Vitrectomy, Subretinal Tissue Plasminogen Activator (TPA) and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative (Wet) Age-related Macular Degeneration (TIGER).
TIGER
2 other identifiers
interventional
210
5 countries
36
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Apr 2021
Longer than P75 for phase_3
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 27, 2020
CompletedFirst Posted
Study publicly available on registry
December 11, 2020
CompletedStudy Start
First participant enrolled
April 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
February 4, 2026
July 1, 2025
7.6 years
November 27, 2020
February 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
assessment of Early Treat of Diabetic Retinopathy Study (ETDRS) letters of best-corrected visual acuity (BCVA) in the study eye.
The primary outcome is the proportion of participants with a BCVA gain ≥10 ETDRS letters in the study eye at the 12 month visit.
12 months
Secondary Outcomes (7)
Assessment of Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in Best-Corrected Visual Acuity (BCVA) in the study eye
6 months
Mean ETDRS BCVA
6 and 12 months
Radner maximum reading speed
6 and 12 months
Area of scotoma size using Humphrey Field Analyser 10-2 or equivalent
6 and 12 month
National Eye Institute 25-item visual function questionnaire (NEI VFQ-25). composite score.
6 and 12 months.
- +2 more secondary outcomes
Study Arms (2)
Arm A - Surgery with aflibercept
EXPERIMENTALSurgery with aflibercept at the end of surgery, with post-operative review day 1 and week 1 (day 7)
Arm B - Aflibercept monotherapy
ACTIVE COMPARATORAflibercept monotherapy commencing at baseline.
Interventions
Intravitreal 2 mg aflibercept (Eylea, Bayer) will be injected at baseline then monthly for two further doses, then 2-monthly until month 12.
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.
Eligibility Criteria
You may qualify if:
- General
- Males or females aged at least 50 years
- Study eye
- 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).
- 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 coherence tomography (SD-OCT).
- BCVA between counting fingers and an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score of 70, inclusive.
You may not qualify if:
- General
- Serious allergy to fluorescein or indocyanine green (ICG).
- Hypersensitivity to alteplase, gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept (Eylea).
- 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.
- 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.
- 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\*.
- Unwilling, unable, or unlikely to return for scheduled follow-up for the duration of the trial.
- 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
- 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.
- SMH due to eye disease other than exudative AMD.
- Current active proliferative diabetic retinopathy.
- Current intraocular inflammation.
- Current ocular or periocular infection other than blepharitis.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- King's College Hospital NHS Trustlead
- King's College Londoncollaborator
- Fight for Sight (Funder)collaborator
Study Sites (36)
University of Bonn
Bonn, Germany
University Medical Center Hamburg Eppendorf
Hamburg, Germany
Ludwig Maximilians-University München
München, Germany
Augenzentrum am St. Franziskus-Hospital Münster
Münster, Germany
Knappschaft Kliniken Saar GmbH, Sulzbach
Sulzbach, Germany
Ulm University Hospital
Ulm, Germany
University hospital of Würzburg
Würzburg, Germany
The Institute of Eye Surgery
Waterford, Ireland
Ophthalmology Clinic Jasne Błonia
Lodz, Poland
University Hospital Bern
Bern, Switzerland
Mid and South Essex NHS Foundation Trust
Chelmsford, Essex, CM1 7ET, United Kingdom
Kent & Canterbury Hospital (East Kent University)
Canterbury, Kent, CT1 3 NG, United Kingdom
King's College Hospital NHS Foundation Trust
London, London, SE5 9RS, United Kingdom
The Princess Alexandra Eye Pavilion
Edinburgh, Scotlan, EH3 9HA, United Kingdom
Sunderland Eye Infimary
Sunderland, Tyne and Wear, SR2 9HP, United Kingdom
Hull Royal Infirmary
Hull, Yorkshire, HU3 2JZ, United Kingdom
Belfast Health and Social Care Trust
Belfast, BT9 7AB, United Kingdom
University Hospitals Sussex NHS Trust
Brighton, United Kingdom
Bristol Eye Hospital
Bristol, BS1 2LX, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Gartnavel General Hospital
Glasgow, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Royal Liverpool University Hospital
Liverpool, L7 8 XP, United Kingdom
Barts Health NHST trust - Whipps Cross University Hospital
London, E11 1NR, United Kingdom
Moorfields Eye Hospital
London, EC1V 2PD, United Kingdom
Imperial College Healthcare NHS Foundation Trust (The Western Eye Hospital)
London, NW1 5QH, United Kingdom
Maidstone and Tunbridge Wells NHS Trust
Maidstone, ME16 9QQ, United Kingdom
Manchester Royal Eye Hospital
Manchester, United Kingdom
James Cook University Hospital, (South Tees NHSFT)
Middlesbrough, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP, United Kingdom
Nottingham University Hospitals
Nottingham, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU, United Kingdom
University Hospitals Plymouth NHST
Plymouth, United Kingdom
University Hospital Southampton NHS foundation Trust
Southampton, SO16 6YD, United Kingdom
Torbay and South Devon NHS
Torquay, TQ2 7AA, United Kingdom
New Cross Hosp, Royal Wolverhampton NHST
Wolverhampton, United Kingdom
Related Publications (2)
Lee CN, Desai R, Ramazzotto L, Wafa H, Wang Y, Bunce C, Doungsong K, Ezeofor V, Edwards RT, Lois N, Steel DH, Peto T, Hillenkamp J, van Meurs JC, Reeves BC, Jackson TL. Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): update to study protocol and addition of a statistical analysis plan and health economic analysis plan for a randomised controlled surgical trial. Trials. 2025 Apr 14;26(1):131. doi: 10.1186/s13063-025-08727-8.
PMID: 40229856DERIVEDJackson TL, Bunce C, Desai R, Hillenkamp J, Lee CN, Lois N, Peto T, Reeves BC, Steel DH, Edwards RT, van Meurs JC, Wafa H, Wang Y. Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial. Trials. 2022 Jan 31;23(1):99. doi: 10.1186/s13063-021-05966-3.
PMID: 35101110DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy L Jackson, PhD, FRCOphth
Kings College London & Kings College Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 27, 2020
First Posted
December 11, 2020
Study Start
April 16, 2021
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
December 1, 2028
Last Updated
February 4, 2026
Record last verified: 2025-07