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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech, Inc.
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: August 11, 2014
Last verified: August 2014
  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: 0.3 mg 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 36 month period [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Assess number of ranibizumab injections in each of the two cohorts required through Month 36.

  • Evaluate the mean change over time in ETDRS BCVA through Month 36 [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Evaluate the mean change over time in ETDRS BCVA through Month 36

  • Incidence and severity of ocular and non-ocular adverse events (AE's) through Month 36. [ Time Frame: 36 Months ] [ Designated as safety issue: Yes ]
    Incidence and severity of ocular and non-ocular adverse events (AE's) through Month 36.


Secondary Outcome Measures:
  • Percentage of patients who experience a loss of 15 or more letters from Baseline to Month 12, 24, and 36 in ETDRS BCVA. [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Percentage of patients who experience a loss of 15 or more letters from Baseline to Month 12, 24, and 36 in ETDRS BCVA.

  • Determine percentage of patients who experience a gain of 15 or more letters from Baseline to Month 12, 24, and 36 in ETDRS BCVA [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Determine percentage of patients who experience a gain of 15 or more letters from Baseline to Month 12, 24, and 36 in ETDRS BCVA

  • Evaluate mean change in central retinal thickness over time through Month 12, 24, and 36 as assessed by high resolution OCT's. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Evaluate mean change in central retinal thickness over time through Month 12, 24, and 36 as assessed by high resolution OCT's.

  • Percentage of patients with persistent macular edema post-intravitreal injection. [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Percentage of patients with persistent macular edema post-intravitreal injection.

  • Mean change in peripheral visual field as measured by Goldmann visual field at screen and Months 12, 24, and 36. [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Mean change in peripheral visual field as measured by Goldmann visual field at screen and Months 12, 24, and 36.


Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 0.3 mg Ranibizumab
Cohort 1: Subjects will receive 4 mandatory intravitreal injections of 0.3 mg ranibizumab every 28 days (+/- 7 days). They will then be seen monthly (+/- 7 days) and will receive intravitreal injections of 0.3 mg ranibizumab on a PRN schedule per retreatment criteria based on the evaluating Investigator's assessment of disease activity.
Drug: 0.3 mg ranibizumab
Cohort 1: Subjects will receive 4 mandatory intravitreal injections of 0.3 mg ranibizumab every 28 days (+/- 7 days). They will then be seen monthly (+/- 7 days) and will receive intravitreal injections of 0.3 mg ranibizumab on a PRN schedule per retreatment criteria based on the evaluating Investigator's assessment of disease activity.
Other Name: Lucentis
Experimental: Targeted PRP with 0.3 mg Ranibizumab
Cohort 2: Subjects will receive 4 mandatory intravitreal injections of 0.3 mg ranibizumab every 28 days (+/- 7 days). They will then be seen monthly (+/- 7 days) and will receive intravitreal injections of 0.3 mg ranibizumab on a PRN schedule per retreatment criteria based on the evaluating Investigator's assessment of disease activity. In addition, at V3 (Day 7) they will receive targeted pan-retinal photocoagulation (PRP) based on ultra wide 200º field angiography. After the first session of PRP, subject's will have ultra wide 200º field angiography performed every 3 months to indicate areas of peripheral ischemia, which will be selectively treated at V9 (Month 6), V21 (Month 18), and V28 (Month 25), preserving areas of more perfused retina. This will minimize any visual field loss secondary to nonselective pan-retinal photocoagulation.
Procedure: Targeted Pan Retinal Photocoagulation
Cohort 2: Subjects will receive 4 mandatory intravitreal injections of 0.3 mg ranibizumab every 28 days (+/- 7 days). They will then be seen monthly (+/- 7 days) and will receive intravitreal injections of 0.3 mg ranibizumab on a PRN schedule per retreatment criteria based on the evaluating Investigator's assessment of disease activity. In addition, at V3 (Day 7) they will receive targeted pan-retinal photocoagulation (PRP) based on ultra wide 200º field angiography. After the first session of PRP, subject's will have ultra wide 200º field angiography performed every 3 months to indicate areas of peripheral ischemia, which will be selectively treated at V9 (Month 6), V21 (Month 18), and V28 (Month 25), preserving areas of more perfused retina. This will minimize any visual field loss secondary to nonselective pan-retinal photocoagulation.
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 36-month treatment period (Day 0 to Month 36). 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 the screening period. The subject can have both eyes in the study. 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.

  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 antihyperglycemic 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 20/320 approximate snellen equivalent using the ETDRS protocol at an initial testing distance of 4 meters, confirmed by the investigator.
  • High Definition OCT (Spectralis) central retinal thickness measurement of ≥ 300 µm
  • 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.
  • Clear ocular media and adequate pupillary dilatation to permit good quality fundus photography.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from this study:

General Exclusion Criteria

  • Pregnancy (positive pregnancy test) or lactation
  • Sexually active women of childbearing potential* who are unwilling to practice adequate contraception or abstinence during the study. (*Although no birth control method is 100% effective, the following are considered adequate means of contraception: surgical sterilization, use of oral contraceptives, barrier contraception using either a condom or diaphragm with spermicidal gel, intrauterine devices, or contraceptive hormone implants or patches. A subject's primary care physician, obstetrician, or gynecologist should be consulted regarding an appropriate form of birth control)
  • Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
  • Participation in another simultaneous medical investigation or trial] Ocular Exclusion Criteria
  • 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 antiangiogenic 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

Concurrent Ocular Conditions:

  • Any concurrent ocular condition in the study eye (e.g., cataract or age-related macular degeneration) that, in the opinion of the investigator could: require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition; or, if allowed to progress untreated, could likely contribute to a loss of at least 2 Snellen equivalent lines of BCVA over the 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
  • Aphakia or absence of the posterior capsule in the study eye
  • Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0
  • Uncontrolled glaucoma in the study eye (defined as IOP ≥ 30 mmHg despite treatment with anti-glaucoma medication)
  • History of glaucoma-filtering surgery in the study eye
  • 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 principal investigator or designated site personnel
  • Spherical equivalent of the refractive error in the study eye of more that -8.00 diopter of myopia
  • Vitreomacular traction (vitreomacular attachment ok) Concurrent Systemic Conditions
  • Uncontrolled blood pressure (defined as systolic > 180 mmHg and/or diastolic > 110 mmHg while patient is seated. *If a subject's initial reading exceeds these values, a second reading may be taken 30 or more minutes later. If the subject's blood pressure needs to be controlled by antihypertensive medication, the subject can become eligible if medication is taken continuously for at least 30 days prior to Day 0
  • Atrial fibrillation not managed by subject'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 of an investigational drug or that might affect the 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 obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded.
  • 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

Locations
United States, Texas
Retina Consultants of Houston
Houston, Texas, United States, 77030
Retina Consultants of Houston
Katy, Texas, United States, 77494
Retina Consultants of Houston
The Woodlands, Texas, United States, 77384
Sponsors and Collaborators
David M. Brown, M.D.
Genentech, Inc.
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: August 11, 2014
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
Eye Diseases
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on November 24, 2014