Efficacy and Safety Trial of Intravitreal Injections Combined With PRP for the Treatment of CSME Secondary to Diabetes Mellitus (DAVE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Greater Houston Retina Research
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
David M. Brown, M.D., Greater Houston Retina Research
ClinicalTrials.gov Identifier:
NCT01552408
First received: February 28, 2012
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

This study is a Phase I/II, multicenter, randomized, study of the efficacy and safety of ranibizumab injection monotherapy verses a duel therapy of 0.3mg ranibizumab combined with ultra wide, 200° field angiography guided pan retinal photocoagulation in patients with CSME-CI secondary to diabetes mellitus (Type 1 or 2).


Condition Intervention Phase
Diabetic Macular Edema
Drug: 0.30mg ranibizumab
Procedure: Targeted Pan Retinal Photocoagulation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Randomized, Study for Diabetic Macular Edema Using 0.3mg Ranibizumab Combined With Targeted PRP Monthly for 4 Months,Then PRN vs. 0.3mg Ranibizumab 4 Months Monotherapy, Then as Needed(DME-AntiVEgf) DAVE

Resource links provided by NLM:


Further study details as provided by Greater Houston Retina Research:

Primary Outcome Measures:
  • Assess the total number of ranibizumab injections in each of the two cohorts in a 24 month period [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Assess number of ranibizumab injections in each of the two cohorts required through Month 24.


Secondary Outcome Measures:
  • Determine percentage of patients who experience a gain of 15 or more letters from baseline in ETDRS BCVA. [ Time Frame: 24Months ] [ Designated as safety issue: No ]
    Determine percentage of patients who experience a gain of 15 or more letters from baseline to Month 24 in ETDRS BCVA.

  • Evaluate mean change in central retinal thickness over time as assessed by high resolution OCTs [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Evaluate mean change in central retinal thickness over time through Month 24 as assessed by high resolution OCTs

  • Percentage of patients with persistent macular edema post intravitreal injection [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Mean change in peripheral visual field as measured by Goldmann visual field [ Time Frame: 6 and 12, 24 Months ] [ Designated as safety issue: No ]
    Mean change in peripheral visual field as measured by Goldmann visual field at screen, month 6 and month 12 and 24 months


Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 0.30mg ranibizumab
4 mandatory monthly injections of 0.30mg ranibizumab,retreatment will be as needed
Drug: 0.30mg ranibizumab
Cohort 1- will receive 4 mandatory monthly injections, then will be seen monthly and retreatment will be as needed, as defined by retreatment criteria
Other Name: Lucentis
Experimental: Targeted PRP with 0.30mg Ranibizumab
4 mandatory monthly injections of 0.30mg Ranibizumab, and at V3 (day7) will receive Targeted PRP, then treatment with Ranibizumab will be prn
Procedure: Targeted Pan Retinal Photocoagulation
Cohort 2- will receive 4 mandatory monthly injections, and at V3 (day7) will receive approx 800 to 2400 applications laser (Pan Retinal Photocoagulation) as guided by Ultra wide 200° field angiography, then will be seen monthly and retreatment will be as needed, as defined by retreatment criteria, if the subject still has area of peripheral ischemia after loding dose of drug, then an second laser treatment will be applied
Other Names:
  • PRP
  • Laser Photocoagulation
  • Pan Retinal Photocoagulation

Detailed Description:

Approximately 40 eyes will be randomized at 3 investigational centers in the United States. This study consists of a screening period of up to 14 days (Days -14 to -1), and a 12-month treatment period (Day 0 to Month 12). Subjects who provide consent will enter the screening period to determine eligibility. As part of the screening process, the examining investigator will evaluate the macular foveal avascular zone fluorescein images to determine subjects' eligibility. Eligible subjects will be randomized in a 1:1 ratio so that approximately 20 eyes will receive 0.3 mg ranibizumab monotherapy, and approximately 20 eyes will receive 0.3 mg ranibizumab combined with Ultra wide 200° field angiogram guided pan retinal photocoagulation. Subjects must meet VA and retinal thickness eligibility requirements during both the screening period (as confirmed by the eligibility panel). The subject can have both eyes in the study if both are eligible at the time of randomization. If both eyes are eligible, one eye will be randomized, to cohort 1 while the other eye will be randomized to the cohort 2. A subject with both eyes in the trial will have each eye in a separate cohort.

