Comparison of Changes of Inflammatory Proteins in Aqueous Humour of Subjects Treated With Avastin vs Lucentis (Humour)

April 15, 2015 updated by: University of British Columbia

A Randomized, Multi-Centre, Double-Masked, Study to Compare Inflammatory Protein Changes in Aqueous Humour of Subjects Treated With Bevacizumab (Avastin) vs Ranibizumab (Lucentis) Pre-Vitrectomy for Proliferative Diabetic Retinopathy

PDR is a leading cause of irreversible vision loss in North America. This disease is caused by the growth of abnormal blood vessels in the retina. These abnormal blood vessels can bleed inside the eye, causing a vitreous hemorrhage (VH). Sometimes when patients have this bleeding, a surgery called vitrectomy is required to remove the blood from within the eye. In order to reduce complications during the surgery, most retina surgeons will inject Avastin into the eye a few days before the surgery.

Avastin (bevacizumab) is currently not approved by Health Canada to treat any ocular disease. Lucentis (ranibizumab) is approved by Health Canada as a treatment for age-related macular degeneration, diabetic macular edema, and retinal venous occlusive disease. While Avastin is not approved by Health Canada for the treatment of these diseases, the majority of retina specialists around the world are now using Avastin "off-label" to treat these diseases. That is because Avastin and Lucentis both tend to work equally well in these disease, but Avastin is significantly cheaper. While Avastin and Lucentis are generally regarded to be equal, there may be some differences between these two drugs that have not been discovered. The aim of this study is to look for these differences.

Previous research by the investigators in this study has shown that injecting Avastin into eyes causes increased inflammatory proteins to develop inside the eye. This increase in these proteins was related to complications that developed after the vitrectomy surgery. Lucentis may be associated with less of an increase in inflammatory proteins (and less complications). The aim of this study will be to compare Avastin and Lucentis with respect to how they affect inflammatory proteins in the eye, as well as the rate of complications during surgery.

Study participants will be divided into two arms ("groups") of 30 subjects. Subjects will receive Avastin or Lucentis a few days before vitrectomy surgery. The assignment will be random and the study is double-masked. Masking is done so that the investigators can clearly determine any differences between the 2 drugs.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

60 subjects will take part in this study at 2 sites in Canada: Vancouver (Eye Care Centre, Vancouver General Hospital, and Mount Saint Joseph Hospital) and Toronto (Sunnybrook Health Sciences Centre).

Study Type

Observational

Enrollment (Actual)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z3N9
        • UBC/VGH Eye Care Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

In order to assess changes in intraocular levels of cytokines following anti-VEGF treatment, the ideal time to measure these cytokines is at baseline and approximately 1 week later. In patients with PDR who are scheduled for vitrectomy, many vitreoretinal surgeons now inject bevacizumab approximately 1 week prior to the surgery in order to decrease the risk of intra-operative complications. These patients are thus an excellent study group for studying intraocular cytokine changes in response to anti-VEGF therapy, since that are already scheduled to have 2 intraocular procedures performed approximately 1 week apart, thereby minimizing the risk of obtaining aqueous humour.

Description

Inclusion Criteria:

1. PDR and vitreous hemorrhage scheduled for vitrectomy surgery and bevacizumab pre-treatment.

Exclusion criteria:

  1. Vitreous hemorrhage from other causes such as central retinal vein occlusion or ocular ischemic syndrome.
  2. Pregnant or breastfeeding women.
  3. Less than 19 years of age.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PDR, Avastin/Lucentis, randomization, humour, inflamation
Patients will be randomized to receive pre-treatment with either bevacizumab or ranibizumab . Sample of aqueous humour will be taken before injection and before surgery.Both the patient and the treating physician will be masked to the identity of the study drug.
Other: Injection of Avastin / Lucentis, sampling aqueous humour

Study participants will be divided into two arms. Subjects will receive Avastin or Lucentis a few days before vitrectomy surgery. The assignment will be double-masked.The first sample of aqueous humor will be obtained immediately prior to the intravitreal injection.

On the same of the intravitreal injection, a blood sample will be taken for hemoglobin A1C measurement. Approximately 1 week later when patients are having their scheduled vitrectomy surgery, an additional sample of aqueous humour will be obtained .

Intraocular cytokines levels will be measured in aqueous humor samples using multiplex cytokine assays.

Other Names:
  • Lucentis
  • Avastin
  • Humour
  • Inflamatory Cytokines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary outcome will be the change in global levels of intraocular inflammatory cytokines in the aqueous humour of patients with Proliferative Diabetic Retinopathy.
Time Frame: Baseline and two weeks
No single inflammatory cytokine or any summary measure of the cytokines has been shown to characterize the effect of anti-VEGF (Vascular Endothelial Growth Factor)treatment; therefore, we will employ a global test to compare the difference of all inflammatory cytokines between the two treatment groups. For each cytokine the endpoint will be defined as percentage change from baseline. We will employ O'Brien's rank-sum global test to simultaneously evaluate all the inflammatory cytokine endpoints. O'Brien's test is a nonparametric test procedure for testing whether multiple outcomes in one treatment group have consistently larger values than outcomes in the other treatment group.
Baseline and two weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary outcomes include the change in angiogenic cytokine levels.
Time Frame: Baseline and two weeks
Study outcomes will be analyzed using multivariate models, and covariates will include age, gender, diabetes type, hemoglobin A1C (glycosilated hemoglobin)level, and the number of days between the time of anti-VEGF pretreatment and vitrectomy.
Baseline and two weeks
Secondary outcome measure considers intraoperative complications during vitrectomy.
Time Frame: Baseline and two weeks
The following intra-operative data will be recorded: use of adjunctive intravitreal/periocular triamcinolone (Kenalog®,)presence of tractional retinal detachment, occurrence of intra-operative bleeding and iatrogenic tears, use of endodiathermy/endolaser, and mean surgical time.
Baseline and two weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Investigators

  • Principal Investigator: Farzin Forooghian, MD FRCSC, Clinical Assistant Professor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

December 14, 2012

First Submitted That Met QC Criteria

January 2, 2013

First Posted (Estimate)

January 4, 2013

Study Record Updates

Last Update Posted (Estimate)

April 16, 2015

Last Update Submitted That Met QC Criteria

April 15, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H11-02704

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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