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Looking for participantsPhase3

Vitrectomy, Subretinal Tissue Plasminogen Activator (TPA) and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative (Wet) Age-related Macular Degeneration (TIGER).

Sponsor: King's College Hospital NHS Trust

NCT ID: NCT04663750

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Pars plana vitrectomy (procedure), Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12 (drug), subretinal injection of recombinant TPA (Alteplase) up to a maximum of 25 micrograms in 0.2 mls (drug), Intravitreal 20% sulfahexafluoride (SF6) gas tamponade (drug)
How long the study runs
Study runs about 92 months (dates as stated)
About the drug or intervention
Pars plana vitrectomy — procedure: Pars plana vitrectomy · Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12 — drug: Intravitreal 2 mg aflibercept will be injected at baseline then monthly for two further doses, then 2-monthly until month 12. · subretinal injection of recombinant TPA (Alteplase) up to a maximum of 25 micrograms in 0.2 mls — drug: Subretinal injection of recombinant TPA (Alteplase, Actilyse, Boehringer Ingelheim) up to a maximum of 25 micrograms in 0.2 mls. · Intravitreal 20% sulfahexafluoride (SF6) gas tamponade — drug: Intravitreal 20% sulfahexafluoride (SF6) gas tamponade.
Patient visit burden
Not specified by the sponsor

In plain English

This trial, called TIGER, looks at a possible treatment for bleeding under the central part of the retina (the macula) caused by wet age-related macular degeneration. The treatment being studied involves eye surgery (vitrectomy), an injected medicine called tissue plasminogen activator (TPA) that helps break down the blood, and a gas bubble placed in the eye. It is sponsored by King's College Hospital NHS Trust.

Who can take part

  • Adults aged 50 or over, male or female.
  • Bleeding under the macula caused by wet age-related macular degeneration, including some related eye conditions (choroidal neovascularisation, idiopathic polypoidal choroidal vasculopathy, and retinal angiomatous proliferation).
  • The bleed covers the centre of the macula and is at least the size of one optic disc across.
  • The bleed under the retina is at least 125 microns thick at its centre, measured with a detailed eye scan.
  • Vision in the study eye is between counting fingers and a score of 70 letters on a standard vision chart.

Who may not be able to

  • A serious allergy to fluorescein or indocyanine green (a dye used in eye tests).
  • An allergy to certain medicines used in the trial (alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept).
  • A stroke, mini-stroke or heart attack in the last 6 months.
  • Taking part in another treatment study in the last 12 weeks, or planning to during this trial.
  • Being pregnant, breastfeeding, or planning a pregnancy during the trial. People who can have children and their partners must use highly effective contraception for a period during and after the trial.
  • A blood clotting measure (INR) above 3.5, unless it can safely be lowered before surgery.
  • Being unable or unlikely to attend follow-up visits for the whole trial.
  • Any other condition that would make it hard to give informed consent or follow the trial, such as dementia or serious illness.
  • The bleed having been present for more than about 15 days.
  • The bleed being caused by something other than wet age-related macular degeneration.
  • Active severe diabetic eye disease, inflammation in the eye, or an eye or eyelid infection (other than mild eyelid inflammation).
  • Being very short-sighted (more than 6 dioptres), past or present.
  • Having no natural lens in the eye (aphakia).
  • Other eye problems that would stop vision improving even if the bleed cleared, such as severe scarring or thinning of the macula, a lazy eye, or a macular hole.
  • Pupils that will not widen enough, or cloudy areas in the eye, that would stop clear eye examinations or photographs.
  • Eye surgery in the last 12 weeks (simple cataract surgery is allowed if it was at least 8 weeks ago).

What taking part involves

  • • Vitrectomy: surgery to remove the clear gel from inside the eye.
  • • Injection of a medicine called tissue plasminogen activator (TPA) under the retina to help break down the blood.
  • • A gas bubble placed inside the eye.
  • • Aflibercept may also be given as part of the trial (it is listed among the trial medicines).

Time commitment: Not stated — ask the trial team.

Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.

Type of study
Testing a treatment
Ages
50 Years to 120 Years
Who
All
Number of participants
210
Started
2021-04-16
Last checked
2026-07

Plain English Summary

What is this study?

  • • Testing a new treatment for eye diseases
  • • Phase3 - 210 participants
  • • 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

Who can take part?

  • • Ages 50 Years to 120 Years
  • • Diagnosed with eye diseases

Where?

  • • Chelmsford - Mid and South Essex NHS Foundation Trust
  • • Canterbury - Kent & Canterbury Hospital (East Kent University)
  • • London - King's College Hospital NHS Foundation Trust
  • • Edinburgh - The Princess Alexandra Eye Pavilion
  • • +22 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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.

