A study to explore the best dose of mitomycin-c inside your eye during retinal detachment surgery
| ISRCTN | ISRCTN21354914 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21354914 |
| IRAS number | 1010526 |
| Secondary identifying numbers | 137155 |
- Submission date
- 12/11/2024
- Registration date
- 12/02/2025
- Last edited
- 12/02/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Eye Diseases
Plain English Summary
Background and study aims
The aim of this study is to investigate the potential benefit of a commonly used anti-inflammatory treatment to improve the outcome of surgery in eyes with retinal detachment. The retina is a thin layer which lines the inside of the eye. It is sensitive to light (like the film in a camera) and is necessary for vision. If a hole or tears develop in a retina, it can become detached. Retinal detachment is the most common eye emergency. For 1 in 5 patients the detached retina can develop scar tissue on its surface, a complication termed proliferative vitreoretinopathy (PVR). This PVR scar tissue pulls on the retina preventing the holes or tears from being repaired by standard surgery. The scar tissue increases your risk of the retina detaching again and requires more operations to resolve the problem. Multiple surgeries to remove the scar tissue often result in poor vision outcomes that do not meet the patients' expectations. Efforts to stop and treat PVR scar tissue formation have so far proved unsuccessful.
Mitomycin C (MMC) has been used in ophthalmology for over 30 years, with evidence to show its ability to stop scarring after eye surgery. This low-cost drug is currently used routinely around the globe to treat patients for other eye problems by applying MMC-soaked mini-sponges to the external surface of the eye. This study aims to demonstrate safe and potentially effective MMC treatment by direct application to the internal surface of the patient's eye with retinal detachment, at high risk of PVR. The researchers will define the most appropriate and safest dose of MMC in patients with retinal detachment.
Who can participate?
Patients aged 18 years and over who have a diagnosis of repeated retinal detachment complicated by scar tissue
What does the study involve?
Participants will receive MMC in addition to the standard eye operation
What are the possible benefits and risks of participating?
There are limited previous clinical studies using the IMP for this indication. The safety and effectiveness of intraocular use have been shown in small groups of people (about 30), with no major safety events occurring. There is a risk that in larger groups of people the safety events will be more common. In this study, the dose will start low at 0.02% MMC and potentially reach 0.05%. In previous studies, higher doses (0.04%) have been used, but not 0.05%.The IMP is commonly used in glaucoma and there have been multiple trials testing the safety of its use.
The dosing will be staggered in order to properly monitor each patient in turn. Statistical methods and DSMB judgement will be used to decide on appropriate dose escalation. The maximum dose will be 0.05%, which is only marginally more concentrated than previous studies using 0.04%.
Participants will be observed for the duration of IMP treatment, and have a visit 1 day after surgery and then weekly visits for 3 weeks.
The patients will be attending more frequently during the first 3 months following surgery, with patients attending every 2 weeks for face-to-face clinical visits/assessments until the 3-month visit.
All the study visits and care after surgery are standard practice for retinal detachment. Therefore there is no additional burden introduced by the trial visits.
Where is the study run from?
1. University College London (UK)
2. Moorfields Eye Hospital (UK)
When is the study starting and how long is it expected to run for?
