NSAID vs Steroid-NSAID Combo for Glaucoma

(CES-NSLT Trial)

Overseen By Sharan Bains, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: St. Joseph's Healthcare Hamilton

Must not be taking: Systemic ketorolac, Fluorometholone

Disqualifiers: Other ocular disorders, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 week

126 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial, led by Dr. Enitan A. Sogbesan at the Hamilton Regional Eye Clinic, St. Joseph's Healthcare Hamilton, aims to compare the efficacy and safety of non-steroidal anti-inflammatory drug (NSAID) ketorolac alone versus a combination of ketorolac and the corticosteroid fluorometholone, and a control group receiving no postoperative treatment. The trial will evaluate these treatment strategies following Selective Laser Trabeculoplasty (SLT) in patients with open-angle glaucoma. The primary objective is to determine the most effective postoperative management strategy to reduce inflammation, improve patient comfort, and control intraocular pressure (IOP). Participants will be randomly assigned to one of the three groups, with follow-up visits scheduled at 1 hour, 1 week, 1 month, 3 months, 6 months, and 1 year post-SLT. The study's findings aim to guide clinicians in optimizing postoperative care for better patient outcomes.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination of NSAID and Steroid-NSAID for treating glaucoma?

Research shows that ketorolac tromethamine, a component of the treatment, is effective in reducing inflammation after eye surgeries like cataract surgery, which suggests it may help manage inflammation in glaucoma treatment as well. ^{1 2 3 4 5}

Is the NSAID Ketorolac safe for use in humans?

Ketorolac tromethamine, used in eye drops for inflammation after cataract surgery, has been studied for safety and is approved by the U.S. Food and Drug Administration for this purpose. It is also used for pain control after surgeries, though there is some concern about increased risk of bleeding in certain surgeries. ^{2 6 7 8 9}

How is the drug ketorolac different from other treatments for glaucoma?

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that can reduce inflammation without the risk of worsening viral infections, unlike corticosteroids. It is typically used in eye drop form to manage inflammation after eye surgeries, making it a unique option for treating inflammation in glaucoma patients. ^{2 7 10 11 12}

Research Team

Enitan A Sogbesan, MD

Principal Investigator

St. Joseph's Healthcare Hamilton

Eligibility Criteria

This trial is for patients with open-angle glaucoma who have undergone Selective Laser Trabeculoplasty (SLT). They should not be receiving any postoperative treatment currently. The study excludes individuals who cannot follow the visit schedule or have conditions that might interfere with the drug's effects.

Inclusion Criteria

I am 18 years old or older.

I have been diagnosed with open-angle glaucoma.

Intraocular pressure (IOP) greater than 16 mmHg on at least two consecutive occasions separated by one month

Exclusion Criteria

Patients who are unable to speak/understand English

I haven't had eye disorders or surgeries in the last 6 months.

Allergy or intolerance to ketorolac or fluorometholone

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ketorolac alone, a combination of ketorolac and fluorometholone, or no treatment following Selective Laser Trabeculoplasty (SLT)

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in intraocular pressure, visual acuity, anterior chamber inflammation, and patient-reported discomfort

1 year

6 visits (in-person) at 1 hour, 1 week, 1 month, 3 months, 6 months, and 1 year post-SLT

Treatment Details

Interventions

• Fluorometholone
• Ketorolac

Trial Overview The trial tests how effective and safe an NSAID eye drop, Ketorolac, is alone versus combined with a steroid, Fluorometholone, after SLT surgery. Patients are randomly placed in one of three groups: Ketorolac only, combination drops, or no treatment.

Participant Groups

Group I: Ketorolac with Fluorometholone Experimental Treatment 1 Intervention

Participants in this arm will receive a combination of ketorolac 0.5% eye drops administered twice daily and fluorometholone 0.1% eye drops administered four times daily for one week following Selective Laser Trabeculoplasty (SLT). Fluorometholone is a corticosteroid that reduces inflammation by stabilizing capillary permeability and inhibiting inflammatory cell activation. This arm aims to evaluate the combined efficacy and safety of ketorolac and fluorometholone in postoperative care.

Group II: Ketorolac Alone Experimental Treatment 1 Intervention

Participants in this arm will receive ketorolac 0.5% eye drops administered twice daily for one week following Selective Laser Trabeculoplasty (SLT). Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that helps reduce inflammation and alleviate pain. The purpose of this intervention is to assess the efficacy and safety of ketorolac alone in managing postoperative inflammation and patient comfort compared to other treatment strategies.

Group III: No Treatment Control Active Control 1 Intervention

Participants in this arm will not receive any postoperative treatment following Selective Laser Trabeculoplasty (SLT). This control group is included to provide a baseline for comparison against the treatment groups receiving ketorolac alone or a combination of ketorolac and fluorometholone. The purpose is to assess the natural course of postoperative inflammation and patient comfort without intervention.

Ketorolac is already approved in United States, European Union, Switzerland for the following indications:

Approved in United States as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea
• Idiopathic pericarditis
• Ocular itching

Approved in European Union as Toradol for:

• Moderate to severe pain
• Postoperative pain
• Dysmenorrhea

Approved in United States as Acular for:

• Ocular itching
• Inflammation after eye surgery

Approved in United States as Sprix for:

• Moderate to severe pain

Approved in Switzerland as Ketorolac for:

• Moderate to severe pain
• Postoperative pain

Who Is Running the Clinical Trial?

St. Joseph's Healthcare Hamilton

Lead Sponsor

Trials

203

Recruited

26,900+

Findings from Research

In a multicenter study involving patients with moderate to severe inflammation after cataract surgery, ketorolac tromethamine 0.5% was significantly more effective than a placebo in reducing inflammation and associated symptoms like pain and photophobia.

The treatment was found to be safe, with no significant differences in visual acuity or adverse events compared to the placebo, indicating that ketorolac is a reliable option for managing post-surgical inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. Heier, J., Cheetham, JK., Degryse, R., et al.[2019]

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

In a study involving 15 rabbits, intraocular injections of preservative-free ketorolac tromethamine showed no significant adverse effects on retinal function or intraocular pressure compared to control eyes, indicating its safety for use.

The drug had a short elimination half-life of 2.3 hours in the vitreous, and no histopathological changes were observed, suggesting that ketorolac could be a viable alternative to steroid injections for treating intraocular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of intraocular ketorolac in rabbits. Margalit, E., Kugler, LJ., Brumm, MV., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Can topical ketorolac 0.5% improve the function of Ahmed® glaucoma drainage devices? [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of preoperative versus postoperative ketorolac tromethamine 0.5% in reducing inflammation after cataract surgery. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Intravitreal injection of commercially available ketorolac tromethamine in eyes with diabetic macular edema refractory to laser photocoagulation. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Preoperative ketorolac tromethamine 0.4% in phacoemulsification outcomes: pharmacokinetic-response curve. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of nonpreserved ketorolac tromethamine ophthalmic solution following radial keratotomy. Ketorolac Radial Keratotomy Study Group. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Comparative effects of ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions on inflammation after cataract surgery. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The safety of intraocular ketorolac in rabbits. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Effect of ketorolac on herpes simplex virus type one ocular infection in rabbits. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of ketorolac tromethamine 0.5% and prednisolone acetate 1% after cataract surgery. [2019]

12. New Zealand pubmed.ncbi.nlm.nih.gov

A review of the use of ketorolac tromethamine 0.4% in the treatment of post-surgical inflammation following cataract and refractive surgery. [2022]