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.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04685538

Enrollment

338

Registered

2020-12-28

Start date

2020-09-09

Completion date

2021-03-09

Last updated

2023-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cataract

Keywords

Cataract, Eye, Chloroprocaine

Brief summary

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

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.

Interventions

DRUGChloroprocaine 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.

DRUGTetracaine 0.5%

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants in Each Treatment Group With a Successful Surface Anesthesia	Before Intra Ocular Lens (IOL) implantation surgery.	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)

Secondary

Measure	Time frame	Description
Objective Ocular Signs	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	\- 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
Fluoresceine	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	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).
Endothelial Cell Counts	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	Modification of the basal status of the Endothelial cell counts evaluated with the specular microscopy
Corneal Thickness	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	Modification of the basal status of the assesment (Corneal thickness). Measurement of the central corneal thickness was to be performed with a pachymeter
Changes in Ocular Symptoms	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	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
Number of Participants With Abnormalities of the Retina, Macula, or Optic Nerve by Fundoscopy	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	Modification of the basal status of the assesment. Dilated fundus examination on retina, macula, optic nerve.
Intra-ocular Pressure	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	Modification of the basal status of the assesment. Intraocular pressure (in mmHg) was assessed according to site current practice (air puff or applanation tonometer).
Surgeon Satisfaction	day 1 - visit2 (Inclusion visit/Surgery)	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.
Patient Global Satisfaction	day 1 - visit2 (Inclusion visit/Surgery) after the treatment	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.
Best Far Corrected Visual Acuity	Visit 1 (Day -90/Day -1) and Visit 4 (Day 8 ± 1 day), up to approximately 102 days	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.

Countries

Italy, Slovakia, Spain

Participant flow

Recruitment details

In total, 410 subjects were screened in the study, 64 of which were dropped as screen failure and 346 were randomised to receive a treatment. From the 346 subjects randomised, 338 were treated and received the drug that was assigned at the randomization procedure, while 8 discontinued before treatment. Eventually, 335 subjects completed the study since discontinuation issues occurred for three subjects, one due to an AE and two lost to follow-up

Participants by arm

Arm	Count
Chloroprocaine 3% All the eligible patients will be administrated by Chloroprocaine 3 % according to the randomization criteria. 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.	167
Tetracaine 0.5% All the eligible patients will be administrated by Tetracaine 0.5% according to the randomization criteria. 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.	171
Total	338

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Lost to Follow-up	0	2

Baseline characteristics

Characteristic	Chloroprocaine 3%	Tetracaine 0.5%	Total
Age, Continuous	70.3 years STANDARD_DEVIATION 10.3	68.8 years STANDARD_DEVIATION 9.9	69.9 years STANDARD_DEVIATION 10.1
Race and Ethnicity Not Collected	—	—	0 Participants
Sex: Female, Male Female	94 Participants	86 Participants	180 Participants
Sex: Female, Male Male	73 Participants	85 Participants	158 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 167	0 / 171
other Total, other adverse events	14 / 167	19 / 171
serious Total, serious adverse events	0 / 167	0 / 171

Outcome results

Primary

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)

Time frame: Before Intra Ocular Lens (IOL) implantation surgery.

Arm	Measure	Group	Value (NUMBER)
Chloroprocaine 3%	Number of Participants in Each Treatment Group With a Successful Surface Anesthesia	Anesthesia Success	153 participants
Chloroprocaine 3%	Number of Participants in Each Treatment Group With a Successful Surface Anesthesia	Anesthesia NO Success	14 participants
Tetracaine 0.5%	Number of Participants in Each Treatment Group With a Successful Surface Anesthesia	Anesthesia Success	152 participants
Tetracaine 0.5%	Number of Participants in Each Treatment Group With a Successful Surface Anesthesia	Anesthesia NO Success	19 participants

Secondary

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.