Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00687804
Registration number
NCT00687804
Ethics application status
Date submitted
27/05/2008
Date registered
2/06/2008
Date last updated
1/04/2013
Titles & IDs
Public title
A 12 Month Core Study to Assess the Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema and a 24 Month Open-label Extension Study
Query!
Scientific title
A Randomized, Double-masked, Multicenter, Laser-controlled Phase III Study Assessing the Efficacy and Safety of Ranibizumab (Intravitreal Injections) as Adjunctive and Mono-therapy in Patients With Visual Impairment Due to Diabetic Macular Edema
Query!
Secondary ID [1]
0
0
EUDRACT: 2007-004877-24
Query!
Secondary ID [2]
0
0
CRFB002D2301
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
RESTORE
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Edema
0
0
Query!
Condition category
Condition code
Eye
0
0
0
0
Query!
Diseases / disorders of the eye
Query!
Cardiovascular
0
0
0
0
Query!
Diseases of the vasculature and circulation including the lymphatic system
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Ranibizumab
Treatment: Surgery - Laser
Treatment: Surgery - Sham laser
Treatment: Drugs - Sham to ranibizumab
Experimental: Ranibizumab 0.5 mg - Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:
Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA \> 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.
Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.
Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.
In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.
Experimental: Ranibizumab 0.5 mg + laser - Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:
Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA \> 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.
Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.
Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.
In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.
Active comparator: Laser - Laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:
Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA \> 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.
Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.
In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.
Treatment: Drugs: Ranibizumab
0.5 mg ranibizumab administered by intravitreal injection.
Treatment: Surgery: Laser
Laser photocoagulation treatment
Treatment: Surgery: Sham laser
Sham to laser procedure.
Treatment: Drugs: Sham to ranibizumab
Sham to ranibizumab administered as an intravitreal injection.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Treatment: Surgery
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Core Study: Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12
Query!
Assessment method [1]
0
0
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Query!
Timepoint [1]
0
0
Baseline through the end of study (Month 12)
Query!
Primary outcome [2]
0
0
Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study
Query!
Assessment method [2]
0
0
Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.
Additional information about adverse events can be found in the Adverse Event section.
Query!
Timepoint [2]
0
0
Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Query!
Primary outcome [3]
0
0
Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study
Query!
Assessment method [3]
0
0
Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.
Additional information about adverse events can be found in the Adverse Event section.
Query!
Timepoint [3]
0
0
Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Query!
Secondary outcome [1]
0
0
Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
Query!
Assessment method [1]
0
0
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Query!
Timepoint [1]
0
0
Baseline to Month 12
Query!
Secondary outcome [2]
0
0
Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time
Query!
Assessment method [2]
0
0
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Query!
Timepoint [2]
0
0
Baseline to Month 12
Query!
Secondary outcome [3]
0
0
Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye
Query!
Assessment method [3]
0
0
Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation.
Query!
Timepoint [3]
0
0
Baseline to Month 12
Query!
Secondary outcome [4]
0
0
Core Study: Mean Change From Baseline in Patient-reported Visual Functioning
Query!
Assessment method [4]
0
0
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure a patient's subjective assessment of vision-related quality of life. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.
Query!
Timepoint [4]
0
0
Baseline to Month 12
Query!
Secondary outcome [5]
0
0
Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies
Query!
Assessment method [5]
0
0
Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.
Additional information about adverse events can be found in the Adverse Event section.
Query!
Timepoint [5]
0
0
Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
Query!
Secondary outcome [6]
0
0
Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies
Query!
Assessment method [6]
0
0
Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.
Additional information about Adverse Events can be found in the Adverse Event section.
Query!
Timepoint [6]
0
0
Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
Query!
Secondary outcome [7]
0
0
Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Query!
Assessment method [7]
0
0
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. An increase in the number of letters read correctly indicates improvement.
Query!
Timepoint [7]
0
0
Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
Query!
Secondary outcome [8]
0
0
Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Query!
Assessment method [8]
0
0
Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. An increase in the number of letters read correctly indicates improvement.
Query!
Timepoint [8]
0
0
Core baseline (Day 1 of the core study), Month 36 (end of extension study)
Query!
