Condition category
Eye Diseases
Date applied
02/05/2017
Date assigned
19/05/2017
Last edited
08/11/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Diabetic retinopathy is the damage of the retina (the light-sensitive tissue lining the back of the eye) caused by diabetes. People with diabetic retinopathy may lose vision as a result of them developing what is called diabetic macular oedema (DMO). DMO is the most common complication of diabetes in the back of the eye. In DMO, fluid leaks in the centre of the retina (macula). The accumulation of this fluid reduces the vision, as the retina needs to be dry to work properly. If the fluid is left untreated, permanent and irreversible visual loss will occur. The amount of fluid in the macula can be measured by doing a scan of the eye called optical coherence tomography (OCT). Depending on the amount of fluid present in the macula, people with DMO will be offered medicines known as anti-vascular endothelial growth factor (anti-VEGF) or laser treatment. The National Institute of Health and Care Excellence (NICE) found that laser treatment was effective in people with DMO and retinas that had been thickened by fluid but below to a certain limit (when the centre of the retina is less than 400 microns in thickness as measured by the OCT) and offers good value for money compared to anti-VEGF injections. Both, standard laser and micropulse laser, are being used currently in ophthalmic clinics across the world. The aim of this study is to compare the effectiveness of these two lasers in the treatment of patients with DMO.

Who can participate?
Adults who have diabetic retinopathy and DMO.

What does the study involve?
At the start of the study, all participants have an eye examination and have a sample of blood taken to check their blood sugar control. In addition, their medical history is taken and participants fill in some questionnaires about how they perceive their sight and how their sight may affect their life. Participants are then randomly allocated to one of two groups. Those in the first group are treated with the micropulse laser and those in the second group are treated with the standard laser. The participants do not know which laser they are being treated with. Participants in both groups attend clinic appointments after four, eight, 12, 16, 20 and 24 weeks so that the effects of the treatment can be assessed.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved with participating.

Where is the study run from?
Royal Victoria Hospital, Belfast and 10 other NHS hospitals (UK)

When is the study starting and how long is it expected to run for?
November 2014 to April 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Catherine Adams
CatherineX.Adams@nictu.hscni.net

Trial website

Contact information

Type

Public

Primary contact

Dr Catherine Adams

ORCID ID

Contact details

Northern Ireland Clinical Trials Unit
1st Floor Elliott Dynes Building
The Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 28 90635794
CatherineX.Adams@nictu.hscni.net

Additional identifiers

EudraCT number

2016-003804-29

ClinicalTrials.gov number

Protocol/serial number

33318

Study information

Scientific title

Diabetic Macular Oedema and Diode Subthreshold Micropulse Laser (DIAMONDS): A pragmatic, multicentre, allocation concealed, prospective, randomised, non-inferiority double-masked trial

Acronym

DIAMONDS

Study hypothesis

The aim of this study is to evaluate the clinical effectiveness and cost-effectiveness of Diode Subthreshold Micropulse Laser (DSML), when compared with standard threshold laser, for the treatment of patients with Diabetic Macular Oedema (DMO) with a central retinal subfield thickness of (CST) of < 400 microns.

Ethics approval

Office for Research Ethics Committees Northern Ireland- HSC REC A, 17/08/2016, ref: 16/NI/0145

Study design

Randomised; Interventional; Design type: Treatment, Other

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Ophthalmology, Primary sub-specialty: Glaucoma; UKCRC code/ Disease: Eye/ Disorders of choroid and retina

Intervention

Participants are randomised to one of two groups in a 1:1 ratio by an automated randomisation system to generate the random allocation sequence.

Intervention group: Participants undergo treatment with the micropulse laser. This involves the use of a laser technology aimed at minimising damage (“tissue-sparing”) to choroid and retina but maintaining treatment efficacy by its selective effect on the retinal pigment epithelium (RPE). It is performed using a laser that, instead of delivering a continuous-wave laser beam, as the standard laser, it provides very small, repetitive, low energy pulses of laser separated by a brief rest period. This rest period allows the tissue to cool down between laser pulses avoiding the increased tissue heat that would be produced by continuous laser and allowing the use of lower laser energy power to achieve an effect. The reduced heat produced in the tissue and the reduced energy power required for the treatment may reduce side effects. Specifically, the technology does not appear to cause retinal burns or scars associated with decreased retinal sensitivity in treated areas.

Control group: Participants receive standard treatment. This involves the use of standard threshold laser with any of the devices used currently for this purpose (e.g. frequency-doubled neodymium-doped yttrium aluminium garnet (Nd:YAG) 532 nm laser, argon laser, diode [561nm or IQ (577nm)] laser. Standard laser is applied to areas of thickened retina, macular non-perfusion and leaking microaneurysms, in accordance the modified ETDRS technique.

At baseline and again after 4, 8, 12, 16, 20, 24 months, participants undergo an opthamological examination and OCT scan to establish their eligibility for the study and to determine the changes to their eye following laser treatment. Health and vision related quality of life will be evaluated through the use of the EQ-5D -5L, the NEI VFQ-25 and the VisQoL which will be obtained t baseline and months 12 and 24.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

BCdVA in the study eye is assessed by a BCdVA test (using ETDRS visual acuity charts at 4 meters) at baseline and months 4,8,12,16,20 and 24.