More detail

SMH is a rare but devastating complication of wet AMD. Untreated, SMH typically leads to permanent and severe loss of vision, ranging from 6/30 (approximately 20% normal vision) to only being able to perceive light versus dark (no useful vision). There are no large, published, randomised controlled trials (RCTs) evaluating treatments for SMH. Hence there is no widely-accepted treatment approach. Some patients are managed by observation, others with drugs (anti-VEGF) injected into the eye, others with eye surgery (vitrectomy, subretinal TPA, gas) and combinations thereof. From a regulatory perspective the standard treatment is with anti-VEGF injections alone, since these are licensed for the treatment of wet AMD (and there is no treatment licensed for SMH). This study will test the hypothesis that surgery with anti-VEGF injections for SMH due to wet AMD is superior to the current standard of treatment with anti-VEGF injections alone. The results will help guide future clinical practice to maximise the visual outcomes for patients with SMH. Most potential participants will present or be referred to the clinics of the investigators who provide routine care for wet AMD. Referrals may arise from research networks, family physicians, optometrists or ophthalmologists. After confirming the diagnosis of SMH, informed consent will be obtained and potential participants will be asked to sign a consent form. Following this, baseline screening will occur, including a clinical examination and a series of vision tests to confirm eligibility to take part in the study. Once successfully screened, each participant will be randomly allocated to one of the two study groups: 1. Standard current treatment with anti-VEGF injections: participants will be given their first injection into the study eye at the screening/baseline visit, or otherwise within a few days. Following this, each participant will receive another injection at month 1, another at month 2 and thereafter one injection every two months until the end of the study (month 12). Anaesthetic eye drops will be given to numb the eye before each injection. 2. Standard current treatment with anti-VEGF injections plus surgery: participants will be given their first injection into the study eye at the time of surgery and then all other injections as per the schedule above. During the surgery, the clear gel (vitreous) that fills the inside of the eye will be removed and a clot-busting drug (TPA) will be injected into the eye to help break up the blood clot. The inside of the eye will then be filled with gas to help push the dissolved clot away from the macula. Various options for anaesthetic will be discussed with each participant before surgery, including (i) local anaesthetic only, (ii) local anaesthetic with some sedation, to reduce any anxiety or (iii) general anaesthetic so the participant is asleep during the surgery. If the participant also has a cataract or is likely to develop one, the surgeon will discuss the option of having cataract surgery as part of the same operation. After the surgery, participants will be asked to keep their heads forward, to enable the gas bubble to move the blood clot away from the macula. This should be done for 50 minutes out of every hour for the first five days. During the 10-minute breaks, participants will be encouraged to move around and be active. At night, participants will be asked to sleep on the side of the operated eye, i.e. with the operated eye lowest. The gas is expected to disappear from the eye around 4-8 weeks after surgery. Participants who have had surgery will be instructed to return for follow up the day after surgery and also one week later. All participants will also have a clinical examination at 6 and 12 months that will include tests of their vision. They will also attend regularly for anti-VEGF injections: every month for the first three visits, then every two months until the study is completed at month 12.

Eye DiseasesMacular Degeneration, WetSub-Macular Hemorrhage

How this trial compares with your answers

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What we know so far

Condition· Matched your search
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Still need:

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 50 Years - 120 Years
  • Who can join: All genders

What the study is looking for

  • ✓General
  • ✓Males or females aged at least 50 years
  • ✓Study eye
  • ✓SMH involving the foveal centre that measures at least 1 disc diameter in greatest linear dimension.
  • ✓Sub-neuroretinal haemorrhage at least 125 microns thick, measured at the foveal centre using spectral-domain optical...

Who cannot take part

  • ✗General
  • ✗Serious allergy to fluorescein or indocyanine green (ICG).
  • ✗Hypersensitivity to alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept.
  • ✗Stroke, transient ischaemic attack or myocardial infarction within 6 months.
  • ✗Participation in another interventional study within 12 weeks of enrolment or planned to occur during this study.
See the full criteria
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. 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.

