Diabetic Macular EdemaPhase 1/2DAVENCT01552408
Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE)
A Phase 1/2 study testing 0.3 mg ranibizumab and Targeted Pan Retinal Photocoagulation in people with Diabetic Macular Edema, run by David M. Brown, M.D. at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- 0.3 mg ranibizumab and Targeted Pan Retinal Photocoagulation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2012to 18 May 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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
Show all 37Show fewer
- 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)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Retina Consultants of Houston
Houston, Texas, 77030
Retina Consultants of Houston
Katy, Texas, 77494
Retina Consultants of Houston
The Woodlands, Texas, 77384
About this study
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
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).
Read the 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 targeted pan retinal photocoagulation (PRP). 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.
- Conditions
- Diabetic Macular Edema
- Being tested
- 0.3 mg ranibizumab, Targeted Pan Retinal Photocoagulation
- Keywords
- Non Proliferative Diabetic Retinopathy, Diabetic Retinopathy, Macular Edema, Background Diabetic Retinopathy, Pre Proliferative Diabetic Retinopathy
- Medical subject headings
- Diabetic Retinopathy, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.3 mg ranibizumabDrug
Also called Lucentis
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.
Targeted Pan Retinal PhotocoagulationProcedure or surgery
Also called PRP, Laser Photocoagulation, 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.
| Study group | Role | What they receive |
|---|---|---|
| 0.3 mg Ranibizumab | Active comparator | Cohort 1: Subjects will receive 4 IVT of 0.3 mg ranibizumab every 28 days (+/- 7 days), then will be seen monthly (+/- 7 days) \& will receive IVT of 0.3 mg ranibizumab on a pro re nata (PRN) schedule per retreatment criteria. Receives: Drug: 0.3 mg ranibizumab |
| Targeted PRP with 0.3 mg Ranibizumab | Experimental | Cohort 2: Subjects will receive 4 it of 0.3 mg ranibizumab every 28 days (+/- 7 days), then will then be seen monthly (+/- 7 days) \& receive IVT 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 Day 7 they will receive targeted pan-retinal photocoagulation (PRP) based on ultra wide field angiography. Ultra wide field angiography will be performed every 3 months to indicate areas of peripheral ischemia, which will be selectively be treated with PRP at Month 6, Month 18, and Month 25, preserving areas of more perfused retina. Receives: Drug: 0.3 mg ranibizumab; Procedure: Targeted Pan Retinal Photocoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Ranibizumab Injections in Each of the Two Cohorts in a 36 Month Period
Assess the number of ranibizumab injections in the ranibizumab and targeted panretinal photocoagulation (PRP) with ranibizumab cohorts through Month 36.
Measured: 36 Months
Mean Change Over Time in Early Treatment Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS BCVA) Through Month 36
Evaluate the mean change over time in ETDRS BCVA in the ranibizumab and targeted PRP with ranibizumab cohorts through Month 36.
Measured: 36 Months
Incidence and Severity of Ocular and Non-ocular Adverse Events (AE's) Through Month 36.
Incidence and severity of ocular and non-ocular adverse events (AE's) in the monotherapy and combination cohorts through Month 36.
Measured: 36 Months
Secondary outcomes (5)
Patients Who Experience a Loss of 15 or More Letters From Baseline to Month 12, 24, and 36 in ETDRS BCVA.
Percentage of patients in the ranibizumab and targeted PRP with ranibizumab cohorts who experience a loss of 15 or more letters from Baseline to Month 12, 24, and 36 in ETDRS BCVA.
Measured: Month 12, 24, and 36
Determine Percentage of Patients Who Experience a Gain 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 in the ranibizumab and targeted PRP with ranibizumab cohorts.
Measured: Month 12, 24, and 36
Evaluate Mean Change in Central Retinal Thickness Over Time Through Month 12, 24, and 36 as Assessed by High Resolution OCT's.