November 2024 to January 2028
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
1. Jessie Barry, cctu.morph@ucl.ac.uk
2. Dr Mahiul Muqit, mahi.muqit1@nhs.net
Contact information
Public
99 High Holborn
London
WC1V 6LJ
United Kingdom
| Phone | +44 (0)20 3108 4933 |
|---|---|
| cctu.morph@ucl.ac.uk |
Scientific, Principal Investigator
162 City Road
London
EC1V 2PD
United Kingdom
| Phone | +44 (0)207 253 3411 |
|---|---|
| mahi.muqit1@nhs.net |
Study information
| Study design | Non-randomized study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A Phase I/II dose-finding study of intraocular mitomycin-c adjunct in vitrectomy for retinal detachment and proliferative vitreoretinopathy (MORPH-1) |
| Study acronym | MORPH-1 |
| Study hypothesis | Safety: To affirm the safety profile of the pharmacological doses of Mitomycin based on the occurrence of Dose Limiting Events (DLEs). Efficacy: Successful retinal re-attachment without tamponade at 6 months. 1.+10 ETDRS letters improvement in Visual acuity (ETDRS chart at 4 meters starting distance) at 6 months 2. Presence or absence of PVR grade C as measured/mapped on: 2.1. Widefield fundus photography, 2.2. OCT (Optical coherence tomography) 2.3. Clinical fundus examination 3. Mean 5-10 pc/ms reduction in flare from baseline at 6 months post-surgery |
| Ethics approval(s) |
Not yet submitted, ref: 24/NE/0211 |
| Condition | Proliferative vitreoretinopathy in rhegmatogenous retinal detachment |
| Intervention | Additional use of mitomycin-C during retinal detachment surgery (vitrectomy) including dose or dose range 0.1, 0.2, 0.3, 0.4, 0.5, and 1 mg/ml, dose frequency one dose per participant, intraocular route of administration and duration of treatment 3 minutes of application. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Mitomycin-C |
| Primary outcome measure | Safety: The occurrence of Dose Limiting Events (DLEs) over 7 days post-surgery. Safety events are assessed against DLE criteria from Day 1 to Day 7. Efficacy: Successful retinal re-attachment without tamponade at 6-month patient follow-up, as assessed by the slit-lamp examination. |
| Secondary outcome measures | 1. Change in visual acuity (measured using ETDRS chart at 4 metres starting distance) in the MMC treatment group from baseline to the 6-month final follow-up visit Target: +10 ETDRS letters improvement Acceptable: +5 ETDRS letters improvement 2. PVR grade, change from baseline to the 6-month final follow-up visit Target: Complete absence of PVR in 80% of patients in the MMC group Acceptable: Significant difference in the rate of PVR presence between the MMC group and the wider population PVR grade C as measured/mapped on widefield fundus photography, OCT and clinical fundus examination 3. Reduction in flare measured by laser flare photometry, change from baseline to the 6-month final follow-up visit Target: mean 5-10 pc/ms reduction in flare post-surgery/MMC Acceptable: mean 0-5 pc/ms reduction in flare post-surgery/MMC |
| Overall study start date | 08/11/2024 |
| Overall study end date | 30/01/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 |
| Participant inclusion criteria | 1. Individuals aged ≥18 years 2. Recurrent macula-OFF Rhegmatogenous Retinal Detachment (RRD) complicated with Proliferative vitreoretinopathy (PVR) grade C 3. Requiring surgery with silicone oil tamponade 4. Able and agree to provide written informed consent 5. Able and agree to attend all protocol mandated follow-up visits 6. If participants of childbearing potential, must have negative pregnancy test at screening visit and prior to surgery, and agree to at least one form of contraception throughout the duration of the trial |
| Participant exclusion criteria | 1. Previous known adverse reaction to mitomycin C (MMC) 2. History of open globe injury 3. A diagnosis of ocular hypertension on two or more pressure-lowering medications 4. Uncontrolled or advanced glaucoma (defined as uncontrolled eye pressure, changes to medication, recent surgery in the last 3 months or being considered for surgical treatment) 5. Uncontrolled uveitis 6. Previous steroid-induced glaucoma 7. Proliferative diabetic retinopathy or vasculopathy 8. Participant who is pregnant or is planning to become pregnant for the duration of the trial 9. Participant who has given birth within the past 6 months or is breastfeeding 10. Suspected ocular/periocular infection (e.g. Herpes Simplex Virus, Varicella Zoster Virus, mycobacterial, fungal disease) 11. Aphakia 12. Participant in whom a lensectomy is planned at the time of surgery 13. Pre-existing anterior chamber intraocular lens 14. Participant enrolled in another interventional clinical trial within 90 days prior to screening 15. Participants receiving any other treatments such as anti-cancer or autoimmune disease |
| Recruitment start date | 10/01/2025 |
| Recruitment end date | 10/06/2026 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
University/education
Comprehensive Clinical Trial Unit
99 High Holborn
London
WC1V 6LJ
England
United Kingdom
| Phone | +44 (0)2031089840 |
|---|---|
| f.ikeji@ucl.ac.uk | |
| Website | http://www.ucl.ac.uk/ |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/01/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation 4. Other publication 5. Submission to regulatory authorities |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from cctu-enquiries@ucl.ac.uk. Participant-level data will be stored securely on UCL CCTU servers. This dataset will not be made public in its raw form to protect the participant's identities and to comply with data protection. A fully anonymised dataset will be made available to researchers on submission and review of a formal request, sent in writing to UCL CCTU and the MORPH-1 Chief investigator. |
Editorial Notes
12/02/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 12/02/2025.
12/11/2024: Study's existence confirmed by the HRA.
