- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02767219
The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery (RAFTS)
The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery: A Single Centre Randomised Controlled Phase III Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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London, United Kingdom, EC1V 2PD
- Moorfields Eye Hospital, Clinical Research Facility
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Dexamethasone and 5-fluorouracil
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.
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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.
Other Names:
Both intervention groups will be given a subconjunctival injection of dexamethasone at the time of injection of either bevacizumab or 5-fluorouracil
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Active Comparator: Dexamethasone and Avastin
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
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Both intervention groups will be given a subconjunctival injection of dexamethasone at the time of injection of either bevacizumab or 5-fluorouracil
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time taken to recruit 30 subjects (from start of study)
Time Frame: study start date to18 months
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study start date to18 months
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Proportion of patients who are eligible who agree to be randomized
Time Frame: study start date to 18 months
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study start date to 18 months
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Proportion of patients who are lost to follow up or who withdraw from the study
Time Frame: Baseline to 36 months
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Baseline to 36 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Intraocular pressure
Time Frame: Baseline to 18 months
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Baseline to 18 months
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Bleb morphology (as determined by Moorfields Bleb Grading system)
Time Frame: Baseline to 18 months
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Baseline to 18 months
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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
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received between baseline and 18 months of follow up
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Time to failure
Time Frame: Baseline to 18 months
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Baseline to 18 months
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Number of topical ocular hypotensive medications at 3 months and 18 months
Time Frame: 3 months and 18 months
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3 months and 18 months
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The incidence of complications will be recorded:
Time Frame: Baseline to 18 months
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Baseline to 18 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Rashmi Mathew, FRCOphthMBBS, Moorfields Eye Hospital NHS Trust
- Principal Investigator: Jonathan Clarke, FRCOphthMBBS, Moorfields Eye Hospital NHS Trust
- Principal Investigator: Keith Barton, FRCOphthMBBS, Moorfields Eye Hospital NHS Trust
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Eye Diseases
- Ocular Hypertension
- Glaucoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dexamethasone
- Fluorouracil
- Bevacizumab
Other Study ID Numbers
- MATR1001
- 2013-000395-15 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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