Steroids and/ or Non-steroidal Anti-inflammatory Drugs in the Postoperative Regime After Trabeculectomy. (SNAP)

Steroids and/ or Non-steroidal Anti-inflammatory Drugs in the Postoperative Regime After Trabeculectomy. An Investigator-initiated Randomized Study (The SNAP Study)

PURPOSE:

Glaucoma is the leading cause of non-curable blindness globally. Patients with glaucoma will get a gradual narrowing of the visual fields caused by compression at the optic nerve head due to increased intraocular pressure. Thus the main preventive strategy is to reduce intraocular pressure, initially by eye drops and/or laser treatment but in some patients surgery is warranted. The surgical procedure (trabeculectomy) most widely performed worldwide creates a path from the anterior chamber to the subconjunctival space and thereby lowers the IOP by producing a more efficient drainage of the aqueous humour. Surgical success depends upon controlling post-operative inflammation to ensure a functional drainage. The purpose of this blinded, randomized study is to investigate which anti-inflammatory treatment provides better long-term control of intra-ocular pressure (IOP) following glaucoma surgery (trabeculectomy) by comparing topical NSAIDs to topical steroids. Additionally, we want to explore the mechanisms behind the pathophysiology of glaucoma by evaluating retinal and optic nerve head perfusion before and after IOP lowering surgery. The primary outcome is the intraocular pressure 12 months after surgery measured by applanation tonometry.

MAIN HYPOTHESIS:

• NSAIDs and steroids are equally effective in assuring long-term filtering function and controlling IOP after trabeculectomy but may be associated with different risk profiles and bleb morphology
• Patients with lower post-operative IOP demonstrate less progression of visual field loss
• Trabeculectomy lowers IOP and provides better microcirculation in and oxygenation of inner retinal layers (i.e. ganglion cell layer) and the optic nerve head

Study Overview

• Status: Active, not recruiting
• Conditions: Glaucoma
• Intervention / Treatment: Drug: Voltaren Ophtha 1 mg/ml, GSK; Drug: Monopex 1 mg/ml, Théa

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Capital Region,
    • Glostrup, Capital Region,, Denmark, 2600
      • Department of Ophthalmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with primary open-angle glaucoma (POAG), pseudoexfoliation syndrome (PEX), pigment dispersion syndrome (PDS) or ocular hypertension
• >50 years
• Women must be postmenopausal. Women are asked if they have menstruated within the preceding 12 months
• Scheduled to undergo trabeculectomy surgery at the Department of Ophthalmology at Rigshospitalet-Glostrup, Denmark
• Informed consent to participation and ability to comply with study procedures

Exclusion Criteria:

• Known allergy to any of the contents of the pharmaceuticals (active and in-active ingredients) used in the study
• Prior intraocular surgery, except from cataract surgery. If cataract surgery has been performed, it should at least be 6 months prior to surgery
• Medical history of anterior segment dysgenesis, inflammatory/uveitic glaucoma, angle closure glaucoma, neovascular glaucoma and traumatic glaucoma
• Steroid responders
• Pregnancy
• Fertile women, i.e. women who are not menopausal and women who breastfeed
• Patients in systemic treatment with steroid or NSAID

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical, preservative-free NSAID; Topical medication are to be used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per week.	Drug: Voltaren Ophtha 1 mg/ml, GSK; Voltaren Ophtha 1 mg/ml, eye drops used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per week.
Active Comparator: Topical, preservative-free steroid; Topical medication are to be used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per week.	Drug: Monopex 1 mg/ml, Théa; Monopex 1 mg/ml, eye drops used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per week.
Experimental: Topical, preservative-free NSAID (Voltaren Ophtha 1 mg/ml, GSK; Topical medication are to be used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per wee	Drug: Voltaren Ophtha 1 mg/ml, GSK; Voltaren Ophtha 1 mg/ml, eye drops used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per week.; Drug: Monopex 1 mg/ml, Théa; Monopex 1 mg/ml, eye drops used 6 times daily for the 2 first weeks, tapering to 4 drops per day for the next 4 weeks. Depending on the clinical condition of the eye, the topical anti-inflammatory treatment will be reduced with 1 daily drop per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular pressure (IOP)	Postoperative intraocular pressure (IOP) by applanation tonometry	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best corrected visual acuity	Postoperative best corrected visual acuity in logarithm to the minimal angle of resolution (logMAR)	12 months, 24 months
Visual field	Postoperative changes in visual field by octopus autoperimetry. (MD)	12 months, 24 months
Optical nerve damage	Optical nerve damage, assessed by measuring retinal nerve fiber layer (RNFL) by peripapillary optical coherence tomography (OCT)	12 months, 24 months
Surgical success	The definition of surgical success criteria is dependent on the the severity of visual field defect (MD, mean deviation of visual sensitivity compared to those expected from the age-matched normative database) glaucoma diagnosis and achievement of target pressure without the use of medication (complete success) or with the use of glaucoma medication (qualified success); Ocular hypertension, target <25 mmHg; MD < 6 dB, target < 21 mmHg; MD 6 dB - 12 dB, target <18 mmHg; MD > 12 dB, target < 15 mmHg	12 months, 24 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Daniella Bach-Holm, MD, Ph.D., Dpt. of Ophthalmology, Rigshospitalet-Glostrup

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): June 15, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 10, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Eye Diseases; Steroid; NSAID; Anti-Inflammatory Agents, Non-Steroidal; Trabeculectomy; Anti-Inflammatory Agents
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: EudraCT nr.: 2018-001855-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No