GlaucomaPhase 3RAFTSNCT02767219
The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery
A Phase 3 study testing bevacizumab, 5-fluorouracil and Dexamethasone in people with Glaucoma, run by Moorfields Eye Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This is a phase III randomised controlled pilot study which aims to assess the effectiveness of the use of bevacizumab in patients who have undergone trabeculectomy surgery, which appear to be showing early signs of failure. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Glaucoma
- What is being tested?
- bevacizumab, 5-fluorouracil and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2016to May 2019
- Phase
- Phase 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 85 years, inclusive
- Patient must have undergone standard trabeculectomy augmented with Mitomycin C, within the past 4-6 weeks.
- Patients who in the clinician's opinion are mounting an aggressive wound healing response and demonstrate objective increase in bleb vascularity (moderate or severe on MBGS). Bleb function still needs to be maintained in the clinicians opinion and flat, scarred blebs are not to be included.
Who cannot join
- Unwilling or unable to give consent, unwilling to accept randomization, or unable to return for scheduled protocol visits.
- Pregnant or nursing women.
- A history of cardiovascular or cerebrovascular events in the previous 6 months, such as angina, arrhythmia, Transient Ischaemic Attack, strokes, myocardial infarction.
- Uncontrolled hypertension defined as systolic blood pressure >160millimeters of mercury (mmHg) or diastolic blood pressure >90millimeters of mercury (mmHg)
- Subject hypersensitive to bevacizumab, 5-Fluorouracil (5-FU), and Mitomycin-C (MMC) and its excipients
- Failed trabeculectomy bleb
Show all 19Show fewer
- Persistent wound leak following trabeculectomy at the time of randomisation
- The following exclusions apply to the study eye only (i.e. they may be present for the non study eye
- No light perception.
- Aphakia
- Previous, or planned, ocular surgery: vitreo-retinal, conjunctival surgery, etc considered likely to interfere with trabeculectomy outcome
- Complicated cataract surgery
- Cataract surgery less than 6 months in duration
- Secondary glaucoma, other than Pigment Dispersion Syndrome (PDS) and Pseudoexfoliative (PXF)
- Ocular trauma within the past 3 months
- Active iris neovascularization or active proliferative retinopathy.
- Severe posterior blepharitis.
- Unwilling to discontinue contact lens use after surgery.
- Current or recent (<3months) use of bevacizumab into the study eye.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Moorfields Eye Hospital, Clinical Research Facility
London, EC1V 2PD
About this study
Official title: The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery: A Single Centre Randomised Controlled Phase III Pilot Study
This is a phase III randomised controlled pilot study which aims to assess the effectiveness of the use of bevacizumab in patients who have undergone trabeculectomy surgery, which appear to be showing early signs of failure.
Read the detailed description
Pharmacological enhancement of trabeculectomy using Mitomycin C (MMC) has significantly improved success rates. Despite this, some patients still mount aggressive scarring responses post-operatively and require additional subconjunctival injections of antifibrotic agents, such as 5-Fluorouracil (5-FU) to reduce scar formation and reduce the likelihood of surgical failure. There is concern that these agents are potentially toxic and may result in side effects such as keratopathy (loss of corneal epithelium) and are also painful for the patient. For those patients that are showing clinical evidence of potential scar formation, a more predictable and less toxic modulator of wound healing is desirable.
Vascular endothelial growth factor (VEGF) has been associated with angiogenesis in numerous pathological situations, including tumor growth, proliferative retinopathy, and rheumatoid arthritis. VEGF is also thought to play a pivotal role in ocular wound healing. It mediates the signal transduction cascade leading to tenon's fibroblast migration and proliferation and collagen gel contraction at the site of surgery, as well as angiogenesis. VEGF also causes persistent vascular permeability and vasodilation at the level of existing microvessels. Vessels with increased permeability are typically tortuous and dilated and this is the clinical appearance within the conjunctiva, suggestive of future excessive wound healing and scar formation following trabeculectomy. Early interventions such as subconjunctival injections of 5-Fluorouracil (5-FU) are therefore often considered when these clinical findings are apparent, in order to modify the course of wound healing.
The investigators propose a pilot study looking at the effect of serial injections of bevacizumab (an anti-VEGF agent) on modifying the wound healing response in patients showing early signs of future failure, compared to 5-Fluorouracil (5-FU). The purpose of the pilot is to also gather outcome data and information relating to safety and recruitment with a view to powering a definitive study addressing this issue.
- Conditions
- Glaucoma
- Being tested
- bevacizumab, 5-fluorouracil, Dexamethasone
- Keywords
- Ophthalmology
- Medical subject headings
- Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
Also called Avastin
Patients will be randomised to study arms with a 1:1 ratio. Once randomised, Group 2 will receive a subconjunctival injection of bevacizumab and a subconjunctival injection of dexamethasone 3.3mg/ml. This will be given for 4 consecutive weeks from time of entry into trial.
