Aflibercept anD navigateD vErsus coNvensional Laser in Diabetic macUlar edeMa

NCT02554747 | Completed DMC

• 2 other identifiers: SDUSF-2015-21-(129)S-20150077
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic macular edema (DME) in diabetic retinopathy (DR) is the leading cause of visual impairment among the 300,000 Danish patients with diabetes (DM) and will in time affect 29% of patients. Because of DME, 550 intravitreal injections were given at Odense University Hospital in 2014 with medicine expenses approximating 3.3 million DKK. With an increasing prevalence of diabetes, the number is expected to rise significantly for the years to come. The investigators hypothesize that combination therapy with intravitreal aflibercept and a new computer navigated photocoagulations system (Navilas®) leads to a decreased need for intravitreal injections. Further, the investigators wish to identify retinal risk markers for DME treatment outcome to assist individualized treatment planning. The evaluation of the baseline level of macular ischemia as marker of successful treatment outcome is of particular interest as this is still highly debatable and may prove a significant prognostic factor of anatomical and functional outcome to anti-VEGF treatment. The ADDENDUM study (four-year part-time PhD study) is a 12-month prospective randomized 1:1 study to compare intravitreal aflibercept and Navilas® laser (Group A) with intravitreal aflibercept and conventional Pascal laser (Group B) in the treatment of DME. Eligibility criteria: DM, age 18-99, clinically significant macular edema, central retinal thickness \> 300 μm, best corrected visual acuity 35-75 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. The investigators believe that this study holds the potential to set precedent for a new gold standard of DME-treatment with increased treatment effect, reduced risks and a more cost-effective approach.

Conditions

Diabetic Macular Oedema

Outcome Measures

Primary Outcomes (1)

• Percentage of eyes that received additional aflibercept injections after laser at month 12 in group A and B

  1 year

Secondary Outcomes (9)

• Number of additional aflibercept injections after laser at month 12 in group A and B

  1 year

• Change in ETDRS visual acuity from baseline to month 12 in group A and B

  1 year

• Change in global retinal vessel geometric markers from baseline to month 12 in group A and B

  1 year

• Change in macular retinal vessel geometric markers from baseline to month 12 in group A and B

  1 year

• Change in global oxygen saturation from baseline to month 12 in group A and B

  1 year

Study Arms (2)

Navigated laser

EXPERIMENTAL

Aflibercept, Navilas®

Device: Navigated laser

Conventional laser

ACTIVE COMPARATOR

Aflibercept, Pascal

Device: Conventional laser

Interventions

Navigated laser DEVICE

Aflibercept, Navilas®

Navigated laser

Conventional laser DEVICE

Aflibercept, Pascal

Conventional laser

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diabetes mellitus
• Clinically significant macular edema in the study eye.
• Central retinal thickness \> 300 μm in the study eye.
• Best corrected visual acuity 35-80 ETDRS letters (0.10-0.80 Snellen equivalent) in the study eye.

You may not qualify if:

• Pregnancy.
• Active proliferative diabetic retinopathy in the study eye.
• History of cataract surgery, YAG capsulotomy, vitrectomy or retinal laser treatment in the study eye within 4 months prior to randomization.
• Ocular condition(s) in the study eye that in the opinion of the investigator would prevent improvement of visual acuity.

Sponsors & Collaborators

• Odense University Hospital: lead
• Moorfields Eye Hospital NHS Foundation Trust: collaborator

Study Sites (1)

Research Unit of Ophthalmology, Clinical Institute, University of Southern Denmark, Department of Ophthalmology, Odense University Hospital.

Odense, Fyn, 5000, Denmark

Location

Related Publications (17)

• Grauslund J, Green A, Sjolie AK. Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients. Diabetologia. 2009 Sep;52(9):1829-35. doi: 10.1007/s00125-009-1450-4. Epub 2009 Jul 12.

  PMID: 19593541 BACKGROUND

• Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology. 2009 Mar;116(3):497-503. doi: 10.1016/j.ophtha.2008.10.016. Epub 2009 Jan 22.

  PMID: 19167079 BACKGROUND

• Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766-85.

  PMID: 2062512 BACKGROUND

• Rajendram R, Fraser-Bell S, Kaines A, Michaelides M, Hamilton RD, Esposti SD, Peto T, Egan C, Bunce C, Leslie RD, Hykin PG. A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol. 2012 Aug;130(8):972-9. doi: 10.1001/archophthalmol.2012.393.