Evaluate mean change in central retinal thickness in the ranibizumab and targeted PRP with ranibizumab cohorts over time through Month 12, 24, and 36 as assessed by high resolution OCT's.
Measured: Month 12, 24, and 36
Patients With Persistent Macular Edema Post-intravitreal Injection.
Percentage of patients with persistent macular edema post-intravitreal injection in the ranibizumab and targeted PRP with ranibizumab cohorts.
Measured: Month 36
Mean Change in Peripheral Visual Field as Measured by Goldmann Visual Field at Screen and Month and 36.
Mean change in peripheral visual field as measured by Goldmann visual field at screen and Month 36 in the ranibizumab and targeted PRP with ranibizumab cohorts.
Measured: 36 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2012 (estimated)
- Study startMar 2012
- Primary completion18 May 2017
- Study completion18 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- David M. Brown, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor-investigator, David M. Brown, M.D., Greater Houston Retina Research
- Investigators
- David M Brown, MD, Principal investigator, Director Greater Houston Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01552408
- Sponsor's protocol ID
- ML27954
- Acronym
- DAVE
- Status last verified
- Oct 2018
- First submitted
- 28 Feb 2012
- Last updated
- 5 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Klein R, Meuer SM, Moss SE, Klein BE. Retinal microaneurysm counts and 10-year progression of diabetic retinopathy. Arch Ophthalmol. 1995 Nov;113(11):1386-91. doi: 10.1001/archopht.1995.01100110046024.
PubMed 7487599Klein M. Prevention and treatment of the complications of diabetes mellitus. N Engl J Med. 1995 Sep 21;333(12):802. doi: 10.1056/NEJM199509213331215. No abstract available.
PubMed 7643896Cruickshanks KJ, Moss SE, Klein R, Klein BE. Physical activity and the risk of progression of retinopathy or the development of proliferative retinopathy. Ophthalmology. 1995 Aug;102(8):1177-82. doi: 10.1016/s0161-6420(95)30893-7.
PubMed 9097744Diabetic Retinopathy Clinical Research Network; Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK, Elman MJ, Friedman SM, Greven CM, Maturi RK, Pieramici DJ, Shami M, Singerman LJ, Stockdale CR. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology. 2007 Oct;114(10):1860-7. doi: 10.1016/j.ophtha.2007.05.062. Epub 2007 Aug 15.
PubMed 17698196Writing Committee for the Diabetic Retinopathy Clinical Research Network; Fong DS, Strauber SF, Aiello LP, Beck RW, Callanan DG, Danis RP, Davis MD, Feman SS, Ferris F, Friedman SM, Garcia CA, Glassman AR, Han DP, Le D, Kollman C, Lauer AK, Recchia FM, Solomon SD. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007 Apr;125(4):469-80. doi: 10.1001/archopht.125.4.469.
PubMed 17420366From the NIH: Study identifies four factors in diabetic retinopathy associated with high risk of severe visual loss. JAMA. 1979 Apr 13;241(15):1581. No abstract available.
PubMed 581885Four risk factors for severe visual loss in diabetic retinopathy. The third report from the Diabetic Retinopathy Study. The Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1979 Apr;97(4):654-5. doi: 10.1001/archopht.1979.01020010310003.
PubMed 426679Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806.
PubMed 2866759Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1987 Jul;94(7):761-74. doi: 10.1016/s0161-6420(87)33527-4.
PubMed 3658348Muggeo M. DCCT and us: how far are we from implementation? Acta Diabetol. 1993;30(3):115-7. doi: 10.1007/BF00572852. No abstract available.
PubMed 8111068Luddeke HJ. [Continuing education provided by the Diabetes Society. Results of the UKPDS (United Kingdom Diabetes Society) and therapeutic guidelines concerning diabetes type II]. Fortschr Med. 1998 Nov 30;116(33):35-8. No abstract available. German.
PubMed 9889462Watkins P. The UKPDS. A model for gathering the evidence for the management of chronic diseases. UK Prospective Diabetes Study Group. J R Coll Physicians Lond. 1998 Nov-Dec;32(6):510-1. No abstract available.