Secondary outcome measures

1. Binocular BCdVA is assessed by a binocular BCdVA test (using ETDRS visual acuity charts at 4 meters) at baseline and 24 months
2. Central subfield retinal thickness, as determined by spectral domain OCT at baseline and 24 months
3. Mean deviation (MD) of the Humphrey 10-2 visual field is assessed by a Humphrey 10-2 visual field test at baseline, 12 and 24 months
4. Percentage (%) of people meeting driving standards is assessed by an Esterman binocular visual field test at baseline and 24 months
5. Visual functioning (NEI VFQ-25), general health (EQ-5D-5L) and vision and quality of life (VisQol) are measured using NEI VFQ25, EQ-5D 5L and VisQoL questionnaire scores at baseline and 24 months
6. Incremental cost per quality-adjusted life year (QALY) gained is assessed by a Markov model based cost-utility analysis which will extend beyond the trial analysis period to estimate the longer-term cost-effectiveness, with costs and benefits discounted at 3.5%. The model will be populated by data from the trial and supplemented by estimates of effectiveness, quality of life and costs from published literature and expert opinion.
7. Side effects are measured by a review of the participant’s medical and ophthalmic history at 4, 8, 12, 16, 20, 24 months
8. Number of laser treatments needed is assessed by the treating ophthalmologist at 4, 8, 12, 16, 20, 24 months
9. Use of additional treatments (other than laser) is assessed by the treating ophthalmologist at 4, 8, 12, 16, 20, 24 months

Overall trial start date

01/11/2014

Overall trial end date

30/04/2019

Reason abandoned

Eligibility

Participant inclusion criteria

Patients with diabetic retinopathy and centre involving DMO, as determined by using spectral domain optical coherence tomography (SD-OCT), in one or both eyes with:
1. Central retinal subfield thickness of > 300 but < 400 microns as determined by SD-OCT due to diabetic macular oedema
OR
2. Central retinal subfield thickness of < 300 microns provided that intraretinal and/or subretinal fluid is present in the central subfield (central 1 mm) related to diabetic macular oedema
AND
3. Visual acuity of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent > 20/320)
4. Amenable to laser treatment, as judged by the treating ophthalmologist
5. Over 18 years of age

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 266; UK Sample Size: 266

Participant exclusion criteria

Eyes of patients will not be included in the study if::
1. The macular oedema is due to causes other than diabetic macular oedema such as epiretinal membrane, vitreomacular traction, vein occlusion, or others
2. The eye is ineligible for macular laser treatment, as judged by the treating ophthalmologist
3. The eye has DMO and central subfield retinal thickness (CST) of > 400 microns.
4. The eye has active proliferative diabetic retinopathy (PDR) requiring treatment.
5. The eye has received intravitreal Anti- Vascular Endothelical Growth Factor (Anti-VEGF) therapy within the previous two months.
6. The eye has received macular laser treatment within the previous 12 months.
7. The eye has received intravitreal injection of steroids.
8. The eye has received cataract surgery within the previous six weeks
9. The eye has received panretinal photocoagulation within the previous 3 months

The patient:
1. Is on pioglitazone and the drug cannot be stopped 3 months prior to entering into the trial and for the duration of the study
2. Has chronic renal failure requiring dialysis or kidney transplant
3. Has any other condition that in the opinion of the investigator would preclude participation in the study (such as unstable medical status or severe disease that would make it difficult for the patient to be able to complete the study)
4. Has very poor glycemic control and started intensive therapy within the previous 3 months
5. Will use an investigational drug during the study

Recruitment start date

18/01/2017

Recruitment end date

01/04/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Hospital, Belfast
Belfast Health & Social Care Trust Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Trial participating centre

Moorfields Eye Hospital
162 City Road
London
EC1V 2PD
United Kingdom

Trial participating centre

The John Radcliffe Hospital
Oxford Eye Hospital Headley Way
Oxford
EC1V 2PD
United Kingdom

Trial participating centre

Manchester Royal Eye Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Sunderland Eye Infirmary
Queen Alexandra Road
Sunderland
SR2 9HP
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Bristol Eye Hospital
Lower Maudlin Street
Bristol
BS1 2LX
United Kingdom

Trial participating centre

Frimley Park Hospital
Portsmouth Road
Frimley
GU16 7UJ
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Directorate of Opthalmology Glossford Road
Sheffield
S10 23F
United Kingdom

Trial participating centre

King's College Hospital
Normandy Building Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Hinchingbrooke Hospital
Hinchingbrooke Park Hinchingbrooke
Huntingdon
PE29 6NT
United Kingdom

Sponsor information

Organisation

Belfast Health & Social Care Trust

Sponsor details

Research & Governance Office
2nd Floor
KEB
Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 2890 636 366
alison.murphy@belfasttrust.hscni.net

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The final study report will be provided by the Trial Statistician. It is anticipated that the study findings will be published in national and international peer review journals and these articles will be led by the CI. This will secure a searchable compendium of these publications and make the results readily accessible to the public and health care professionals. In addition, study findings may be presented at both national and international meetings and to appropriate patient groups.
A report containing the methodology and results of this randomised trial will be published as a Health Technology Assessment monograph, freely accessible via the NIHR HTA webpage. The Royal College of Ophthalmologist will be contacted once the study is completed to allow the trial‟s findings to be incorporated in future Diabetic Retinopathy guidelines.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository the MACRO Database (https://nictu.hscni.net/Macro/)

Intention to publish date

30/04/2020

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

08/11/2017: The ISRCTN prospective/retrospective flag compares the date of registration with the recruitment start date and does not include any grace period. The registration of this study was requested through the NIHR Portfolio and was finalised within 6 months of the recruitment starting.