration: three IMP drops instillation as follow: 1st Drop instillation, then wait for 5 minutes; Eye Disinfection, then wait for 2 minutes; 2nd Drop instillation, then wait for 1 minute; 3rdDrop instillation, then wait for 1 minute; Start of Surgery.; Other Names: Arm 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants in Each Treatment Group With a Successful Surface Anesthesia	Τhe primary endpoint is the number of partecipants in each treatment group with a successful surface anesthesia, without any supplementation at the time point T4 (1 minute after the 3rd drop installation)	Before Intra Ocular Lens (IOL) implantation surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluoresceine	Modification of the basal status evaluated with fluorescein test Approximately 2-3 minutes following fluorescein instillation, corneal staining was to be evaluated in both eyes, using a slit lamp, based on the Oxford scale (grades of 0-5: 0 is normal, 5 is severe abnormal).	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Endothelial Cell Counts	Modification of the basal status of the Endothelial cell counts evaluated with the specular microscopy	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Corneal Thickness	Modification of the basal status of the assesment (Corneal thickness). Measurement of the central corneal thickness was to be performed with a pachymeter	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Best Far Corrected Visual Acuity	Modification of the basal status of the assesment evaluated by LogMAR (Logarithm of the Minimum Angle of Resolution). When using a LogMAR chart, visual acuity is scored with reference to the logarithm of the minimum angle of resolution, as the chart's name suggests. An observer who can resolve details as small as 1 minute of visual angle scores LogMAR 0, since the base-10 logarithm of 1 is 0; an observer who can resolve details as small as 2 minutes of visual angle (i.e., reduced acuity) scores LogMAR 0.3, since the base-10 logarithm of 2 is near-approximately 0.3; and so on.	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Intra-ocular Pressure	Modification of the basal status of the assesment. Intraocular pressure (in mmHg) was assessed according to site current practice (air puff or applanation tonometer).	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Surgeon Satisfaction	Evaluation of surgeon satisfaction. Surgeon satisfaction was assessed through the question "How do you consider the study product global tolerance?", at a scale (a score of 0 is the minimum value with the best outcome and 3 is the maximum value with the worst outcome): (0) Very satisfactory, (1) Satisfactory, (2) Not very satisfactory, (3) Unsatisfactory. It is recorded at V2 and filled in by the surgeon who had performed the study. It is measured at Visit 2.	day 1 - visit2 (Inclusion visit/Surgery)
Patient Global Satisfaction	Patient global satisfaction at D1 based on a 5-question questionnaire read by a masked observer. A question read by a masked observer assessed the patient satisfaction about the overall anesthesia during the surgery: "Overall, how satisfied are you with the topical study product used for your local anesthesia during your cataract surgery?" It was measured with 5 possible answers (Likert satisfaction scale): Very satisfied (0), Globally satisfied (1), Neither satisfied nor Unsatisfied (2), Globally unsatisfied (3), Very unsatisfied (4). It was measured at Visit 3.	day 1 - visit2 (Inclusion visit/Surgery) after the treatment
Changes in Ocular Symptoms	Changes in ocular symptoms (pain, irritation/burning/stinging, foreign body sensation) will be graded by the patients according to the following scale (0 is the minimum value and 3 is tha maximum value) (0 = absent, 1 = mild, 2 = moderate, 3 = severe) during the study on Visit 1-selection and on visit 4-final	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Objective Ocular Signs	- Objective ocular signs assessed by slit lamp examination, flare, and other objective ocular signs will be graded according to the following scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The minimum value is 0 and maximum value is 3	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days
Number of Participants With Abnormalities of the Retina, Macula, or Optic Nerve by Fundoscopy	Modification of the basal status of the assesment. Dilated fundus examination on retina, macula, optic nerve.	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days

Collaborators and Investigators

• Sponsor: Sintetica SA
• Investigators: Principal Investigator: Jorge Alio, MD, Vissum Alicante, Calle del Cabañal 1, 03016 Alicante, Spain

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2020
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 9, 2021

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Cataract; Eye; Chloroprocaine
• Additional Relevant MeSH Terms: Eye Diseases; Lens Diseases; Cataract; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Tetracaine; Chloroprocaine
• Other Study ID Numbers: CHL.3/01-2019/M

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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