PubMed 9881303Diabetic Retinopathy Clinical Research Network (DRCR.net); Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009 Mar;127(3):245-51. doi: 10.1001/archophthalmol.2008.610.
PubMed 19273785Scott IU, Danis RP, Bressler SB, Bressler NM, Browning DJ, Qin H; Diabetic Retinopathy Clinical Research Network. Effect of focal/grid photocoagulation on visual acuity and retinal thickening in eyes with non-center-involved diabetic macular edema. Retina. 2009 May;29(5):613-7. doi: 10.1097/IAE.0b013e3181a2c07a.
PubMed 19373126Jonas JB, Strueven V, Kamppeter BA, Harder B, Spandau UH, Schlichtenbrede F. Visual acuity change after intravitreal triamcinolone in various types of exudative age-related macular degeneration. J Ocul Pharmacol Ther. 2006 Oct;22(5):370-6. doi: 10.1089/jop.2006.22.370.
PubMed 17076632
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01552408
- Acronym / sponsor ID
- DAVE / ML27954
- Conditions
- Diabetic Macular Edema
- Keywords
- Non Proliferative Diabetic Retinopathy, Diabetic Retinopathy, Macular Edema, Background Diabetic Retinopathy, Pre Proliferative Diabetic Retinopathy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- David M. Brown, M.D.University, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Mar 2012 (actual)
- Primary completion
- 18 May 2017 (actual)
- Study completion
- 18 May 2017 (actual)
- First posted
- 13 Mar 2012 (estimated)
- Results
- Posted 14 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 targeted pan retinal photocoagulation (PRP). 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.3 mg Ranibizumab | Active comparator | Drug: 0.3 mg ranibizumabCohort 1: Subjects will receive 4 IVT of 0.3 mg ranibizumab every 28 days (+/- 7 days), then will be seen monthly (+/- 7 days) \& will receive IVT of 0.3 mg ranibizumab on a pro re nata (PRN) schedule per retreatment criteria. |
| Targeted PRP with 0.3 mg Ranibizumab | Experimental | Drug: 0.3 mg ranibizumab, Procedure: Targeted Pan Retinal PhotocoagulationCohort 2: Subjects will receive 4 it of 0.3 mg ranibizumab every 28 days (+/- 7 days), then will then be seen monthly (+/- 7 days) \& receive IVT 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 Day 7 they will receive targeted pan-retinal photocoagulation (PRP) based on ultra wide field angiography. Ultra wide field angiography will be performed every 3 months to indicate areas of peripheral ischemia, which will be selectively be treated with PRP at Month 6, Month 18, and Month 25, preserving areas of more perfused retina. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- 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
Key exclusion criteria (37 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0.3 mg ranibizumabAlso: LucentisCohort 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, Targeted PRP with 0.3 mg Ranibizumab |
| Targeted Pan Retinal PhotocoagulationAlso: PRP, Laser Photocoagulation, Pan Retinal PhotocoagulationCohort 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 or surgery | Targeted PRP with 0.3 mg Ranibizumab |
Primary outcome
Total Number of Ranibizumab Injections in Each of the Two Cohorts in a 36 Month Period
Time frame: 36 Months
Assess the number of ranibizumab injections in the ranibizumab and targeted panretinal photocoagulation (PRP) with ranibizumab cohorts through Month 36.
Mean Change Over Time in Early Treatment Diabetic Retinopathy Study Best Corrected Visual Acuity (ETDRS BCVA) Through Month 36
Time frame: 36 Months
Evaluate the mean change over time in ETDRS BCVA in the ranibizumab and targeted PRP with ranibizumab cohorts through Month 36.
Incidence and Severity of Ocular and Non-ocular Adverse Events (AE's) Through Month 36.
Time frame: 36 Months
Incidence and severity of ocular and non-ocular adverse events (AE's) in the monotherapy and combination cohorts through Month 36.