If both subject eyes are enrolled in the trial, the treatment interval should be no less than 3 days and no longer than 10 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willingness to provide signed informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
  • Age ≥ 18 years
  • Diabetes Mellitus (Type 1 or 2) The following will be considered as sufficient evidence that diabetes is present:
  • Current regular use of insulin for the treatment of diabetes
  • Current regular use of oral ant hyperglycemic agents for the treatment of diabetes
  • Documented diabetes according to the American Diabetes Association and /or World Health Organization criteria
  • BCVA score in the study eye of 20/32 to 20/200 approximate snellen equivalent using the ETDRS protocol at an initial testing distance of 4 meters, confirmed by the investigator
  • High Definition OCT(Spectralis) central thickness measurement of ≥ 300μ
  • Decrease in visual acuity is determined to be primarily the result of DME and not to other cause
  • Ability and willingness to return for all scheduled visits and assessments

Exclusion Criteria:

  • Participation in another simultaneous medical investigation or trial

    • Prior Ocular Treatment
    • History of vitrectomy surgery in the study eye
    • Any pan retinal photocoagulation in the study eye
    • Prior treatment with intraocular or subconjunctival steroids in the study eye 4 months prior to screen
    • Previous treatment with anti angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc) within 2 months of Day 0 visit
    • systemic corticosteroids 4 months prior to screen
  • Any concurrent intraocular condition in the study eye (e.g., cataract or age related macular degeneration) that, in the opinion of the investigator, could either:

    • Require medical or surgical intervention during the 12-month study period to prevent or treat visual loss that might result from that condition; or if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of BCVA over the 12-month study period.
    • Active intraocular inflammation (grade trace or above) in the study eye
    • Current vitreous hemorrhage in the study eye
    • History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
    • Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
    • Uncontrolled glaucoma in the study eye (defined as IOP ≥ 30 mmHg despite treatment with anti-glaucoma medication)
    • History of corneal transplant in the study eye
    • High Risk PDR: New vessels within one disc diameter of the optic nerve head that are larger than one-third disc area
    • Vitreous or preretinal hemorrhage associated with less extensive NVD or with NVE one-half disc area or more in size
    • Extensive damage to the fovea vascular zone as determined by the photographic reading panel
    • Spherical equivalent of the refractive error in the study eye of more than -8.00 diopter of myopia
    • Vitreomacular traction (vitreomacular attachment ok)
    • Uncontrolled blood pressure (defined as systolic > 180 mmHg and/or diastolic > 110 mmHg while patient is sitting)
    • Atrial fibrillation not managed by patient's primary care physician or cardiologist within 3 months of screening visit
    • History of stroke within the last 3 months of screening visit
    • History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications
    • Current treatment for active systemic infection
    • Active malignancy
    • History of allergy to fluorescein, not amenable to treatment
    • Inability to comply with study or follow-up procedures
    • Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)
  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: NCT01552408

Contacts
Contact: David M Brown, MD 713-524-3434 dmbmd@houstonretina.com
Contact: Karri L Schuetzle 713-394-7534 karri.schuetzle@houstonretina.com

Locations
United States, Texas
Retina Consultants of Houston Recruiting
Houston, Texas, United States, 77030
Contact: Karri L Schuetzle    713-394-7534    karri.schuetzle@houstonretina.com   
Principal Investigator: David M Brown, MD         
Sub-Investigator: Tien P Wong, MD         
Sub-Investigator: Matthew S Benz, MD         
Sub-Investigator: James C Major, MD         
Sub-Investigator: Richard H Fish, MD         
Sub-Investigator: Charles C Wykoff, MD         
Sub-Investigator: Eric Chen, MD         
Sub-Investigator: Rosa Y Kim, MD         
Sub-Investigator: Amy C Schefler, MD         
Sponsors and Collaborators
David M. Brown, M.D.
Genentech
Investigators
Principal Investigator: David M Brown, MD Director Greater Houston Research
  More Information

Publications:

Responsible Party: David M. Brown, M.D., Director Greater Houston Retina Research, Greater Houston Retina Research
ClinicalTrials.gov Identifier: NCT01552408     History of Changes
Other Study ID Numbers: ML27954
Study First Received: February 28, 2012
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Greater Houston Retina Research:
Non Proliferative Diabetic Retinopathy
Diabetic Retinopathy
Macular Edema
Background Diabetic Retinopathy
Pre Proliferative Diabetic Retinopathy

Additional relevant MeSH terms:
Edema
Macular Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on July 28, 2014