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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of British Columbia
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01760746
First received: December 14, 2012
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • Secondary outcomes include the change in angiogenic cytokine levels. [ Time Frame: Baseline and two weeks ] [ Designated as safety issue: No ]
    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.

  • Secondary outcome measure considers intraoperative complications during vitrectomy. [ Time Frame: Baseline and two weeks ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 60
Study Start Date: July 2012
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
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.

Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01760746

Contacts
Contact: David A Albiani, MD FRCSC 604-875-4253 david_albiani@yahoo.com
Contact: Andrew W Kirker, MD FRCSC 604-875-4253 awkirker@gmail.com

Locations
Canada, British Columbia
UBC/VGH Eye Care Centre Recruiting
Vancouver, British Columbia, Canada, V5Z3N9
Contact: Aleksandra Kuzmanovic, MSc    604-875-4254    aleksandra.kuzmanovic@vch.ca   
Contact: Marie Punzalan, CCRP    604-875-4111 ext 21726    marie.punzalan@vch.ca   
Sub-Investigator: David A Albiani, MD FRCSC         
Sub-Investigator: Andrew B Merkur, MD FRCSC         
Sub-Investigator: Andrew W Kirker, MD FRCSC         
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Farzin Forooghian, MD FRCSC Clinical Assistant Professor
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01760746     History of Changes
Other Study ID Numbers: H11-02704
Study First Received: December 14, 2012
Last Updated: January 2, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
Proliferative Diabetic Retinopathy
Vitrectomy
Inflammatory Cytokines

Additional relevant MeSH terms:
Diabetic Retinopathy
Retinal Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Endocrine System Diseases
Eye Diseases
Vascular Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014