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.
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

February 28, 2012
October 7, 2013
March 2012
March 2014   (final data collection date for primary outcome measure)
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.
Assess the total number of ranibizumab injections in each of the two cohorts in a 12 month period [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
Assess number of ranibizumab injections in each of the two cohorts required through Month 12.
Complete list of historical versions of study NCT01552408 on ClinicalTrials.gov Archive Site
  • 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
  • Determine percentage of patients who experience a gain of 15 or more letters from baseline in ETDRS BCVA. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Determine percentage of patients who experience a gain of 15 or more letters from baseline to Month 12 in ETDRS BCVA.
  • Evaluate mean change in central retinal thickness over time as assessed by high resolution OCTs [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Evaluate mean change in central retinal thickness over time through Month 12 as assessed by high resolution OCTs
  • Percentage of patients with persistent macular edema post intravitreal injection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Mean change in peripheral visual field as measured by Goldmann visual field [ Time Frame: 6 and 12 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
Not Provided
Not Provided
 
Efficacy and Safety Trial of Intravitreal Injections Combined With PRP for the Treatment of CSME Secondary to Diabetes Mellitus (DAVE)
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

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).

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Diabetic Macular Edema
  • 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
  • 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
  • Active Comparator: 0.30mg ranibizumab
    4 mandatory monthly injections of 0.30mg ranibizumab,retreatment will be as needed
    Intervention: Drug: 0.30mg ranibizumab
  • 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
    Intervention: Procedure: Targeted Pan Retinal Photocoagulation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
March 2014
March 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact: David M Brown, MD 713-524-3434 dmbmd@houstonretina.com
Contact: Karri L Schuetzle 713-394-7534 karri.schuetzle@houstonretina.com
United States
 
NCT01552408
ML27954
Yes
David M. Brown, M.D., Greater Houston Retina Research
David M. Brown, M.D.
Genentech
Principal Investigator: David M Brown, MD Director Greater Houston Research
Greater Houston Retina Research
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP