Chloroprocaine 3% Gel Eye Drop as Topical Anestheticsin Phacoemulsification.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Cataract

Intervention / Treatment
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* Drug: Chloroprocaine 3%
* Drug: Tetracaine 0.5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Male or female aged≥ 18 years Senile or pre-senile cataract 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: Combined surgery Previous intraocular surgery Previous corneal refractive surgeries less than 6 months before screening Non Senile or non pre-senilecataract (e.g.: traumatic, pathological or congenital cataract) Pupillary abnormalities (irregular, etc.) Iris synechiae Eye movement disorder (nystagmus, etc.) Dacryocystitis and all other pathologies of tears drainage system History of Inflammatory ocular disease (Iritis, uveitis, herpetic keratitis) Corneal, epithelial, stromal or endothelial, residual or evolutionary disease (including corneal ulceration and superficial punctuate keratitis) History of ocular traumatism, infection or inflammation within the last 3 months Pseudo-exfoliation, exfoliative syndrome Prior intravitreal injections within 7 days of the surgery IOP over 25mmHg under treatment Best corrected visual acuity < 1/10 Patient already included in the study for phakoexeresis History of ophthalmic surgical complication (cystoid macular oedema, etc.) Diabetes mellitus Surdity Pakinsondisease Excessive anxiety 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. Known hypersensitivity to sulfonamides products or any of the components of the study medications or to test products Specific exclusion criteria for women Pregnancy (positive pregnancy test), lactation 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 Women not hysterectomized, not menopaused nor surgically sterilized. Exclusion criteria related to general conditions Inability of patient and/or relatives to understand the study procedures and thus inability to give informed consent Non-compliant patient and/or relatives (e.g. not willing to attend the follow-up visits, way of life interfering with compliance) Participation in anotherclinicalstudy Already included once in this study Ward of court Patient not covered by the Social Security

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroprocaine 3%<br>All the eligible patients will be administrated by Chloroprocaine 3 % according to the randomization criteria. | Drug: Chloroprocaine 3%<br>* 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.<br>* Other names: Arm 1;|
| Active Comparator: Tetracaine 0.5%<br>All the eligible patients will be administrated by Tetracaine 0.5% according to the randomization criteria. | Drug: Tetracaine 0.5%<br>* 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.<br>* Other names: Arm 2;|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cataract, Eye, Chloroprocaine