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Influence of Diabetes Control on Treatment of Diabetic Macular Edema With Ranibizumab (DORO)

Primary Purpose

Visual Acuity Reduced Transiently, Macular Edema, Cystoid

Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
ranibizumab
Sponsored by
Prof. Dr. Antonia M. Joussen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Visual Acuity Reduced Transiently focused on measuring Diabetic Macular Edema, Ranibizumab, Visual Acuity, Diabetic Control

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- Patients with diabetic macular edema relevant to visual acuity

  • OCT central retinal thickness ≥ 250µm
  • HbA1c > 6,5% at initial visit
  • BCVA ≤0.8 and ≥0.05
  • Age ≥18 years
  • Written patient informed consent given

Exclusion Criteria:

  • Previous treatment with intravitreal drugs in last 6 months
  • Vitreous hemorrhage as a consequence of proliferative retinopathy
  • Pregnancy
  • Blood pressure of ≥ 180/100 (or uncontrolled pressures under pharmacological therapy)
  • Chronic systemic or ocular inflammatory/autoimmune diseases (e.g. inflammatory bowel disease, Addison´s disease, Cushing Syndrome, Uveitis)
  • Systemic cortisone or anti-VEGF therapy
  • Acute systemic or ocular infectious diseases

Sites / Locations

  • Department of Ophthalmology, Charite, Berlin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Regular Glycemic Control

Intensified Glycemic Control

Arm Description

Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control.

Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake.

Outcomes

Primary Outcome Measures

Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 12 Baseline Visit
Measured by the difference in ETDRS letters score between month 12 and baseline according to internal guideline of Charité department of ophthalmology.

Secondary Outcome Measures

Number of Treatments With Ranibizumab up to 6, 12, 18 and 24 Months of Treatment
For the number of treatments at 6, 12, 18 and 24 months, an ANOVA without any covariates was planned to be applied at each endpoint 6, 12, 18 and 24 months. As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus statistical analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12. Results are only shown descriptively. Ranibizumab injections were summed up per study arm as well as cumulative at each time point.
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit
As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. Time point 24 months was reached by none of the patients due to trial discontinuation. Results are only shown descriptively. Best-corrected visual acuity (BCVA) score is shown as change in ETDRS letters score at the distinct time point compared to baseline. Higher scores mean a better outcome.
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline
As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12 due to trial discontinuation. Results are only shown descriptively. Macular thickness (study eye) is shown as change in thickness [µm] compared to individual baseline value. A reduction in thickness means improvement.
Time to Reach Target HbA1c
Number of Panretinal Laser Photocoagulation (PRP) Treatments Necessary for Neovascular Complications
Need for PRP is up to the investigator's decision. Assessment was done on every visit. Intended time frame was baseline to 24 months. None of the patients reached time points beyond month 12 due to study discontinuation. Unit of measure is any separate investigator's decision to perform panretinal laser photocoagulation (PRP) for neovascular complications. Each PRP is counted separately.
Number of Participants With Retinal Detachment, Central Retinal Artery Occlusion, or Endophthalmitis and/or Ocular Adverse Events That Are Related to Treatment
All ocular adverse events presented from baseline to 24 months will be documented.
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
All adverse events were documented. Causal relationship to study treatment was assessed by the investigators. Intended time frame was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.

Full Information

First Posted
January 21, 2016
Last Updated
October 31, 2019
Sponsor
Prof. Dr. Antonia M. Joussen
Collaborators
Charite University, Berlin, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT02665689
Brief Title
Influence of Diabetes Control on Treatment of Diabetic Macular Edema With Ranibizumab
Acronym
DORO
Official Title
Influence of Diabetes Control on Treatment of Diabetic Macular Edema With Ranibizumab
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Why Stopped
Enrollment pace was far below target.
Study Start Date
January 18, 2016 (Actual)
Primary Completion Date
September 7, 2018 (Actual)
Study Completion Date
September 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Dr. Antonia M. Joussen
Collaborators
Charite University, Berlin, Germany