5-fluorouracilDrug
Also called 5-FU
Patients will be randomised to study arms with a 1:1 ratio. Once randomised, Group 1 will receive a subconjunctival injection of 5-fluorouracil and a subconjunctival injection of dexamethasone 3.3mg/ml. This will be given as required for 4 consecutive weeks from time of entry into trial. This is current standard practice.
DexamethasoneDrug
Both intervention groups will be given a subconjunctival injection of dexamethasone at the time of injection of either bevacizumab or 5-fluorouracil
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone and 5-fluorouracil | Other | The control arm consists of current standard therapy of subconjunctival injections of dexamethasone 3.3mg/ml and pre filled syringes of 5-fluorouracil as required for 4 consecutive weeks after entry into the trial. Receives: Drug: 5-fluorouracil; Drug: Dexamethasone |
| Dexamethasone and Avastin | Active comparator | Subconjunctival injections of dexamethasone 3.3mg/ml and pre filled syringes of bevacizumab will be given for 4 consecutive weeks from time of entry into trial Receives: Drug: bevacizumab; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time taken to recruit 30 subjects (from start of study)
Measured: study start date to18 months
Proportion of patients who are eligible who agree to be randomized
Measured: study start date to 18 months
Proportion of patients who are lost to follow up or who withdraw from the study
Measured: Baseline to 36 months
Secondary outcomes (6)
Intraocular pressure
Measured: Baseline to 18 months
Bleb morphology (as determined by Moorfields Bleb Grading system)
Measured: Baseline to 18 months
Number of additional postoperative interventions with 5-fluorouracil (5-FU) and subconjunctival dexamethasone, following the 4 week trial intervention period; bleb needling.
Measured: received between baseline and 18 months of follow up
Time to failure
Measured: Baseline to 18 months
Number of topical ocular hypotensive medications at 3 months and 18 months
Measured: 3 months and 18 months
The incidence of complications will be recorded:
Measured: Baseline to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2016 (estimated)
- Study startMay 2016
- Primary completionFeb 2019
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlaucomaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Moorfields Eye Hospital NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rashmi Mathew, FRCOphthMBBS, Principal investigator, Moorfields Eye Hospital NHS TrustJonathan Clarke, FRCOphthMBBS, Principal investigator, Moorfields Eye Hospital NHS TrustKeith Barton, FRCOphthMBBS, Principal investigator, Moorfields Eye Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02767219
- Sponsor's protocol ID
- MATR1001
- Other IDs
- 2013-000395-15
- Acronym
- RAFTS
- Status last verified
- Aug 2021
- First submitted
- 15 Mar 2016
- Last updated
- 17 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Individual patient data will not be disclosed publically, all the data will be anonymised and analysed in accordance with the Data Protection Act
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery: A Single Centre Randomised Controlled Phase III Pilot Study
- ClinicalTrials.gov ID
- NCT02767219
- Acronym / sponsor ID
- RAFTS / MATR1001
- Conditions
- Glaucoma
- Keywords
- Ophthalmology
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Moorfields Eye Hospital NHS Foundation TrustUniversity, hospital or other
- Study start
- May 2016 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 10 May 2016 (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 is a phase III randomised controlled pilot study which aims to assess the effectiveness of the use of bevacizumab in patients who have undergone trabeculectomy surgery, which appear to be showing early signs of failure.
Detailed description
Pharmacological enhancement of trabeculectomy using Mitomycin C (MMC) has significantly improved success rates. Despite this, some patients still mount aggressive scarring responses post-operatively and require additional subconjunctival injections of antifibrotic agents, such as 5-Fluorouracil (5-FU) to reduce scar formation and reduce the likelihood of surgical failure. There is concern that these agents are potentially toxic and may result in side effects such as keratopathy (loss of corneal epithelium) and are also painful for the patient. For those patients that are showing clinical evidence of potential scar formation, a more predictable and less toxic modulator of wound healing is desirable.
Vascular endothelial growth factor (VEGF) has been associated with angiogenesis in numerous pathological situations, including tumor growth, proliferative retinopathy, and rheumatoid arthritis. VEGF is also thought to play a pivotal role in ocular wound healing. It mediates the signal transduction cascade leading to tenon's fibroblast migration and proliferation and collagen gel contraction at the site of surgery, as well as angiogenesis. VEGF also causes persistent vascular permeability and vasodilation at the level of existing microvessels. Vessels with increased permeability are typically tortuous and dilated and this is the clinical appearance within the conjunctiva, suggestive of future excessive wound healing and scar formation following trabeculectomy. Early interventions such as subconjunctival injections of 5-Fluorouracil (5-FU) are therefore often considered when these clinical findings are apparent, in order to modify the course of wound healing.