  PMID: 22491395 BACKGROUND

• Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

  PMID: 20427088 BACKGROUND

• Do DV, Nguyen QD, Boyer D, Schmidt-Erfurth U, Brown DM, Vitti R, Berliner AJ, Gao B, Zeitz O, Ruckert R, Schmelter T, Sandbrink R, Heier JS; da Vinci Study Group. One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012 Aug;119(8):1658-65. doi: 10.1016/j.ophtha.2012.02.010. Epub 2012 Apr 24.

  PMID: 22537617 BACKGROUND

• Neubauer AS, Langer J, Liegl R, Haritoglou C, Wolf A, Kozak I, Seidensticker F, Ulbig M, Freeman WR, Kampik A, Kernt M. Navigated macular laser decreases retreatment rate for diabetic macular edema: a comparison with conventional macular laser. Clin Ophthalmol. 2013;7:121-8. doi: 10.2147/OPTH.S38559. Epub 2013 Jan 16.

  PMID: 23345966 BACKGROUND

• Barteselli G, Kozak I, El-Emam S, Chhablani J, Cortes MA, Freeman WR. 12-month results of the standardised combination therapy for diabetic macular oedema: intravitreal bevacizumab and navigated retinal photocoagulation. Br J Ophthalmol. 2014 Aug;98(8):1036-41. doi: 10.1136/bjophthalmol-2013-304488. Epub 2014 Apr 10.

  PMID: 24723616 BACKGROUND

• Liegl R, Langer J, Seidensticker F, Reznicek L, Haritoglou C, Ulbig MW, Neubauer AS, Kampik A, Kernt M. Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema. PLoS One. 2014 Dec 26;9(12):e113981. doi: 10.1371/journal.pone.0113981. eCollection 2014.

  PMID: 25541960 BACKGROUND

• Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.

  PMID: 25692915 BACKGROUND

• Broe R, Rasmussen ML, Frydkjaer-Olsen U, Olsen BS, Mortensen HB, Hodgson L, Wong TY, Peto T, Grauslund J. Retinal vessel calibers predict long-term microvascular complications in type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987). Diabetes. 2014 Nov;63(11):3906-14. doi: 10.2337/db14-0227. Epub 2014 Jun 9.

  PMID: 24914239 BACKGROUND

• Broe R, Rasmussen ML, Frydkjaer-Olsen U, Olsen BS, Mortensen HB, Peto T, Grauslund J. Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987). Diabetologia. 2014 Oct;57(10):2215-21. doi: 10.1007/s00125-014-3317-6. Epub 2014 Jul 1.

  PMID: 24981770 BACKGROUND

• Lundberg K, Kawasaki R, Sjolie AK, Wong TY, Grauslund J. Localized changes in retinal vessel caliber after focal/grid laser treatment in patients with diabetic macular edema: a measure of treatment response? Retina. 2013 Nov-Dec;33(10):2089-95. doi: 10.1097/IAE.0b013e3182891dda.

  PMID: 23514802 BACKGROUND

• Jorgensen CM, Hardarson SH, Bek T. The oxygen saturation in retinal vessels from diabetic patients depends on the severity and type of vision-threatening retinopathy. Acta Ophthalmol. 2014 Feb;92(1):34-9. doi: 10.1111/aos.12283. Epub 2013 Dec 16.

  PMID: 24330421 BACKGROUND

• Neubauer AS, Kook D, Haritoglou C, Priglinger SG, Kampik A, Ulbig MW, Ceklic L. Bevacizumab and retinal ischemia. Ophthalmology. 2007 Nov;114(11):2096. doi: 10.1016/j.ophtha.2007.05.057. No abstract available.

  PMID: 17980746 BACKGROUND

• Douvali M, Chatziralli IP, Theodossiadis PG, Chatzistefanou KI, Giannakaki E, Rouvas AA. Effect of macular ischemia on intravitreal ranibizumab treatment for diabetic macular edema. Ophthalmologica. 2014;232(3):136-43. doi: 10.1159/000360909. Epub 2014 Aug 27.

  PMID: 25171753 BACKGROUND

• Blindbaek SL, Peto T, Grauslund J. Retinal arteriolar oxygen saturation predicts the need for intravitreal aflibercept in patients with diabetic macular oedema. BMJ Open Ophthalmol. 2020 May 27;5(1):e000382. doi: 10.1136/bmjophth-2019-000382. eCollection 2020.

  PMID: 32524033 DERIVED

Study Officials

• Søren Leer Blindbæk, MD

  Research Unit of Ophthalmology, Clinical Institute, University of Southern Denmark and Department of Ophthalmology, Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 11, 2015
• First Posted: September 18, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: November 1, 2018
• Last Updated: March 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)