5 secondary outcomes
Patients Who Experience a Loss of 15 or More Letters From Baseline to Month 12, 24, and 36 in ETDRS BCVA.
Time frame: Month 12, 24, and 36
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: Month 12, 24, and 36
Evaluate Mean Change in Central Retinal Thickness Over Time Through Month 12, 24, and 36 as Assessed by High Resolution OCT's.
Time frame: Month 12, 24, and 36
Patients With Persistent Macular Edema Post-intravitreal Injection.
Time frame: Month 36
Mean Change in Peripheral Visual Field as Measured by Goldmann Visual Field at Screen and Month and 36.
Time frame: 36 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7487599Klein R, Meuer SM, Moss SE, Klein BE. Retinal microaneurysm counts and 10-year progression of diabetic retinopathy. Arch Ophthalmol. 1995 Nov;113(11):1386-91. doi: 10.1001/archopht.1995.01100110046024.
- Background: PubMed 7643896Klein M. Prevention and treatment of the complications of diabetes mellitus. N Engl J Med. 1995 Sep 21;333(12):802. doi: 10.1056/NEJM199509213331215. No abstract available.
- Background: PubMed 9097744Cruickshanks KJ, Moss SE, Klein R, Klein BE. Physical activity and the risk of progression of retinopathy or the development of proliferative retinopathy. Ophthalmology. 1995 Aug;102(8):1177-82. doi: 10.1016/s0161-6420(95)30893-7.
- Background: PubMed 17698196Diabetic Retinopathy Clinical Research Network; Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK, Elman MJ, Friedman SM, Greven CM, Maturi RK, Pieramici DJ, Shami M, Singerman LJ, Stockdale CR. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology. 2007 Oct;114(10):1860-7. doi: 10.1016/j.ophtha.2007.05.062. Epub 2007 Aug 15.
- Background: PubMed 17420366Writing Committee for the Diabetic Retinopathy Clinical Research Network; Fong DS, Strauber SF, Aiello LP, Beck RW, Callanan DG, Danis RP, Davis MD, Feman SS, Ferris F, Friedman SM, Garcia CA, Glassman AR, Han DP, Le D, Kollman C, Lauer AK, Recchia FM, Solomon SD. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007 Apr;125(4):469-80. doi: 10.1001/archopht.125.4.469.
- Background: PubMed 581885From the NIH: Study identifies four factors in diabetic retinopathy associated with high risk of severe visual loss. JAMA. 1979 Apr 13;241(15):1581. No abstract available.
- Background: PubMed 426679Four risk factors for severe visual loss in diabetic retinopathy. The third report from the Diabetic Retinopathy Study. The Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1979 Apr;97(4):654-5. doi: 10.1001/archopht.1979.01020010310003.
- Background: PubMed 2866759Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806.
- Background: PubMed 3658348Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1987 Jul;94(7):761-74. doi: 10.1016/s0161-6420(87)33527-4.
- Background: PubMed 8111068Muggeo M. DCCT and us: how far are we from implementation? Acta Diabetol. 1993;30(3):115-7. doi: 10.1007/BF00572852. No abstract available.
- Background: PubMed 9889462Luddeke HJ. [Continuing education provided by the Diabetes Society. Results of the UKPDS (United Kingdom Diabetes Society) and therapeutic guidelines concerning diabetes type II]. Fortschr Med. 1998 Nov 30;116(33):35-8. No abstract available. German.
- Background: PubMed 9881303Watkins P. The UKPDS. A model for gathering the evidence for the management of chronic diseases. UK Prospective Diabetes Study Group. J R Coll Physicians Lond. 1998 Nov-Dec;32(6):510-1. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David M Brown, MD principal investigator
Director Greater Houston Research
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 0.3 mg ranibizumab and Targeted Pan Retinal Photocoagulation in people with Diabetic Macular Edema, run by David M. Brown, M.D. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Ranibizumab Injections in Each of the Two Cohorts in a 36 Month Period (time frame: 36 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01552408, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2018.