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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01760746
Recruitment Status : Completed
First Posted : January 4, 2013
Last Update Posted : April 16, 2015
Information provided by (Responsible Party):
University of British Columbia

Brief Summary:

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.

Condition or disease Intervention/treatment
Proliferative Diabetic Retinopathy (PDR) Other: Injection of Avastin / Lucentis, sampling aqueous humour

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).

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Study Type : Observational
Actual Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: 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
Study Start Date : July 2012
Actual Primary Completion Date : October 2013
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Ranibizumab

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:
  • Humour
  • Inflamatory Cytokines
  • Avastin
  • Lucentis

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

Biospecimen Retention:   Samples Without DNA
Aqueous humour

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01760746

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Canada, British Columbia
UBC/VGH Eye Care Centre
Vancouver, British Columbia, Canada, V5Z3N9
Sponsors and Collaborators
University of British Columbia
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Principal Investigator: Farzin Forooghian, MD FRCSC Clinical Assistant Professor
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Responsible Party: University of British Columbia Identifier: NCT01760746    
Other Study ID Numbers: H11-02704
First Posted: January 4, 2013    Key Record Dates
Last Update Posted: April 16, 2015
Last Verified: April 2015
Keywords provided by University of British Columbia:
Proliferative Diabetic Retinopathy
Inflammatory Cytokines
Additional relevant MeSH terms:
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Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors