The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery

NCT02767219 | Completed Phase 3 DMC

• 2 other identifiers: MATR10012013-000395-15
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glaucoma

Keywords

Ophthalmology

Outcome Measures

Primary Outcomes (3)

• Time taken to recruit 30 subjects (from start of study)

  study start date to18 months

• Proportion of patients who are eligible who agree to be randomized

  study start date to 18 months

• Proportion of patients who are lost to follow up or who withdraw from the study

  Baseline to 36 months

Secondary Outcomes (6)

• Intraocular pressure

  Baseline to 18 months

• Bleb morphology (as determined by Moorfields Bleb Grading system)

  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.

  received between baseline and 18 months of follow up

• Time to failure

  Baseline to 18 months

• Number of topical ocular hypotensive medications at 3 months and 18 months

  3 months and 18 months

Study Arms (2)

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.

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

Drug: bevacizumab; Drug: Dexamethasone

Interventions

bevacizumab DRUG

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.

Also known as: Avastin

Dexamethasone and Avastin

5-fluorouracil DRUG

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.

Also known as: 5-FU

Dexamethasone and 5-fluorouracil

Dexamethasone DRUG

Both intervention groups will be given a subconjunctival injection of dexamethasone at the time of injection of either bevacizumab or 5-fluorouracil

Dexamethasone and 5-fluorouracil; Dexamethasone and Avastin

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Moorfields Eye Hospital NHS Foundation Trust: lead

Study Sites (1)

Moorfields Eye Hospital, Clinical Research Facility

London, EC1V 2PD, United Kingdom

Location

MeSH Terms

Conditions

Glaucoma

Interventions

Bevacizumab; Fluorouracil; Dexamethasone

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

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: March 15, 2016
• First Posted: May 10, 2016
• Study Start: May 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: May 1, 2019
• Last Updated: August 17, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)