Exudative Macular DegenerationPhase 2/3TAPASNCT01835067
Intravitreal tPA and C3F8 for the Treatment of Submacular Haemorrhage as a Complication of Neovascular AMD
A Phase 2/3 study testing Ranibizumab, C3F8 Gas and tPA in people with Exudative Macular Degeneration and Retinal Hemorrhage, run by King's College Hospital NHS Trust at 5 sites in United Kingdom.
Trial summary
This study will recruit patients who have recently had a submacular haemorrhage (bleed under the part of the retina responsible for detailed vision), as a complication of wet age-related macular degeneration (wet AMD). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Exudative Macular Degeneration, Retinal Hemorrhage
- What is being tested?
- Ranibizumab, C3F8 Gas and tPA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Sep 2014to Dec 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults of either sex aged 50 years and older;
- SMH associated with treatment-naive or previously treated wet AMD, including retinal angiomatous proliferation (RAP) and idiopathic polypoidal choroidal vasculopathy (IPCV);
- SMH of at least 1 disc area, involving the fovea, and of sufficient density to obscure RPE detail;
- Written informed consent to participate in the study.Only one eye will be eligible for inclusion in this study.
Who cannot join
- SMH that is known to have been present for greater than 2 weeks duration, as evidenced by history, pre-trial documentation, or fundus appearance;
- Presence of significant vitreous haemorrhage precluding accurate retinal assessment in the study eye;
- Diabetic maculopathy in the study eye;
- Visually significant cataract in the study eye;
- Amblyopia in the study eye;
- Presence of other ocular disease causing concurrent vision loss in the study eye;
Show all 15Show fewer
- Advanced glaucoma in the study eye (cup-to-disc ratio greater than 0.8);
- Pregnant and or lactating women;
- Women of childbearing potential including those who are not sterilised or at least one year post menopausal;
- Participation in a clinical interventional trial in the preceding 6 months;
- Documented evidence of a visual acuity less than 25 ETDRS letters at three consecutive visits in the study eye, prior to the onset of submacular haemorrhage;
- Participants who are known to have been ineligible for NICE approved ranibizumab therapy prior to the development of the SMH;
- Current treatment for wet age-related macular degeneration with an intravitreal agent other than ranibizumab, bevacizumab or aflibercept;
- Patients who, in the opinion of the Investigator, would not be willing or able to comply with the study protocol, including posturing requirements.
- Patients who show insufficient understanding of the clinical trial or treatment options.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
Hull & East Yorkshire Hospital NHS Trust
Hull, HU3 2JZ
King's College Hospital NHS Foundation Trust
London, SE5 9RS
Maidstone Hospital
Maidstone, Kent, ME16 9QQ
Southend University Hospital NHS Foundation Trust
Southend, SS0 0RY
Sunderland Eye Infimary
Sunderland, Tyne and Wear, SR2 9HP
About this study
Official title: Intravitreal Tissue Plasminogen Activator And Perfluoropropane for Neovascular Age-related Macular Degeneration With Associated Submacular Haemorrhage: a Multi-centre, Randomized, Double-masked, Sham-controlled, Factorial, Feasibility Study
This study will recruit patients who have recently had a submacular haemorrhage (bleed under the part of the retina responsible for detailed vision), as a complication of wet age-related macular degeneration (wet AMD). Wet AMD is a very common disease where abnormal blood vessels form under the retina and leak, causing a significant reduction in vision.
The study will investigate treatment of the bleed with various combinations of the two drugs: tissue plasminogen activator (tPA) - designed to dissolve the blood clot; and perfluoropropane (C3F8) - designed to shift the blood clot away from the central part of the retina (the macula). tPA is a commonly used 'clot-buster' drug for the treatment of stroke. C3F8 is a gas commonly used in eye surgery. Patients recruited will be divided into four groups: control group that receive none of the above drugs; one group that receives only tPA; one group that receives only C3F8; and one group that receives both.
Read more
All patients will receive the current gold standard treatment for wet AMD, ranibizumab (Lucentis®).
The aim of the study is to improve vision in a condition, which left untreated, would cause severe visual loss.
Read the detailed description
Age-related macular degeneration (AMD) is the commonest cause of blindness worldwide. Its prevalence increases with age, being relatively rare under 60 years and reaching its peak incidence in those older than 80 years. AMD principally affects central vision, which is responsible for the ability to see fine detail and the disease rapidly destroys the ability to read normal print, recognise faces, drive, and watch television. It can therefore have a profound effect on quality of life.
