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

NCT ID: NCT00687804

Last Updated: 2013-04-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

345 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2012-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetic Macular Edema

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Ranibizumab

Intervention Type DRUG

0.5 mg ranibizumab administered by intravitreal injection.

Laser

Intervention Type PROCEDURE

Laser photocoagulation treatment

Sham laser

Intervention Type PROCEDURE

Sham to laser procedure.

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.

Group Type EXPERIMENTAL

Ranibizumab

Intervention Type DRUG

0.5 mg ranibizumab administered by intravitreal injection.

Laser

Intervention Type PROCEDURE

Laser photocoagulation treatment

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.

Group Type ACTIVE_COMPARATOR

Ranibizumab

Intervention Type DRUG

0.5 mg ranibizumab administered by intravitreal injection.

Laser

Intervention Type PROCEDURE

Laser photocoagulation treatment

Sham to ranibizumab

Intervention Type DRUG

Sham to ranibizumab administered as an intravitreal injection.

Interventions

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Ranibizumab

0.5 mg ranibizumab administered by intravitreal injection.

Intervention Type DRUG

Laser

Laser photocoagulation treatment

Intervention Type PROCEDURE

Sham laser

Sham to laser procedure.

Intervention Type PROCEDURE

Sham to ranibizumab

Sham to ranibizumab administered as an intravitreal injection.

Intervention Type DRUG

Eligibility Criteria

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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


-Completion of the Core Study

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Melbourne, , Australia

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Ontario, , Canada

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Düsseldorf, , Germany

Site Status

Novartis Investigative Site

Athens, , Greece

Site Status

Novartis Investigative Site

Budapest, , Hungary

Site Status

Novartis Investigative Site

Florence, , Italy

Site Status

Novartis Investigative Site

Amsterdam, , Netherlands

Site Status

Novartis Investigative Site

Barcelona, , Spain

Site Status

Novartis Investigational Site

Zurich, , Switzerland

Site Status

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Upton, , United Kingdom

Site Status

Countries

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Australia Belgium Canada France Germany Greece Hungary Italy Netherlands Spain Switzerland Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 26584450 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26327116 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25148789 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24491642 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23974915 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21459215 (View on PubMed)

Other Identifiers

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EUDRACT: 2007-004877-24

Identifier Type: -

Identifier Source: secondary_id

CRFB002D2301

Identifier Type: -

Identifier Source: org_study_id

NCT00906464

Identifier Type: -

Identifier Source: nct_alias

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