Where Is This Study? (26 UK sites)

Mid and South Essex NHS Foundation Trust

Chelmsford CM1 7ET, United Kingdom

Recruiting
Site contact (verified)
Raiji KoothoorPrincipal Investigator

Kent & Canterbury Hospital (East Kent University)

Canterbury CT1 3 NG, United Kingdom

Recruiting
Site contact (verified)
Yvonne LuoPrincipal Investigator

King's College Hospital NHS Foundation Trust

London SE5 9RS, United Kingdom

Recruiting
Site contact (verified)
Timothy L Jackson, PhD, FRCOphthPrincipal Investigator
Timothy L Jackson, PhD, FRCOphth+44 20 3299 1297
Riti Desai, M.Sc, M.Phil+44 20 3299 1297ritidesai@nhs.net

The Princess Alexandra Eye Pavilion

Edinburgh EH3 9HA, United Kingdom

Recruiting
Site contact (verified)
Manjit MehatPrincipal Investigator

Sunderland Eye Infimary

Sunderland SR2 9HP, United Kingdom

Recruiting
Site contact (verified)
Jonathan SmithPrincipal Investigator

Hull Royal Infirmary

Hull HU3 2JZ, United Kingdom

Recruiting
Site contact (verified)
Abdallah EllabbanPrincipal Investigator

Belfast Health and Social Care Trust

Belfast BT9 7AB, United Kingdom

Recruiting
Site contact (verified)
Noemi LoisPrincipal Investigator

University Hospitals Sussex NHS Trust

Brighton, United Kingdom

WITHDRAWN
Hospital R&D contact (matched)

Scott Harfield

uhsussex.research@nhs.net01273 696955 ext. 67497

Bristol Eye Hospital

Bristol BS1 2LX, United Kingdom

Recruiting
Site contact (verified)
Johannes KellerPrincipal Investigator

Royal Devon and Exeter Hospital

Exeter, United Kingdom

Recruiting
Site contact (verified)
Conor RamsdenPrincipal Investigator

Gartnavel General Hospital

Glasgow, United Kingdom

WITHDRAWN

Leicester Royal Infirmary

Leicester, United Kingdom

Recruiting
Site contact (verified)
Somnath BanerjeePrincipal Investigator

Royal Liverpool University Hospital

Liverpool L7 8 XP, United Kingdom

Recruiting
Site contact (verified)
Ruman HussainPrincipal Investigator

Barts Health NHST trust - Whipps Cross University Hospital

London E11 1NR, United Kingdom

Recruiting
Site contact (verified)
Hadi ZambarakjiPrincipal Investigator

Moorfields Eye Hospital

London EC1V 2PD, United Kingdom

Recruiting
Site contact (verified)
Louisa WickhamPrincipal Investigator

Imperial College Healthcare NHS Foundation Trust (The Western Eye Hospital)

London NW1 5QH, United Kingdom

Recruiting
Site contact (verified)
Rahila ZakirPrincipal Investigator

Maidstone and Tunbridge Wells NHS Trust

Maidstone ME16 9QQ, United Kingdom

Recruiting
Site contact (verified)
Luke MembreyPrincipal Investigator

Manchester Royal Eye Hospital

Manchester, United Kingdom

Recruiting
Site contact (verified)
Tsveta IvanovaPrincipal Investigator

James Cook University Hospital, (South Tees NHSFT)

Middlesbrough, United Kingdom

Recruiting
Site contact (verified)
Saad AhmedPrincipal Investigator

Royal Victoria Infirmary

Newcastle upon Tyne NE1 4LP, United Kingdom

Recruiting
Site contact (verified)
Roxane HillierPrincipal Investigator

Nottingham University Hospitals

Nottingham, United Kingdom

Recruiting
Site contact (verified)
Alexander FossPrincipal Investigator

Oxford University Hospitals NHS Foundation Trust

Oxford OX3 9DU, United Kingdom

Recruiting
Site contact (verified)
Sher AslamPrincipal Investigator

University Hospitals Plymouth NHST

Plymouth, United Kingdom

Recruiting
Site contact (verified)
Vasant RamanPrincipal Investigator

University Hospital Southampton NHS foundation Trust

Southampton SO16 6YD, United Kingdom

Recruiting
Site contact (verified)
Bhaskar GuptaPrincipal Investigator

Torbay and South Devon NHS

Torquay TQ2 7AA, United Kingdom

Recruiting
Site contact (verified)
Eddie DoylePrincipal Investigator

New Cross Hosp, Royal Wolverhampton NHST

Wolverhampton, United Kingdom

Recruiting
Site contact (verified)
Kam BalagganPrincipal Investigator

How to Get in Touch

Riti Desai, M.Sc.,M.Phil.

Sponsor contact

CONTACT

0044 2032991297 ritidesai@nhs.net

Lisa Ramazzotto, M.Pharm

Sponsor contact

CONTACT

0044 2032991297 kch-tr.tigerstudy@nhs.net
Data sourced from ClinicalTrials.gov · Last verified: 2026-07