Ketorolac Eye Drops for Diabetic Retinopathy

(INSPIRE Trial)

Overseen By Crystal Nicholson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stephen J. Kim, MD

Must not be taking: NSAIDs, Aspirin

Disqualifiers: Vitrectomy, Macular disease, Hypertension, others

Compensation: Varies

Number of Visits: 4

Duration: 1 year

164 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if regular use of ketorolac eye drops can reduce inflammation and slow down or prevent the worsening of Diabetic Retinopathy in adults with type II diabetes. Ketorolac has been shown to be effective in reducing inflammation and symptoms associated with eye allergies and after surgery.

Will I have to stop taking my current medications?

If you are currently using prescription systemic NSAIDs or regularly using nonprescription NSAIDs like aspirin, you will need to stop taking them to participate in this trial.

Is ketorolac 0.45% ophthalmic solution safe for use in humans?

Ketorolac 0.45% eye drops have been generally well tolerated in clinical trials for eye inflammation after cataract surgery, with fewer side effects than a placebo (a substance with no active drug). No specific side effect was more common with ketorolac than with the placebo. ^{1 2 3 4 5}

How does the drug Ketorolac 0.45% ophthalmic solution differ from other treatments for diabetic retinopathy?

Ketorolac 0.45% ophthalmic solution is unique because it is a non-steroidal anti-inflammatory drug (NSAID) administered as eye drops, offering a topical treatment option for diabetic retinopathy. This differs from traditional treatments like laser photocoagulation, which can be invasive and uncomfortable, and systemic drugs that affect the entire body. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Ketorolac 0.45% ophthalmic solution for diabetic retinopathy?

Ketorolac 0.45% eye drops have been shown to reduce inflammation and pain after cataract surgery, and they may help improve visual function in diabetic patients with macular edema (swelling in the eye) after certain treatments. This suggests that Ketorolac could potentially help with inflammation and visual outcomes in diabetic retinopathy. ^{1 2 4 11 12}

Research Team

Stephen J Kim, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults with type II diabetes and moderate Diabetic Retinopathy (DR), specifically those with an HbA1c ≥ 8. It's also for age-matched non-diabetics needing vitrectomy surgery without inflammation. Excluded are individuals with ocular trauma, certain eye conditions, high blood pressure, or using NSAIDs regularly.

Inclusion Criteria

I am an adult with type II diabetes.

I am 18 or older with type II diabetes, moderate NPDR, and HbA1c ≥ 8.

I am of similar age, don't have diabetes, and need surgery for a non-inflammatory eye condition.

Exclusion Criteria

I have a disease affecting the macula, blood vessels in the eye, or eye inflammation.

Aim 1 Diabetic Arm: Inability to comply with follow-up

Aim 2: Inability to comply with follow-up

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily topical application of ketorolac or placebo to study its effects on PGE2 and cytokine levels, and DR progression

1 year

Visits every 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression of DR and DME

2 years

Treatment Details

Interventions

• Ketorolac 0.45% ophthalmic solution
• Placebo - Preservative-free artificial tears

Trial Overview The study tests if topical ketorolac eye drops can reduce inflammatory mediators in the eyes of diabetic patients and slow DR progression compared to placebo (artificial tears). Measurements of PGE2 and cytokines in the aqueous part of the eye will help assess this.

Participant Groups

Group I: Age-matched Non-diabetics Experimental Treatment 1 Intervention

We will also enroll 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole. Removed aqueous fluid that is typically discarded will instead be collected and stored at -80° C. Aqueous fluid will be tested for inflammatory markers as detailed below to provide a reference level for cross-comparison analysis.

Group II: Adult Type II Diabetics - No Diabetic Retinopathy (DR) Experimental Treatment 1 Intervention

23 Adult type II diabetic patients with no diabetic retinopathy as a control group.

Group III: Adult Type II Diabetics - Moderate NPDR - Ketorolac Experimental Treatment 2 Interventions

59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy and HbA1c ≥ 8 randomized to Ketorolac treatment.

Group IV: Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR) Experimental Treatment 1 Intervention

23 Adult type II diabetic patients with proliferative diabetic retinopathy as a control group.

Group V: Adult Type II Diabetics - Moderate NPDR - Placebo Placebo Group 2 Interventions

59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy randomized to placebo treatment.

Who Is Running the Clinical Trial?

Stephen J. Kim, MD

Lead Sponsor

Trials

1

Recruited

160+

Allergan

Industry Sponsor

Trials

782

Recruited

277,000+

Brent Saunders

Allergan

Chief Executive Officer since 2015

JD and MBA from Temple University

Dr. David Nicholson

Allergan

Chief Medical Officer since 2015

MD from Harvard Medical School

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

References

1. Germany pubmed.ncbi.nlm.nih.gov

Topical ketorolac as an adjunctive treatment with intravitreal bevacizumab in the management of diabetic macular edema: A double-masked placebo-controlled randomized clinical trial. [2021]

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

Ketorolac 0.45% ophthalmic solution. [2021]

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

Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery. [2019]

4. Mexico pubmed.ncbi.nlm.nih.gov

[Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema]. [2018]

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

Topical ketorolac in vitreoretinal surgery: a prospective, randomized, placebo-controlled, double-masked trial. [2015]

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

Intravitreal ketorolac for chronic uveitis and macular edema: a pilot study. [2015]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Canada pubmed.ncbi.nlm.nih.gov

Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Fluocinolone acetonide implantable device for diabetic retinopathy. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Medical management of diabetic retinopathy. [2016]

11. England pubmed.ncbi.nlm.nih.gov

21st Century treatment of diabetic retinopathy. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Topical treatment of diabetic retinopathy: a systematic review. [2022]