Vitrectomy, Subretinal Tissue Plasminogen Activator and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative Age-Related Macular Degeneration (TIGER): a Phase 3, Pan-European, Two-group, Observer-masked, Superiority, Randomised Controlled Surgical Trial.

IRAS Project ID: 276366

The centre of the retina (macula) at the back of the eye contains cells that give us our central vision that we use for reading and recognising faces. These cells can be damaged by a disease called wet age-related macular degeneration (AMD), where new abnormal blood vessels grow through the macula and leak fluid. This can affect vision. In some cases, wet AMD can also cause a bleed under the macula, known as a submacular haemorrhage (SMH), which can lead to marked and persistent loss of vision in the eye. The current standard treatment for wet AMD is to give injections containing 'anti-VEGF' drugs into the eye. Anti-VEGF drugs reduce the leakage of fluid so that the macula can become dry again and sight can improve. Anti-VEGFs are also the current standard of care for SMH, mainly because there is no licensed treatment for the SMH itself (patients with SMH were excluded from most wet AMD studies). The purpose of this study therefore is to compare two treatments: 1. Standard treatment for wet AMD (anti-VEGF injections). 2. Standard treatment above plus surgery. This study will find out if having surgery alongside anti-VEGF injections can improve vision further over the current standard treatment of anti-VEGF injections alone.

2021-04-16

2025-01-01

2025-12-01

Recruiting

Early phase I

210

Inclusion Criteria: General 1. Males or females aged at least 50 years Study eye 2. SMH, comprising sub-neuroretinal haemorrhage with or without sub-RPE haemorrhage, that occurs secondary to treatment naïve, or previously treated exudative AMD, including choroidal neovascularisation (CNV), idiopathic polypoidal choroidal vasculopathy (IPCV) and retinal angiomatous proliferation (RAP). 3. SMH involving the foveal centre that measures at least 1 disc diameter in greatest linear dimension. 4. Sub-neuroretinal haemorrhage at least 125 microns thick, measured at the foveal centre using spectral-domain optical coherence tomography (SD-OCT). 5. BCVA between counting fingers and an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score of 70, inclusive. Exclusion Criteria: General 1. Serious allergy to fluorescein or indocyanine green (ICG). 2. Hypersensitivity to alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept (Eylea). 3. Stroke, transient ischaemic attack or myocardial infarction within 6 months. 4. Participation in another interventional study within 12 weeks of enrolment or planned to occur during this study. 5. Women who are breast feeding, pregnant, or planning to become pregnant during the clinical trial. Any sexually active women of childbearing potential must agree continued abstinence from heterosexual intercourse or to use highly effective methods of birth control for the duration up to 12 weeks after administration of IMP or the last administration of aflibercept on the trial. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy. Females of childbearing potential are females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). Highly effective methods of birth control are those with a failure rate of \< 1% per year when employed consistently and correctly, eg. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation via oral, intravaginal, and transdermal routes; progestogen-only hormonal contraception associated with inhibition of ovulation via oral, injectable, implantable, intrauterine device (IUD), or intrauterine hormone-releasing system ( IUS); or vasectomised partner. 6. International Normalised Ratio (INR) greater than 3.5, unless it is anticipated that the INR can be brought below this level prior to vitrectomy, balancing the systemic risks with those of intraocular haemorrhage\*. 7. Unwilling, unable, or unlikely to return for scheduled follow-up for the duration of the trial. 8. Any other condition which, in the opinion of the investigator, would prevent the participant from granting informed consent or complying with the protocol, such as dementia, mental illness, or serious systemic medical disease. Study eye 9. SMH that is known or estimated to have been present for longer than 15 days, as evidenced by history, pre-trial clinical documentation, or fundus appearance. 10. SMH due to eye disease other than exudative AMD. 11. Current active proliferative diabetic retinopathy. 12. Current intraocular inflammation. 13. Current ocular or periocular infection other than blepharitis. 14. Current or known former high myopia (\>6 dioptres). 15. Aphakia. 16. Other current or pre-existing ocular conditions that, in the opinion of the Investigator, will preclude any improvement in BCVA following resolution of SMH, such as severe central macular atrophy or fibrosis, dense amblyopia, macular hole involving the fovea, or very poor BCVA prior to presentation with SMH (counting fingers or worse). 17. Inadequate pupillary dilation or significant media opacities, which will prevent adequate clinical evaluation of the posterior segment or fundus imaging. 18. Intraocular surgery within 12 weeks of enrolment except for uncomplicated cataract surgery, which is permitted within 8 weeks of enrolment. * Applies only to participants receiving warfarin.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Experimental arm: pars plana vitrectomy, sub retinal injection of recombinant tissue plasminogen activator (TPA), intravitreal sulfahexafluoride (SF6) gas tamponade and intravitreal aflibercept.\n\nActive comparator arm: intravitreal aflibercept.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 210, 'type': 'ESTIMATED'}}

2023-11-08