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of the prospective randomized study is to investigate whether a intensified diabetic control program leads to better final visual acuity and less frequent diabetic ocular complications in patients with diabetic retinopathy when compared with a normal diabetic treatment.
Detailed Description
Patients with diabetic macular edema (DME) will be treated with intravitreal ranibizumab injections and the effect of optimal control of internal factors (eg. glycemia, blood pressure etc) on final functional (best corrected visual acuity-CBVA) and morphological (central retinal thickness-CRT) will be investigated. Patients will be randomized into two groups: Group with intensified diabetic control will be follow and investigated monthly at department of diabetology, endocrinology and nutritional medicine (Campus Benjamin Franklin) in Berlin with aim to reach the optimal glycemic control defined as HbA1c < 6,5%. Further, triglycerides values < 140 mg/dl and blood pressure < 140/90 mmHg will be pursued. Second group of patients will be followed by their general practitioner and in the study center only blood samples will be taken quarterly without active medical intervention. BCVA, CRT and the number of required ranibizumab injections will we evaluated and compared between both study groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Visual Acuity Reduced Transiently, Macular Edema, Cystoid
Keywords
Diabetic Macular Edema, Ranibizumab, Visual Acuity, Diabetic Control

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Observer-masking (assessment of BCVA, macular thickness, capillary drop-out) is done to guard against detection bias.
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regular Glycemic Control
Arm Type
Active Comparator
Arm Description
Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control.
Arm Title
Intensified Glycemic Control
Arm Type
Experimental
Arm Description
Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake.
Intervention Type
Drug
Intervention Name(s)
ranibizumab
Intervention Description
Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Primary Outcome Measure Information:
Title
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 12 Baseline Visit
Description
Measured by the difference in ETDRS letters score between month 12 and baseline according to internal guideline of Charité department of ophthalmology.
Time Frame
Baseline to 12 months
Secondary Outcome Measure Information:
Title
Number of Treatments With Ranibizumab up to 6, 12, 18 and 24 Months of Treatment
Description
For the number of treatments at 6, 12, 18 and 24 months, an ANOVA without any covariates was planned to be applied at each endpoint 6, 12, 18 and 24 months. As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus statistical analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12. Results are only shown descriptively. Ranibizumab injections were summed up per study arm as well as cumulative at each time point.
Time Frame
Baseline to 12 months
Title
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit
Description
As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. Time point 24 months was reached by none of the patients due to trial discontinuation. Results are only shown descriptively. Best-corrected visual acuity (BCVA) score is shown as change in ETDRS letters score at the distinct time point compared to baseline. Higher scores mean a better outcome.
Time Frame
Baseline to 12 months
Title
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline
Description
As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12 due to trial discontinuation. Results are only shown descriptively. Macular thickness (study eye) is shown as change in thickness [µm] compared to individual baseline value. A reduction in thickness means improvement.
Time Frame
Baseline to 12 months
Title
Time to Reach Target HbA1c
Time Frame
24 months
Title
Number of Panretinal Laser Photocoagulation (PRP) Treatments Necessary for Neovascular Complications
Description
Need for PRP is up to the investigator's decision. Assessment was done on every visit. Intended time frame was baseline to 24 months. None of the patients reached time points beyond month 12 due to study discontinuation. Unit of measure is any separate investigator's decision to perform panretinal laser photocoagulation (PRP) for neovascular complications. Each PRP is counted separately.
Time Frame
Baseline to 12 months
Title
Number of Participants With Retinal Detachment, Central Retinal Artery Occlusion, or Endophthalmitis and/or Ocular Adverse Events That Are Related to Treatment
Description
All ocular adverse events presented from baseline to 24 months will be documented.
Time Frame
Baseline to 12 months
Title
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Description
All adverse events were documented. Causal relationship to study treatment was assessed by the investigators. Intended time frame was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Time Frame
Baseline to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Patients with diabetic macular edema relevant to visual acuity OCT central retinal thickness ≥ 250µm HbA1c > 6,5% at initial visit BCVA ≤0.8 and ≥0.05 Age ≥18 years Written patient informed consent given Exclusion Criteria: Previous treatment with intravitreal drugs in last 6 months Vitreous hemorrhage as a consequence of proliferative retinopathy Pregnancy Blood pressure of ≥ 180/100 (or uncontrolled pressures under pharmacological therapy) Chronic systemic or ocular inflammatory/autoimmune diseases (e.g. inflammatory bowel disease, Addison´s disease, Cushing Syndrome, Uveitis) Systemic cortisone or anti-VEGF therapy Acute systemic or ocular infectious diseases
Facility Information:
Facility Name
Department of Ophthalmology, Charite, Berlin
City
Berlin
ZIP/Postal Code
12203
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

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Influence of Diabetes Control on Treatment of Diabetic Macular Edema With Ranibizumab

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