There are two main forms of AMD; the dry form, in which there is slow degeneration of the cells responsible for sight, resulting in gradual visual loss; and the wet form (neovascular), which occurs when abnormal blood vessels (choroidal neovascularisation) grow under the retina, the part of the eye which is responsible for sensing light, like the film of a camera. These new blood vessels have weak walls leading to leakage of fluid (oedema), and sometimes significant amounts of bleeding (submacular haemorrhage - SMH). These rapidly lead to central visual distortion and blurring. Although the dry form is commoner, the wet form more commonly results in profound central visual loss and is responsible for the majority of cases that ultimately require blind registration.
The current best treatment ('gold-standard') for wet AMD is the drug ranibizumab (Lucentis®), which aims to shrink and destroy the abnormal blood vessels responsible for the visual symptoms. In several trials ranibizumab has been shown to improve vision in patients with wet AMD.
It is not uncommon for patients with wet AMD to develop SMH, which when it occurs, significantly reduces the patient's visual prognosis. SMH is thought to have a number of toxic consequences on the retinal function.
This study investigates the use of two drugs: tissue plasminogen activator (tPA), a 'clot-buster' drug used to treat stroke, which is designed to dissolve the clot over the central retina (macula); and perfluoropropane (C3F8), a gas commonly used in retinal surgery, which is designed to displace the clot away from the macula.
This study is a randomized, double-masked, clinical trial with a recruitment target of 55 people with SMH and wet AMD. Participants will be allocated to one of four groups; a control group receiving none of the above drugs; one group receiving only tPA; one group receiving only C3F8; and one group receiving both. All patients will receive the 'gold-standard' treatment of ranibizumab for their underlying wet AMD. We aim to determine if tPA and/or C3F8 produce a visual outcome that is superior to standard care, with a favourable safety profile. We will also measure the size of the blood clot and scarring using computer analysis of macula photographs.
- Conditions
- Exudative Macular Degeneration, Retinal Hemorrhage
- Being tested
- Ranibizumab, C3F8 Gas, tPA
- Keywords
- Macular degeneration, Submacular haemorrhage
- Medical subject headings
- Wet Macular Degeneration, Retinal Hemorrhage, Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
Also called Lucentis®
Single intravitreal injection of 500 micrograms ranibizumab in 0.05mls
C3F8 GasDrug
Also called Perfluoropropane, Perflutren, Octafluoropropane
Single intravitreal injection of 0.3 mls C3F8
tPADrug
Also called tissue plasminogen activator, alteplase, Actilyse®
Single intravitreal injection of 50 micrograms tPA in 0.05 mls
| Study group | Role | What they receive |
|---|---|---|
| Control Group (A) | Sham comparator | Ranibizumab only (active control). Participants will receive a 'sham injection' to simulate C3F8 and/or tPA administration. Receives: Drug: Ranibizumab |
| C3F8 Only Group (B) | Experimental | C3F8 given. Ranibizumab given as standard. Receives: Drug: Ranibizumab; Drug: C3F8 Gas |
| tPA and C3F8 Group (C) | Experimental | Both C3F8 gas and tPA given. Ranibizumab given as standard. Receives: Drug: Ranibizumab; Drug: C3F8 Gas; Drug: tPA |
| tPA Only Group (D) | Experimental | tPA given. Ranibizumab given as standard. Receives: Drug: Ranibizumab; Drug: tPA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean ETDRS visual acuity
Measured: 3 months
Secondary outcomes (7)
Mean ETDRS visual acuity
Measured: 1 and 12 months
Percentage patients 15 letters or greater improvement in ETDRS visual acuity
Measured: 12 months
Percentage patients 0 letters or greater improvement in ETDRS visual acuity
Measured: 12 months
Percentage patients 15 letters or greater loss in ETDRS visual acuity
Measured: 12 months
Mean total area of macular haemorrhage on colour fundus photography
Measured: 1, 3 and 6 months
Greatest linear dimension of macular haemorrhage on colour fundus photography
Measured: 1, 3 and 6 months
Presence of subfoveal blood on colour fundus photography
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2013 (estimated)
- Study startSep 2014
- Primary completionNov 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Exudative Macular DegenerationStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy L Jackson, PhD,FRCOpht, Principal investigator, King's College Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01835067
- Sponsor's protocol ID
- EudraCT Number: 2012-004078-24
- Acronym
- TAPAS
- Status last verified
- Feb 2020
- First submitted
- 16 Apr 2013
- Last updated
- 14 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: The Investigator(s) and the institution(s) shall permit trial-related monitoring, audits, REC review, and regulatory inspections (where appropriate) by providing the Sponsors, Regulators and REC direct access to source data and other documents (i.e. patients' case sheets, blood test reports, X-ray reports, histology reports etc). Where necessary, inspection may also take place at the site's facilities.