The investigators propose a pilot study looking at the effect of serial injections of bevacizumab (an anti-VEGF agent) on modifying the wound healing response in patients showing early signs of future failure, compared to 5-Fluorouracil (5-FU). The purpose of the pilot is to also gather outcome data and information relating to safety and recruitment with a view to powering a definitive study addressing this issue.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone and 5-fluorouracil | Other | Drug: 5-fluorouracil, Drug: DexamethasoneThe control arm consists of current standard therapy of subconjunctival injections of dexamethasone 3.3mg/ml and pre filled syringes of 5-fluorouracil as required for 4 consecutive weeks after entry into the trial. |
| Dexamethasone and Avastin | Active comparator | Drug: bevacizumab, Drug: DexamethasoneSubconjunctival injections of dexamethasone 3.3mg/ml and pre filled syringes of bevacizumab will be given for 4 consecutive weeks from time of entry into trial |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18 to 85 years, inclusive
- Patient must have undergone standard trabeculectomy augmented with Mitomycin C, within the past 4-6 weeks.
- Patients who in the clinician's opinion are mounting an aggressive wound healing response and demonstrate objective increase in bleb vascularity (moderate or severe on MBGS). Bleb function still needs to be maintained in the clinicians opinion and flat, scarred blebs are not to be included.
Key exclusion criteria (19 listed)
- Unwilling or unable to give consent, unwilling to accept randomization, or unable to return for scheduled protocol visits.
- Pregnant or nursing women.
- A history of cardiovascular or cerebrovascular events in the previous 6 months, such as angina, arrhythmia, Transient Ischaemic Attack, strokes, myocardial infarction.
- Uncontrolled hypertension defined as systolic blood pressure >160millimeters of mercury (mmHg) or diastolic blood pressure >90millimeters of mercury (mmHg)
- Subject hypersensitive to bevacizumab, 5-Fluorouracil (5-FU), and Mitomycin-C (MMC) and its excipients
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 |
|---|---|---|
| bevacizumabAlso: AvastinPatients will be randomised to study arms with a 1:1 ratio. Once randomised, Group 2 will receive a subconjunctival injection of bevacizumab and a subconjunctival injection of dexamethasone 3.3mg/ml. This will be given for 4 consecutive weeks from time of entry into trial. | Drug | Dexamethasone and Avastin |
| 5-fluorouracilAlso: 5-FUPatients will be randomised to study arms with a 1:1 ratio. Once randomised, Group 1 will receive a subconjunctival injection of 5-fluorouracil and a subconjunctival injection of dexamethasone 3.3mg/ml. This will be given as required for 4 consecutive weeks from time of entry into trial. This is current standard practice. | Drug | Dexamethasone and 5-fluorouracil |
| DexamethasoneBoth intervention groups will be given a subconjunctival injection of dexamethasone at the time of injection of either bevacizumab or 5-fluorouracil | Drug | Dexamethasone and 5-fluorouracil, Dexamethasone and Avastin |
Primary outcome
Time taken to recruit 30 subjects (from start of study)
Time frame: study start date to18 months
Proportion of patients who are eligible who agree to be randomized
Time frame: study start date to 18 months
Proportion of patients who are lost to follow up or who withdraw from the study
Time frame: Baseline to 36 months
6 secondary outcomes
Intraocular pressure
Time frame: Baseline to 18 months
Bleb morphology (as determined by Moorfields Bleb Grading system)
Time frame: Baseline to 18 months
Number of additional postoperative interventions with 5-fluorouracil (5-FU) and subconjunctival dexamethasone, following the 4 week trial intervention period; bleb needling.
Time frame: received between baseline and 18 months of follow up
Time to failure
Time frame: Baseline to 18 months
Number of topical ocular hypotensive medications at 3 months and 18 months
Time frame: 3 months and 18 months
The incidence of complications will be recorded:
Time frame: Baseline to 18 months
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 17 Aug 2021.
- Individual participant dataSharing planned: No. Individual patient data will not be disclosed publically, all the data will be anonymised and analysed in accordance with the Data Protection Act
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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.
Rashmi Mathew, FRCOphthMBBS principal investigator
Moorfields Eye Hospital NHS Trust
Jonathan Clarke, FRCOphthMBBS principal investigator
Moorfields Eye Hospital NHS Trust
Keith Barton, FRCOphthMBBS principal investigator
Moorfields Eye Hospital NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bevacizumab, 5-fluorouracil and Dexamethasone in people with Glaucoma, run by Moorfields Eye Hospital NHS Foundation Trust at 1 site 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 3 inclusion and 19 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 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Time taken to recruit 30 subjects (from start of study) (time frame: study start date to18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Aug 2021.