Laser-1st vs Drops-1st for Glaucoma and Ocular Hypertension

Study Overview
=================
Brief Summary
-----------------
This is a randomized study with two treatment arms: 'initial Selective Laser Trabeculoplasty (SLT) followed by conventional medical therapy as required' ('Laser-1st') and 'medical therapy without laser ('Medicine-1st'). It compares quality of life in the two arms at three years, while also examining the incremental cost and cost-effectiveness of Laser-1st versus Medicine-1st.

Detailed Description
-----------------
Subjects are randomly allocated to one of two treatment arms that examine treatment pathways, rather than comparing single treatments alone: 'initial Selective Laser Trabeculoplasty (SLT) followed by conventional medical therapy as required' ('Laser-1st') and 'medical therapy without laser ('Medicine-1st'). We compare quality of life in the two pathways (arms) over three years, while also examining the incremental cost and cost-effectiveness of Laser-1st versus Medicine-1st. A 'Treat in Pursuit of Control' design (TPC) compares two different routes to a pre-defined target Intraocular pressure (IOP) (pathways). It is a pragmatic study that uses published guidelines to make the complex clinical treatment choices faced in managing glaucoma, standardised between treatment arms by use of computer treatment algorithms. A UK National Institute for Health and care Excellence (NICE)-compliant evidence-based IOP Treatment Target 1 is set for each patient, according to the study treatment algorithms. They then proceed through stepped increments of treatment intensity (up to and including surgery) until a predetermined Target IOP is reached. Target IOP is reassessed in the light of objective clinical evidence of stability of glaucomatous optic neuropathy (GON) and visual function using visual field tests and automated optic nerve evaluation. Health Related Quality of Life (HRQL) and secondary outcomes are compared for patients in each pathway.

Official Title
-----------------
Health-Related Quality of Life in Two Pathways for Newly Diagnosed Open Angle Glaucoma and Ocular Hypertension: an Unmasked, Multi-centre, Randomised Controlled Trial of Initial Selective Laser Trabeculoplasty Versus Medical Therapy

Conditions
-----------------
Primary Open Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
-----------------
* Procedure: Primary Selective Laser Trabeculoplasty Treatment Pathway
* Drug: Primary Medical Treatment Pathway


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of open angle glaucoma (defined as an open drainage angle and reproducible glaucomatous visual field defects as tested by the Swedish Interactive Threshold Algorithm (SITA) algorithm on the Humphrey Visual Field or glaucomatous optic neuropathy) OR Ocular hypertension (intra-ocular pressure above 21mmHg and requiring treatment as per National Institute of Health and Care Excellence (NICE) Guidelines). Able to provide informed consent. Exclusion Criteria: Advanced glaucoma in the potentially eligible eye as determined by Early Manifest Treatment Guidelines (EMGT) criteria 77: visual field loss mean deviation worse than -12dB in the better or -15dB in the worse eye. Secondary glaucoma (e.g. pigment dispersion syndrome, rubeosis, trauma etc) or any angle closure. Any contra-indication to selective laser trabeculoplasty (e.g. unable to sit at the laser-mounted slit-lamp; past history of uveitis). Unable to use topical medical therapy due to e.g. physical infirmity and a lack of carers able to administer daily eye-drops.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 'Laser-1st'<br>Initial Selective Laser Trabeculoplasty (SLT) [PROCEDURE] followed by conventional medical therapy (eye-drops) as required. All participants in this arm start their treatment pathway with SLT. If this does not reach the predefined, patient-specific target IOP then repeat laser (once only) is given. If the IOP target is then not reached additional treatment with all standard medications may be used and ultimately surgery (trabeculectomy with mitomycin C) as needed. | Procedure: Primary Selective Laser Trabeculoplasty Treatment Pathway<br>* Primary Selective Laser Trabeculoplasty Treatment (followed by medications as required) Pathway. First treatment is SLT, 100 shots of laser over 360 degrees. If this does not reach the target IOP then repeat laser (once only) is given. If IOP not at target additional treatment with all standard medications may be used and ultimately surgery (trabeculectomy ). All available medical treatments (eye-drops) are permitted according to a pre-specified intervention protocol described in detail in the publicly available trial protocol. This begins with prostaglandin analogues, then beta-blockers followed by alpha agonists or carbonic anhydrase inhibitors. The full range of available doses, treatments and drugs is beyond this short summary.<br>* Other names: SLT; Laser First;|
| Active Comparator: Medicine-1st<br>Conventional medical therapy [DRUG] without laser. All participants in this arm start their treatment pathway medical treatment. If the IOP target is then not reached, additional treatment with all standard medications may be used and ultimately surgery (trabeculectomy with mitomycin C) as needed. During this pathway of treatment all commercially available medical treatments (eye-drops) are permitted according to a pre-specified step-wise intervention protocol described in detail in the publicly available trial protocol. This begins with prostaglandin analogues, then beta-blockers followed by alpha agonists or carbonic anhydrase inhibitors. The full range of available doses, treatments and drugs is beyond this short summary. | Drug: Primary Medical Treatment Pathway<br>* Primary Medical Treatment Pathway (multiple medications, as required). If IOP not at target additional treatment with all standard medications may be used and ultimately surgery (trabeculectomy ). All available medical treatments (eye-drops) are permitted according to a pre-specified intervention protocol described in detail in the publicly available trial protocol. This begins with prostaglandin analogues, then beta-blockers followed by alpha agonists or carbonic anhydrase inhibitors. The full range of available doses, treatments and drugs is beyond this short summary.<br>* Other names: Conventional medical therapy; Medicine First;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life using EQ-5D | Quality Adjusted Life Years by EQ-5D health states | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life using GUI | Glaucoma-specific treatment-related quality of life: Glaucoma Utility Index (GUI) | 3 years | 
| Cost-effectiveness ratio | Incremental Cost Effectiveness Ratio | 3 years | 
| Cost-effectiveness | Cost per Quality Adjusted Life Year (QALY) | 3 years | 
| Glaucoma Symptom Score (GSS) | Disease and treatment-related symptom score (patient reported outcome, PROM) | 3 years | 
| Glaucoma Quality of Life-15 (GQL-15) | Patient Reported Visual Function Score (patient reported outcome, PROM) | 3 years | 
| Glaucoma Utility Index (GUI) | Disease-Specific Utility Score (patient reported outcome, PROM) | 3 years | 
| Visual Acuity | Visual Function measured using LogMAR acuity. | 3 years | 
| Humphrey Visual Field Assessments | Visual Function measured using Mean Deviation | 3 years | 
| Heidelberg Retinal Tomographie optic nerve analysis | Optic nerve structure, measured in mean near-retinal rim width. | 3 years | 
| Goldmann Applanation Tonometry measured intra-ocular pressure | Clinical outcome of intra-ocular pressure lowering, mmHg. | 3 years | 
| Hospital visit frequency | Objective measures of treatment pathway efficacy, measured by number of hospital visits in two treatment arms over trial period. | 3 years | 
| Treatment intensity | Objective measures of treatment pathway efficacy, measured by number of medications used in two treatment arms over trial period. | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SLT, Primary Open Angle Glaucoma, Glaucoma, Ocular Hypertension, POAG, Laser