Publications
Murphy GSP, Saleh A, Ayis S, Cheema MR, Mehta A, Steel DH, Membrey L, Costen M, Jackson TL. Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration: A Factorial Randomized Clinical Trial. JAMA Ophthalmol. 2024 Dec 1;142(12):1157-1164. doi: 10.1001/jamaophthalmol.2024.4297.
PubMed 39418015
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravitreal Tissue Plasminogen Activator And Perfluoropropane for Neovascular Age-related Macular Degeneration With Associated Submacular Haemorrhage: a Multi-centre, Randomized, Double-masked, Sham-controlled, Factorial, Feasibility Study
- ClinicalTrials.gov ID
- NCT01835067
- Acronym / sponsor ID
- TAPAS / EudraCT Number: 2012-004078-24
- Conditions
- Exudative Macular Degeneration, Retinal Hemorrhage
- Keywords
- Macular degeneration, Submacular haemorrhage
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Nov 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 18 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will recruit patients who have recently had a submacular haemorrhage (bleed under the part of the retina responsible for detailed vision), as a complication of wet age-related macular degeneration (wet AMD). Wet AMD is a very common disease where abnormal blood vessels form under the retina and leak, causing a significant reduction in vision.
The study will investigate treatment of the bleed with various combinations of the two drugs: tissue plasminogen activator (tPA) - designed to dissolve the blood clot; and perfluoropropane (C3F8) - designed to shift the blood clot away from the central part of the retina (the macula). tPA is a commonly used 'clot-buster' drug for the treatment of stroke. C3F8 is a gas commonly used in eye surgery. Patients recruited will be divided into four groups: control group that receive none of the above drugs; one group that receives only tPA; one group that receives only C3F8; and one group that receives both.
All patients will receive the current gold standard treatment for wet AMD, ranibizumab (Lucentis®).
The aim of the study is to improve vision in a condition, which left untreated, would cause severe visual loss.
Detailed description
Age-related macular degeneration (AMD) is the commonest cause of blindness worldwide. Its prevalence increases with age, being relatively rare under 60 years and reaching its peak incidence in those older than 80 years. AMD principally affects central vision, which is responsible for the ability to see fine detail and the disease rapidly destroys the ability to read normal print, recognise faces, drive, and watch television. It can therefore have a profound effect on quality of life.
There are two main forms of AMD; the dry form, in which there is slow degeneration of the cells responsible for sight, resulting in gradual visual loss; and the wet form (neovascular), which occurs when abnormal blood vessels (choroidal neovascularisation) grow under the retina, the part of the eye which is responsible for sensing light, like the film of a camera. These new blood vessels have weak walls leading to leakage of fluid (oedema), and sometimes significant amounts of bleeding (submacular haemorrhage - SMH). These rapidly lead to central visual distortion and blurring. Although the dry form is commoner, the wet form more commonly results in profound central visual loss and is responsible for the majority of cases that ultimately require blind registration.
The current best treatment ('gold-standard') for wet AMD is the drug ranibizumab (Lucentis®), which aims to shrink and destroy the abnormal blood vessels responsible for the visual symptoms. In several trials ranibizumab has been shown to improve vision in patients with wet AMD.
It is not uncommon for patients with wet AMD to develop SMH, which when it occurs, significantly reduces the patient's visual prognosis. SMH is thought to have a number of toxic consequences on the retinal function.
This study investigates the use of two drugs: tissue plasminogen activator (tPA), a 'clot-buster' drug used to treat stroke, which is designed to dissolve the clot over the central retina (macula); and perfluoropropane (C3F8), a gas commonly used in retinal surgery, which is designed to displace the clot away from the macula.