Eligibility
Key inclusion criteria
* Visual acuity impairment
* Diabetic macular edema in at least one eye
* Type 1 or type 2 diabetes mellitus
* Medication for the diabetes treatment must be stable for the last 3 months
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Patients with uncontrolled systemic or ocular diseases
* Laser photocoagulation in the study eye for the last 3 months
* Any history of any intraocular surgery in the study eye within the past 3 months
* Blood pressure > 160/100 mmHg
Extension Inclusion Criteria:
-Completion of the Core Study
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/05/2008
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/01/2012
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
345
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
- Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
Belgium
Query!
State/province [1]
0
0
Leuven
Query!
Country [2]
0
0
Canada
Query!
State/province [2]
0
0
Ontario
Query!
Country [3]
0
0
France
Query!
State/province [3]
0
0
Paris
Query!
Country [4]
0
0
Germany
Query!
State/province [4]
0
0
Düsseldorf
Query!
Country [5]
0
0
Greece
Query!
State/province [5]
0
0
Athens
Query!
Country [6]
0
0
Hungary
Query!
State/province [6]
0
0
Budapest
Query!
Country [7]
0
0
Italy
Query!
State/province [7]
0
0
Firenze
Query!
Country [8]
0
0
Netherlands
Query!
State/province [8]
0
0
Amsterdam
Query!
Country [9]
0
0
Spain
Query!
State/province [9]
0
0
Barcelona
Query!
Country [10]
0
0
Switzerland
Query!
State/province [10]
0
0
Zurich
Query!
Country [11]
0
0
Turkey
Query!
State/province [11]
0
0
Ankara
Query!
Country [12]
0
0
United Kingdom
Query!
State/province [12]
0
0
Upton
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Novartis
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
CRFB002D2301: The core study was designed to confirm the efficacy and safety of ranibizumab (0.5 mg) as adjunctive therapy when added to laser photocoagulation and/or mono-therapy in patients with visual impairment due to diabetic macular edema. CRFB002D2301E1: A 24 month open-label extension study for participants who completed the 12 month core study evaluated the long-term safety and efficacy of ranibizumab (0.5 mg) as symptomatic treatment for visual impairment due to diabetic macular edema.
Query!
Trial website
https://clinicaltrials.gov/study/NCT00687804
Query!
Trial related presentations / publications
Bressler NM, Varma R, Mitchell P, Suner IJ, Dolan C, Ward J, Ferreira A, Ehrlich JS, Turpcu A. Effect of Ranibizumab on the Decision to Drive and Vision Function Relevant to Driving in Patients With Diabetic Macular Edema: Report From RESTORE, RIDE, and RISE Trials. JAMA Ophthalmol. 2016 Feb;134(2):160-6. doi: 10.1001/jamaophthalmol.2015.4636. Mitchell P, Massin P, Bressler S, Coon CD, Petrillo J, Ferreira A, Bressler NM. Three-year patient-reported visual function outcomes in diabetic macular edema managed with ranibizumab: the RESTORE extension study. Curr Med Res Opin. 2015 Nov;31(11):1967-75. doi: 10.1185/03007995.2015.1081880. Epub 2015 Oct 6. Bressler NM, Varma R, Suner IJ, Dolan CM, Ward J, Ehrlich JS, Colman S, Turpcu A; RIDE and RISE Research Groups. Vision-related function after ranibizumab treatment for diabetic macular edema: results from RIDE and RISE. Ophthalmology. 2014 Dec;121(12):2461-72. doi: 10.1016/j.ophtha.2014.07.008. Epub 2014 Aug 20. Mitchell P, Bressler N, Tolley K, Gallagher M, Petrillo J, Ferreira A, Wood R, Bandello F; RESTORE Study Group. Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial. JAMA Ophthalmol. 2013 Oct;131(10):1339-47. doi: 10.1001/jamaophthalmol.2013.4592. Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031. Schmidt-Erfurth U, Lang GE, Holz FG, Schlingemann RO, Lanzetta P, Massin P, Gerstner O, Bouazza AS, Shen H, Osborne A, Mitchell P; RESTORE Extension Study Group. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014 May;121(5):1045-53. doi: 10.1016/j.ophtha.2013.11.041. Epub 2014 Feb 1.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT00687804
Download to PDF