This study is a randomized, double-masked, clinical trial with a recruitment target of 55 people with SMH and wet AMD. Participants will be allocated to one of four groups; a control group receiving none of the above drugs; one group receiving only tPA; one group receiving only C3F8; and one group receiving both. All patients will receive the 'gold-standard' treatment of ranibizumab for their underlying wet AMD. We aim to determine if tPA and/or C3F8 produce a visual outcome that is superior to standard care, with a favourable safety profile. We will also measure the size of the blood clot and scarring using computer analysis of macula photographs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control Group (A) | Sham comparator | Drug: RanibizumabRanibizumab only (active control). Participants will receive a 'sham injection' to simulate C3F8 and/or tPA administration. |
| C3F8 Only Group (B) | Experimental | Drug: Ranibizumab, Drug: C3F8 GasC3F8 given. Ranibizumab given as standard. |
| tPA and C3F8 Group (C) | Experimental | Drug: Ranibizumab, Drug: C3F8 Gas, Drug: tPABoth C3F8 gas and tPA given. Ranibizumab given as standard. |
| tPA Only Group (D) | Experimental | Drug: Ranibizumab, Drug: tPAtPA given. Ranibizumab given as standard. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults of either sex aged 50 years and older;
- SMH associated with treatment-naive or previously treated wet AMD, including retinal angiomatous proliferation (RAP) and idiopathic polypoidal choroidal vasculopathy (IPCV);
- SMH of at least 1 disc area, involving the fovea, and of sufficient density to obscure RPE detail;
- Written informed consent to participate in the study.Only one eye will be eligible for inclusion in this study.
Key exclusion criteria (15 listed)
- SMH that is known to have been present for greater than 2 weeks duration, as evidenced by history, pre-trial documentation, or fundus appearance;
- Presence of significant vitreous haemorrhage precluding accurate retinal assessment in the study eye;
- Diabetic maculopathy in the study eye;
- Visually significant cataract in the study eye;
- Amblyopia in the study eye;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanibizumabAlso: Lucentis®Single intravitreal injection of 500 micrograms ranibizumab in 0.05mls | Drug | C3F8 Only Group (B), Control Group (A), tPA Only Group (D), tPA and C3F8 Group (C) |
| C3F8 GasAlso: Perfluoropropane, Perflutren, OctafluoropropaneSingle intravitreal injection of 0.3 mls C3F8 | Drug | C3F8 Only Group (B), tPA and C3F8 Group (C) |
| tPAAlso: tissue plasminogen activator, alteplase, Actilyse®Single intravitreal injection of 50 micrograms tPA in 0.05 mls | Drug | tPA Only Group (D), tPA and C3F8 Group (C) |
Primary outcome
Mean ETDRS visual acuity
Time frame: 3 months
7 secondary outcomes
Mean ETDRS visual acuity
Time frame: 1 and 12 months
Percentage patients 15 letters or greater improvement in ETDRS visual acuity
Time frame: 12 months
Percentage patients 0 letters or greater improvement in ETDRS visual acuity
Time frame: 12 months
Percentage patients 15 letters or greater loss in ETDRS visual acuity
Time frame: 12 months
Mean total area of macular haemorrhage on colour fundus photography
Time frame: 1, 3 and 6 months
Greatest linear dimension of macular haemorrhage on colour fundus photography
Time frame: 1, 3 and 6 months
Presence of subfoveal blood on colour fundus photography
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2020.
- Derived from this study: PubMed 39418015Murphy GSP, Saleh A, Ayis S, Cheema MR, Mehta A, Steel DH, Membrey L, Costen M, Jackson TL. Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration: A Factorial Randomized Clinical Trial. JAMA Ophthalmol. 2024 Dec 1;142(12):1157-1164. doi: 10.1001/jamaophthalmol.2024.4297.
- Individual participant dataSharing planned: Undecided. The Investigator(s) and the institution(s) shall permit trial-related monitoring, audits, REC review, and regulatory inspections (where appropriate) by providing the Sponsors, Regulators and REC direct access to source data and other documents (i.e. patients' case sheets, blood test reports, X-ray reports, histology reports etc). Where necessary, inspection may also take place at the site's facilities.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy L Jackson, PhD,FRCOpht principal investigator
King's College Hospital NHS Trust
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ranibizumab, C3F8 Gas and tPA in people with Exudative Macular Degeneration and Retinal Hemorrhage, run by King's College Hospital NHS Trust at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean ETDRS visual acuity (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01835067, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2020.